Advanced Solid TumorsPhase 1NCT03799003
A Study of ASP1951 in Subjects With Advanced Solid Tumors
A Phase 1 study testing ASP1951 and pembrolizumab in people with Advanced Solid Tumors, run by Astellas Pharma Global Development, Inc. at 32 sites in 4 countries.
Trial summary
The primary purpose of this study is to evaluate the tolerability and safety profile of ASP1951 when administered as a single agent and in combination with pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1951 when… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- ASP1951 and pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 32 sitesin 4 countries
- Study dates
- 14 Jan 2019to 6 Jul 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy as well as the following:
- Subject in the escalation cohort has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit the subject's specific tumor type. OR
- Subject in an expansion cohort has received at least 1 standard therapy for the subject's specific tumor type.
- [Taiwan only]: Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy and has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit in the opinion of the treating investigator for his/her specific tumor type. Note: Subjects in the combination expansion cohort with tumor types that pembrolizumab is not approved for can only enroll if their standard treatment is ineffective, unsuitable per investigator's judgment or if the subject is unwilling to receive the standard therapy.
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5-half-lives, whichever is shorter, prior to initiation of study drug administration. A subject with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor therapy until 4 days prior to the start of study drug administration.
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- Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 2 weeks prior to study drug administration. Subjects must have recovered from all radiation related toxicities, not require corticosteroids and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to noncentral nervous system [CNS] disease.
- Subject's AEs (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 2 weeks prior to start of study treatment.
- Subject with metastatic castration-resistant prostate cancer (mCRPC) (positive bone scan and/or soft tissue disease documented by computed tomography [CT]/magnetic resonance imaging [MRI]) meets both of the following:
- Subject has serum testosterone ≤ 50 ng/dL at Screening.
- Subject has had a bilateral orchiectomy or plans to continue androgen deprivation therapy (ADT) for the duration of study treatment.
- Subject has adequate organ function prior to start of study treatment. If a subject has received a recent blood transfusion, the laboratory tests must be obtained ≥ 4 weeks after any blood transfusion. Subjects can be on stable dose of erythropoietin (≥ approximately 3 months).
- A female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP); OR
- WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final study drug administration.
- Female subject must agree not to breastfeed starting at Screening and throughout the study treatment, and for 6 months after the final study drug administration.
- Female subject must not donate ova starting at Screening and throughout the study treatment, and for 6 months after the final study drug administration.
- A male subject with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 6 months after the final study drug administration.
- A male subject must not donate sperm during the treatment period and for at least 6 months after the final study drug administration.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 6 months after the final study drug administration.
- Subject agrees not to participate in another interventional study while receiving study drug (Subjects who are currently in the follow-up period of an interventional clinical trial are allowed).
- Additional Inclusion Criteria for Subjects in the Expansion Cohorts:
- Subject has at least 1 measureable lesion per RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Subjects with mC RPC who do not have measurable lesions must have at least 1 of the following:
- Progression with 2 or more new bone lesions; or
- Prostate-specific antigen (PSA) progression (defined as a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination) within 6 weeks prior to study drug administration and a PSA value at the screening visit ≥ 2 ng/mL.
- Subject consents to provide available tumor specimen in a tissue block or unstained serial slides obtained within 56 days prior to first dose of study treatment. Note: This does not apply to subjects with mCRPC who do not have measurable disease.
- Subject is an appropriate candidate for tumor biopsy and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period as indicated in the Schedule of Assessments. Note: This does not apply to subjects with mCRPC who do not have measurable disease.
- Subject meets one of the following:
- Subject has the tumor type for which a confirmed response was observed in a monotherapy or combination therapy cohort; or
- Subject has SCCHN and a combination therapy expansion cohort is opened due to achieving the predicted efficacious exposure or
- High dose RP2D combination therapy expansion cohorts are opened and subject has NSCLC (all PD-L1 status), NSCLC PD-L1 high*, SCCHN, or cervical cancer; or
- Low dose RP2D combination therapy expansion cohorts are opened and subject has NSCLC (all PD-L1 status), SCCHN and cervical cancer.
- NSCLC with PD-L1 high expressing tumor (tumor proportion score ≥ 50%) as determined by 22C3 PD-L1 immunohistochemistry assay at a local/central laboratory during the screening period. Note: Local 22C3 PD-L1 IHC assay results available within 60 days prior study drug administration may be used for evaluating this entry criterion.
- Additional Inclusion Criteria for Re-treatment:
- Subject stopped initial treatment with ASP1951 or ASP1951 in combination with pembrolizumab after attaining a confirmed CR, PR or SD.
- Subject experienced an investigator-determined iCPD after stopping their initial treatment with ASP1951 or ASP1951 in combination with pembrolizumab.
- Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1951 or ASP1951 in combination with pembrolizumab.
- Subject did not experience a toxicity that met treatment discontinuation criteria during the initial treatment with ASP1951 or ASP1951 in combination with pembrolizumab or pembrolizumab alone.
Who cannot join
- Subject weighs < 45 kg.
- Subject has received investigational therapy (other than an investigational EGFR TKI in a subject with EGFR activating mutations or ALK inhibitor in a subject with an ALK mutation) within 21 days or 5-half-lives, whichever is shorter, prior to start of study drug.
- Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study drug administration. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone) are allowed.
- Subject has symptomatic CNS metastases or subject has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Subjects with previously treated CNS metastases are eligible, if they are clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone, > 2 mg per day of dexamethasone, or > 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
- Subject has leptomeningeal disease as a manifestation of the current malignancy.
- Subject has an active autoimmune disease that has required systemic treatment in the past 2 years. Subjects with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, and skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed.
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- Subject was discontinued from prior immunomodulatory therapy due to a grade ≥ 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
- Subject has known history of serious hypersensitivity reaction (≥ grade 3) to a known ingredient of ASP1951 or pembrolizumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
- Subject with positive Hepatitis B virus (HBV) antibodies and surface antigen (indicating acute HBV or chronic HBV) or Hepatitis C ([HCV]; ribonucleic acid [RNA] detected by qualitative or quantitative assay). Hepatitis C RNA testing is not required in subjects with negative Hepatitis C antibody testing. HBV antibodies are not required in subjects with negative HBV surface antigen.
- Subject has received a live vaccine against infectious diseases within 4 weeks prior to initiation of study treatment.
- Subject has a history of drug-induced pneumonitis (interstitial lung disease), a history of (non-infectious) pneumonitis that required steroids, radiation pneumonitis or currently has pneumonitis.
- Subject has an infection requiring systemic therapy within 2 weeks prior to study drug administration.
- Subject has received a prior allogeneic bone marrow or solid organ transplant.
- Subject is expected to require another form of antineoplastic therapy while on study treatment.
- Subject has had a myocardial infarction or unstable angina within 6 months prior to the start of study treatment or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Subject has received prior treatment with an anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) antibody.
- Subject has had a major surgical procedure and has not completely recovered within 28 days prior to the start of study treatment.
- Subject has any condition which makes the subject unsuitable for study participation.
- Subject has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
- Subject has known history of coronavirus disease 2019 (COVID-19) positive polymerase chain reaction (PCR) test within 4 weeks prior to start of study treatment.
- Additional Exclusion Criterion for Subjects in Expansion Cohorts:
- Subject has a prior malignancy, other than the current malignancy for which the subject is seeking treatment, active (i.e., requiring treatment of intervention) within the previous 2 years except for locally curable malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- Additional Exclusion Criteria for Re-treatment:
- Subjects who have completed 45 weeks in monotherapy or 57 weeks in combination therapy follow-up with disease control are not eligible for re-treatment.
- Subject currently has an ongoing AE related to ASP1951 or ASP1951 in combination with pembrolizumab that meets the criteria for treatment interruption or discontinuation.
Trial locations and contacts
32 sites in 4 countries.
32 sites in 4 countries
United States20 sites
Emory University
Atlanta, Georgia, 30322
Augusta University
Augusta, Georgia, 30912
Hollings Cancer Center
Charleston, South Carolina, 29425
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
Henry Ford Health System
Detroit, Michigan, 48202
Duke University Medical Center
Durham, North Carolina, 27705
Virginia Cancer Specialists
Fairfax, Virginia, 22031
University of Florida, Davis C
Gainesville, Florida, 326102
University of Iowa Hospitals
Iowa City, Iowa, 52242
Comprehensive Cancer Nevada
Las Vegas, Nevada, 89169
Rutgers Cancer Institute
New Brunswick, New Jersey, 08903
Icahn school of Medicine at Mount Sinai
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
University of California
Sacramento, California, 95817
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
Multicare Regional Cancer Center Tacoma
Tacoma, Washington, 98405
Arizona Clinical Research Cent
Tucson, Arizona, 85715
South Korea7 sites
Site KR82002
Chungcheongbukdo
Site KR82005
Daegu
Site KR82001
Gyeonggi-do
Site KR82003
Seoul
Site KR82004
Seoul
Site KR82006
Seoul
Site KR82007
Seoul
About this study
Official title: A Phase 1b Study of ASP1951, a GITR Agonistic Antibody, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
The primary purpose of this study is to evaluate the tolerability and safety profile of ASP1951 when administered as a single agent and in combination with pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1951 when administered as a single agent and in combination with pembrolizumab; and determine the recommended phase 2 dose (RP2D) of ASP1951 and/or maximum tolerated dose (MTD) when administered as a single agent and in combination with pembrolizumab. This study will also evaluate the anti-tumor effect of ASP1951 when administered as a single agent and in combination with pembrolizumab.
Read the detailed description
This is a dose-escalation and expansion study of ASP1951. The study consists of 3 periods for monotherapy and combination therapy: screening, treatment and follow up, followed by an optional Re-treatment period for participants that qualify.
The monotherapy escalation cohorts will evaluate escalating dose levels of ASP1951 in participants with locally advanced (unresectable) or metastatic solid tumor malignancies including but not limited to squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer, metastatic castration-resistant prostate cancer (mCRPC) and cervical cancer.
The combination escalation cohorts will evaluate escalating dose levels of ASP1951 in combination with a fixed dose of pembrolizumab.
For dose expansion, the tumor-specific cohorts will include participants with squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC) (all PD-L1 status), NSCLC PDL1 high, and cervical cancer, as well as participants with any tumor types that respond to study drug treatment during dose escalation.
Participants may reinitiate study drug treatment in the optional Re-treatment period after confirmation that the participant meets all the re-treatment eligibility criteria.
After discontinuation of study drug, all participants will complete an end-of-treatment visit, along with 30-day and 90 day safety follow-up visits from the last dose of study drug.
- Conditions
- Advanced Solid Tumors
- Being tested
- ASP1951, pembrolizumab
- Keywords
- ASP1951, cervical cancer, Oncology, squamous cell carcinoma of the head and neck (SCCHN), metastatic castration-resistant prostate cancer (mCRPC), melanoma, Tumors, pembrolizumab, colorectal cancer, Advanced (unresectable) or metastatic solid tumor malignancies, Advanced solid tumors
- Medical subject headings
- Uterine Cervical Neoplasms, Neoplasms, Squamous Cell Carcinoma of Head and Neck, Melanoma, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASP1951Drug
Intravenously (IV)
pembrolizumabDrug
Also called KEYTRUDA®
Intravenously (IV)
| Study group | Role | What they receive |
|---|---|---|
| ASP1951 0.07 mg Monotherapy | Experimental | Participants have received ASP1951 0.07 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 0.7 mg Monotherapy | Experimental | Participants have received ASP1951 0.7 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 5 mg Monotherapy | Experimental | Participants have received ASP1951 5 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 20 mg Monotherapy | Experimental | Participants have received ASP1951 20 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 70 mg Monotherapy | Experimental | Participants have received ASP1951 70 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 200 mg Monotherapy | Experimental | Participants have received ASP1951 200 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 700 mg Monotherapy | Experimental | Participants have received ASP1951 700 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 1400 mg Monotherapy | Experimental | Participants have received ASP1951 1400 mg intravenously on day 1 of every 3-week cycle. Receives: Drug: ASP1951 |
| ASP1951 20 mg + pembrolizumab 200 mg Combination Therapy | Experimental | Participants have received ASP1951 20 mg intravenously on day 1 of every 3-week cycle in combination with pembrolizumab 200 mg administered on day 1 of every 3-week cycle, at least 30 minutes after the end of infusion of ASP1951. Receives: Drug: ASP1951; Drug: pembrolizumab |
| ASP1951 700 mg + pembrolizumab 200 mg Combination Therapy | Experimental | Participants have received ASP1951 700 mg intravenously on day 1 of every 3-week cycle in combination with pembrolizumab 200 mg administered on day 1 of every 3-week cycle, at least 30 minutes after the end of infusion of ASP1951. Receives: Drug: ASP1951; Drug: pembrolizumab |
| ASP1951 1400 mg + pembrolizumab 200 mg Combination Therapy | Experimental | Participants have received ASP1951 1400 mg intravenously on day 1 of every 3-week cycle in combination with pembrolizumab 200 mg administered on day 1 of every 3-week cycle, at least 30 minutes after the end of infusion of ASP1951. Receives: Drug: ASP1951; Drug: pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability assessed by Dose Limiting Toxicity (DLT)
A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 4.03) that the investigator (or sponsor) cannot clearly attribute to a cause other than study drug.
Measured: Up to 5 years
Safety and tolerability assessed by adverse events (AEs)
Initial and retreatment. An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. AEs will be coded using the medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE 4.03.
Measured: Up to 5 years
Safety and tolerability assessed by immune-related AEs (irAEs)
Initial and retreatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies (hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency and Type 1 diabetes mellitus). In the event a participant is diagnosed with an irAE, then it should be reported as an AE.
Measured: Up to 5 years
Safety and tolerability assessed by infusion-related reactions (IRRs)
Initial and retreatment. IRRs are considered AEs of special interest. In the event a participant is diagnosed with an IRR, then it should be reported as an AE.
Measured: Up to 5 years
Safety and tolerability assessed by serious adverse events (SAEs)
Initial and retreatment. An AE is considered "serious" if it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE). Hospitalization for treatment/observation/examination caused by AE is to be considered as serious; and other medically important events.
Measured: Up to 5 years
Number of participants with laboratory value abnormalities and/or adverse events related to treatment
Initial and retreatment. Number of participants with potentially clinically significant laboratory values.
Measured: Up to 5 years
Safety and tolerability assessed by 12- lead electrocardiogram (ECG)
Initial and retreatment. ECGs should be obtained after the participant has rested in supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.
Measured: Up to 5 years
Number of participants with vital signs abnormalities and/or adverse events related to treatment
Initial and retreatment. Number of participants with potentially clinically significant vital sign values.
Measured: Up to 5 years
Number of participants with Physical Exam abnormalities and/or adverse events related to treatment
Initial and retreatment. Number of participants with potentially clinically significant physical exam values.
Measured: Up to 5 years
Safety and tolerability assessed by ECOG performance status
Initial and retreatment. The Eastern Cooperative Oncology Group (ECOG) scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Measured: Up to 5 years
Pharmacokinetics (PK) of ASP1951 in serum: AUClast
Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: AUCinf
Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: AUCinf%extrap
Initial monotherapy escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: AUCtau
Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing to the start of next dosing interval (AUCtau) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: Cmax
Initial monotherapy escalation treatment only. Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: Ctrough
Initial monotherapy escalation and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 48 weeks
Pharmacokinetics (PK) of ASP1951 in serum: tmax
Initial monotherapy escalation treatment only. Time of the maximum concentration (tmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: t 1/2
Initial monotherapy escalation treatment only. Terminal elimination half-life (t1/2) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: tlast
Initial monotherapy escalation treatment only. Time of last measurable concentration (tlast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: CL
Initial monotherapy escalation treatment only. Total clearance after intravenous dosing (CL) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: Vz
Initial monotherapy escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in serum: Vss
Initial monotherapy escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUClast
Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCinf
Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCinf%extrap
Initial combination escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCtau
Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing to the start of next dosing interval (AUCtau) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Cmax
Initial combination escalation treatment only. Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Ctrough
Initial combination escalation and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 48 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: tmax
Initial combination escalation treatment only. Time of the maximum concentration (tmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: t 1/2
Initial combination escalation treatment only. Terminal elimination half-life (t1/2) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: tlast
Initial combination escalation treatment only. Time of last measurable concentration (tlast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: CL
Initial combination escalation treatment only. Total clearance after intravenous dosing (CL) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Vz
Initial combination escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Vss
Initial combination escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be recorded from the pharmacokinetic (PK) serum samples collected.
Measured: Up to 10 weeks
Recommended Phase 2 Dose (RP2D) of ASP1951
RP2D of ASP1951 as a single agent is determined using available data on safety, pharmacokinetics, pharmacodynamics and efficacy of ASP1951.
Measured: Up to 5 years
RP2D of ASP1951 in combination with pembrolizumab
RP2D of ASP1951 in combination with pembrolizumab is determined using available data on safety, pharmacokinetics, pharmacodynamics and efficacy of ASP1951.
Measured: Up to 5 years
Maximum Tolerated Dose (MTD) of ASP1951
MTD is defined as the dose level at which the posterior mean of DLT rate estimated using Bayesian CRM is closest but does not exceed the target DLT rate of 33%, based on the profile of DLTs collected.
Measured: Up to 5 years
MTD of ASP1951 in combination with pembrolizumab
MTD is defined as the dose level at which the posterior mean of DLT rate estimated using Bayesian CRM is closest but does not exceed the target DLT rate of 33%, based on the profile of DLTs collected.
Measured: Up to 5 years
Secondary outcomes (4)
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and modified RECIST 1.1 for immune-based therapeutics (iRECIST)
Initial and retreatment. ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed complete response (CR) or partial response (PR).
Measured: Up to 5 years
Duration of Response (DOR) per RECIST V1.1 and iRECIST
Initial and retreatment. DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
Measured: Up to 5 years
Persistence of response after discontinuation per RECIST V1.1 and iRECIST
Initial and retreatment. Persistence of response is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring.
Measured: Up to 5 years
Disease Control Rate (DCR) per RECIST V1.1 and iRECIST
Initial and retreatment. DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or stable disease (SD).
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2019
- Study start14 Jan 2019
- Primary completion6 Jul 2023
- Study completion6 Jul 2023
Why it stopped: Study was terminated for lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Astellas Pharma Global Development, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Global Development, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Astellas Pharma Global Development, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03799003
- Sponsor's protocol ID
- 1951-CL-0101
- Other IDs
- 2019-002287-27, KEYNOTE-B02, MK-3475-B02, 2019
- Status last verified
- Oct 2024
- First submitted
- 2 Jan 2019
- Last updated
- 1 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study of ASP1951, a GITR Agonistic Antibody, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03799003
- Acronym / sponsor ID
- 1951-CL-0101
- Conditions
- Advanced Solid Tumors
- Keywords
- ASP1951, cervical cancer, Oncology, squamous cell carcinoma of the head and neck (SCCHN), metastatic castration-resistant prostate cancer (mCRPC), melanoma, Tumors, pembrolizumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated for lack of efficacy.
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Astellas Pharma Global Development, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 14 Jan 2019 (actual)
- Primary completion
- 6 Jul 2023 (actual)
- Study completion
- 6 Jul 2023 (actual)
- First posted
- 10 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the tolerability and safety profile of ASP1951 when administered as a single agent and in combination with pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1951 when administered as a single agent and in combination with pembrolizumab; and determine the recommended phase 2 dose (RP2D) of ASP1951 and/or maximum tolerated dose (MTD) when administered as a single agent and in combination with pembrolizumab. This study will also evaluate the anti-tumor effect of ASP1951 when administered as a single agent and in combination with pembrolizumab.
Detailed description
This is a dose-escalation and expansion study of ASP1951. The study consists of 3 periods for monotherapy and combination therapy: screening, treatment and follow up, followed by an optional Re-treatment period for participants that qualify.
The monotherapy escalation cohorts will evaluate escalating dose levels of ASP1951 in participants with locally advanced (unresectable) or metastatic solid tumor malignancies including but not limited to squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer, metastatic castration-resistant prostate cancer (mCRPC) and cervical cancer.
The combination escalation cohorts will evaluate escalating dose levels of ASP1951 in combination with a fixed dose of pembrolizumab.
For dose expansion, the tumor-specific cohorts will include participants with squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC) (all PD-L1 status), NSCLC PDL1 high, and cervical cancer, as well as participants with any tumor types that respond to study drug treatment during dose escalation.
Participants may reinitiate study drug treatment in the optional Re-treatment period after confirmation that the participant meets all the re-treatment eligibility criteria.
After discontinuation of study drug, all participants will complete an end-of-treatment visit, along with 30-day and 90 day safety follow-up visits from the last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| ASP1951 0.07 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 0.07 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 0.7 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 0.7 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 5 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 5 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 20 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 20 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 70 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 70 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 200 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 200 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 700 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 700 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 1400 mg Monotherapy | Experimental | Drug: ASP1951Participants have received ASP1951 1400 mg intravenously on day 1 of every 3-week cycle. |
| ASP1951 20 mg + pembrolizumab 200 mg Combination Therapy | Experimental | Drug: ASP1951, Drug: pembrolizumabParticipants have received ASP1951 20 mg intravenously on day 1 of every 3-week cycle in combination with pembrolizumab 200 mg administered on day 1 of every 3-week cycle, at least 30 minutes after the end of infusion of ASP1951. |
| ASP1951 700 mg + pembrolizumab 200 mg Combination Therapy | Experimental | Drug: ASP1951, Drug: pembrolizumabParticipants have received ASP1951 700 mg intravenously on day 1 of every 3-week cycle in combination with pembrolizumab 200 mg administered on day 1 of every 3-week cycle, at least 30 minutes after the end of infusion of ASP1951. |
| ASP1951 1400 mg + pembrolizumab 200 mg Combination Therapy | Experimental | Drug: ASP1951, Drug: pembrolizumabParticipants have received ASP1951 1400 mg intravenously on day 1 of every 3-week cycle in combination with pembrolizumab 200 mg administered on day 1 of every 3-week cycle, at least 30 minutes after the end of infusion of ASP1951. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (38 listed)
- Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy as well as the following:
- [Taiwan only]: Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy and has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit in the opinion of the treating investigator for his/her specific tumor type. Note: Subjects in the combination expansion cohort with tumor types that pembrolizumab is not approved for can only enroll if their standard treatment is ineffective, unsuitable per investigator's judgment or if the subject is unwilling to receive the standard therapy.
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5-half-lives, whichever is shorter, prior to initiation of study drug administration. A subject with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor therapy until 4 days prior to the start of study drug administration.
- Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 2 weeks prior to study drug administration. Subjects must have recovered from all radiation related toxicities, not require corticosteroids and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks of radiotherapy) to noncentral nervous system [CNS] disease.
Key exclusion criteria (25 listed)
- Subject weighs < 45 kg.
- Subject has received investigational therapy (other than an investigational EGFR TKI in a subject with EGFR activating mutations or ALK inhibitor in a subject with an ALK mutation) within 21 days or 5-half-lives, whichever is shorter, prior to start of study drug.
- Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study drug administration. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone) are allowed.
- Subject has symptomatic CNS metastases or subject has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Subjects with previously treated CNS metastases are eligible, if they are clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone, > 2 mg per day of dexamethasone, or > 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
- Subject has leptomeningeal disease as a manifestation of the current malignancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASP1951Intravenously (IV) | Drug | ASP1951 0.07 mg Monotherapy, ASP1951 0.7 mg Monotherapy, ASP1951 1400 mg + pembrolizumab 200 mg Combination Therapy, ASP1951 1400 mg Monotherapy, ASP1951 20 mg + pembrolizumab 200 mg Combination Therapy, ASP1951 20 mg Monotherapy, ASP1951 200 mg Monotherapy, ASP1951 5 mg Monotherapy, ASP1951 70 mg Monotherapy, ASP1951 700 mg + pembrolizumab 200 mg Combination Therapy, ASP1951 700 mg Monotherapy |
| pembrolizumabAlso: KEYTRUDA®Intravenously (IV) | Drug | ASP1951 1400 mg + pembrolizumab 200 mg Combination Therapy, ASP1951 20 mg + pembrolizumab 200 mg Combination Therapy, ASP1951 700 mg + pembrolizumab 200 mg Combination Therapy |
Primary outcome
Safety and tolerability assessed by Dose Limiting Toxicity (DLT)
Time frame: Up to 5 years
A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 4.03) that the investigator (or sponsor) cannot clearly attribute to a cause other than study drug.
Safety and tolerability assessed by adverse events (AEs)
Time frame: Up to 5 years
Initial and retreatment. An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. AEs will be coded using the medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE 4.03.
Safety and tolerability assessed by immune-related AEs (irAEs)
Time frame: Up to 5 years
Initial and retreatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies (hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency and Type 1 diabetes mellitus). In the event a participant is diagnosed with an irAE, then it should be reported as an AE.
Safety and tolerability assessed by infusion-related reactions (IRRs)
Time frame: Up to 5 years
Initial and retreatment. IRRs are considered AEs of special interest. In the event a participant is diagnosed with an IRR, then it should be reported as an AE.
Safety and tolerability assessed by serious adverse events (SAEs)
Time frame: Up to 5 years
Initial and retreatment. An AE is considered "serious" if it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE). Hospitalization for treatment/observation/examination caused by AE is to be considered as serious; and other medically important events.
Number of participants with laboratory value abnormalities and/or adverse events related to treatment
Time frame: Up to 5 years
Initial and retreatment. Number of participants with potentially clinically significant laboratory values.
Safety and tolerability assessed by 12- lead electrocardiogram (ECG)
Time frame: Up to 5 years
Initial and retreatment. ECGs should be obtained after the participant has rested in supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.
Number of participants with vital signs abnormalities and/or adverse events related to treatment
Time frame: Up to 5 years
Initial and retreatment. Number of participants with potentially clinically significant vital sign values.
Number of participants with Physical Exam abnormalities and/or adverse events related to treatment
Time frame: Up to 5 years
Initial and retreatment. Number of participants with potentially clinically significant physical exam values.
Safety and tolerability assessed by ECOG performance status
Time frame: Up to 5 years
Initial and retreatment. The Eastern Cooperative Oncology Group (ECOG) scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Pharmacokinetics (PK) of ASP1951 in serum: AUClast
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: AUCinf
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: AUCinf%extrap
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: AUCtau
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing to the start of next dosing interval (AUCtau) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: Cmax
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: Ctrough
Time frame: Up to 48 weeks
Initial monotherapy escalation and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: tmax
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Time of the maximum concentration (tmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: t 1/2
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Terminal elimination half-life (t1/2) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: tlast
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Time of last measurable concentration (tlast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: CL
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Total clearance after intravenous dosing (CL) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: Vz
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in serum: Vss
Time frame: Up to 10 weeks
Initial monotherapy escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUClast
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCinf
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCinf%extrap
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCtau
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing to the start of next dosing interval (AUCtau) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Cmax
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Ctrough
Time frame: Up to 48 weeks
Initial combination escalation and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: tmax
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Time of the maximum concentration (tmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: t 1/2
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Terminal elimination half-life (t1/2) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: tlast
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Time of last measurable concentration (tlast) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: CL
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Total clearance after intravenous dosing (CL) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Vz
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be recorded from the pharmacokinetic (PK) serum samples collected.
Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Vss
Time frame: Up to 10 weeks
Initial combination escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be recorded from the pharmacokinetic (PK) serum samples collected.
Recommended Phase 2 Dose (RP2D) of ASP1951
Time frame: Up to 5 years
RP2D of ASP1951 as a single agent is determined using available data on safety, pharmacokinetics, pharmacodynamics and efficacy of ASP1951.
RP2D of ASP1951 in combination with pembrolizumab
Time frame: Up to 5 years
RP2D of ASP1951 in combination with pembrolizumab is determined using available data on safety, pharmacokinetics, pharmacodynamics and efficacy of ASP1951.
Maximum Tolerated Dose (MTD) of ASP1951
Time frame: Up to 5 years
MTD is defined as the dose level at which the posterior mean of DLT rate estimated using Bayesian CRM is closest but does not exceed the target DLT rate of 33%, based on the profile of DLTs collected.
MTD of ASP1951 in combination with pembrolizumab
Time frame: Up to 5 years
MTD is defined as the dose level at which the posterior mean of DLT rate estimated using Bayesian CRM is closest but does not exceed the target DLT rate of 33%, based on the profile of DLTs collected.
4 secondary outcomes
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and modified RECIST 1.1 for immune-based therapeutics (iRECIST)
Time frame: Up to 5 years
Duration of Response (DOR) per RECIST V1.1 and iRECIST
Time frame: Up to 5 years
Persistence of response after discontinuation per RECIST V1.1 and iRECIST
Time frame: Up to 5 years
Disease Control Rate (DCR) per RECIST V1.1 and iRECIST
Time frame: Up to 5 years
Results and safety
The study was stopped early (reason given: Study was terminated for lack of efficacy.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2024.
- Link to results and other applicable study documents on the Astellas Clinical Trials websiteLink provided by the sponsor.
- Link to plain language summary of the study on the Trial Results Summaries websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Astellas Pharma Global Development, Inc.
32 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ASP1951 and pembrolizumab in people with Advanced Solid Tumors, run by Astellas Pharma Global Development, Inc. at 32 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 38 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, South Korea, Canada, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was terminated for lack of efficacy.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability assessed by Dose Limiting Toxicity (DLT) (time frame: Up to 5 years). The study lists 38 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2024.