Solid TumorsPhase 1NCT04009460
A Study of ES101 (PD-L1x4-1BB Bispecific Antibody) in Patients With Advanced Solid Tumors
A Phase 1 study testing ES101 in people with Solid Tumors and Neoplasms, run by Elpiscience Biopharma, Ltd. at 1 site in China.
Trial summary
The purpose of this study is to evaluate the safety, tolerance and Dose-Limiting Toxicity (DLT) of recombinant humanized PD-L1/4-1BB bispecific antibody (ES101) in patients with advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors, Neoplasms, Malignant Tumor
- What is being tested?
- ES101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 28 Jun 2019to 22 Apr 2022
- 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
- Males or females aged ≥ 18 years.
- Subject has pathological or cytological diagnosed advanced malignant solid tumor, whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options
- Part A: There is no mandatory requirement for PD-L1 expression status of subject's tumor tissue. Part B:Tumor tissue of subject should be PD-L1 positivity by immunohistochemistry (IHC).
- Subjects in part A shall have at least one evaluable lesion, and subjects enrolled in part B shall have at least one measurable lesion (RECIST v1.1). Tumor lesions located in previously irradiated (or other local treated) areas will be considered measurable, provided that there has been clear imaging-based progression of the lesions since the time of radiation.
- Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
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- Estimated life expectancy, in the judgment of the investigator, of at least 12 weeks.
- Male and female subjects of childbearing potential and their spouses must be willing to use feasible contraceptive methods considered effective by the investigator, from the time of signing informed consent and for the duration of study participation through 3 months, following the last dose of study drug. Postmenopausal women are considered to have no fertility potential only if menostasis lasts for at least 12 months.
- Ability to understand and the willingness to sign a written informed consent form
Who cannot join
- Prior exposure to 4-1BB agonists.
- Receipt of any anticancer investigational product or any approved drug(s) or biological products (except hormone-replacement therapy, testosterone or oral contraceptives) within 4 weeks prior to the first dose of study drug. Previous exposure to oral fluorouracils or small molecular targeted drugs require a minimum washout period of 2 weeks or 5 half-lives prior to the first dose of study drug (whichever is longer). Previous exposure to mitomycin C or nitrosourea requires a minimum washout period of 6 weeks prior to the first dose of study drug.
- Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES101.
- Primary or metastatic brain or meningeal tumors.
- Patients with other malignancies previously or currently shall be excluded in Part B.
- Grade ≥ 3 immune-related adverse events (irAEs) or irAE that lead to discontinuation of prior immunotherapy. Some exceptions as defined per protocol apply.
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- Active autoimmune disease or documented history of autoimmune disease that required systemic steroids or other immunosuppressive medications. Certain exceptions as defined in protocol apply.
- Treatment with systemic immunosuppressive medications within 4 weeks prior to the first dose of study drug. Certain exceptions as defined in protocol apply.
- Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment with steroids or immunosuppressive medications..
- Subjects who received G-CSF, GM-CSF, Thrombopoietic drugs or EPO within 14 days prior to the first dose of the study drug.
- Any evidence of hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection.
- History of hepatitis (non-alcohol steatohepatitis, alcohol or drug-related, autoimmune) or cirrhosis.
- Clinically significant cardiac condition.
- History of pulmonary embolism within 12 weeks prior to the first dose of study drug.
- Major surgery within 4 weeks prior to enrollment on this trial.
- Systemic anti-infectious drug treatments within 4 weeks prior to the first dose of study drug.
- Prior organ allograft transplantations or allogeneic peripheral blood stem cell (PBSC) or bone marrow (BM) transplantation.
- Live viral vaccine therapies within 4 weeks prior to the first dose of study drug.
- Subject has not recovered from all AEs of previous anticancer therapies to baseline or ≤ Grade 1 per CTCAE v5.0 before teh first dose of study drug. Certain exceptions as defined in protocol apply.
- Pregnant or nursing females.
- Any known, documented, or suspected history of substance abuse that would preclude subject from participation, unless clinically justified (i.e., will not interfere with study participation and/or will not compromise trial objectives) per judgment of the Investigator and with approval of the Medical Monitor or Study Director.
- The subject is inappropriate to participate in this study for other reasons in the judgment of the Investigator.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Multicenter, Dose-escalation and Cohort Expansion Phase 1 Clinical Study of ES101 in Patients With Advanced Solid Tumors
The purpose of this study is to evaluate the safety, tolerance and Dose-Limiting Toxicity (DLT) of recombinant humanized PD-L1/4-1BB bispecific antibody (ES101) in patients with advanced solid tumors.
Read the detailed description
ES101 (INBRX-105; PDL1x4-1BB antibody) is a recombinant humanized bispecific IgG1 antibody targeting human PD-L1 and 4-1BB. This is an open-label, multicenter, dose-escalation and cohort expansion phase 1 clinical study to evaluate the safety and pharmacokinetic characteristics and preliminary anti-tumor activity of ES101 in patients with advanced malignant solid tumors whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options.
- Conditions
- Solid Tumors, Neoplasms, Malignant Tumor
- Being tested
- ES101
- Keywords
- ES101, solid tumor, phase 1, PD-L1, 4-1BB, INBRX-105, PD-L1×4-1BB, 41BB, PDL1
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ES101Drug
ES101 is administered via intravenous infusion, once every 14 days, every 28 days as a treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Part A dose escalation | Experimental | ES101 will be escalated in patients with advanced solid tumors. Receives: Drug: ES101 |
| Part B expansion | Experimental | Subjects with solid tumors will be treated with single-agent ES101 at either specified dose levels or RP2D. Receives: Drug: ES101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of of ES101
The MTD and/or RP2D of ES101 will be determined.
Measured: Up to 2-3 years
Frequency of adverse events of ES101
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Measured: Up to 2-3 years
Severity of adverse events of ES101
Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Measured: Up to 2-3 years
Secondary outcomes (6)
Area under the serum concentration time curve (AUC) of ES101
Area under the serum concentration time curve (AUC) of ES101 will be determined.
Measured: Up to 2-3 years
Maximum observed serum concentration (Cmax) of ES101
Maximum observed serum concentration (Cmax) of ES101 will be determined.
Measured: Up to 2-3 years
Trough observed serum concentration (Ctrough) of ES101
Trough observed serum concentration (Cmax) of ES101 will be determined.
Measured: Up to 2-3 years
Time to Cmax (Tmax) of ES101
Time to Cmax (Tmax) of ES101 will be determined.
Measured: Up to 2-3 years
Immunogenicity of ES101
Frequency of anti-drug antibodies (ADA) against ES101 will be determined.
Measured: Up to 2-3 years
Anti-tumor activity of ES101
Tumor response will be determined by the revised Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1).
Measured: Up to 2-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start28 Jun 2019
- Primary completion22 Apr 2022
- Study completion22 Apr 2022
Why it stopped: Sponsor's clinical development strategy adjustment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- 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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Elpiscience Biopharma, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04009460
- Sponsor's protocol ID
- ES101-1001
- Other IDs
- CTR20190888
- Status last verified
- Apr 2022
- First submitted
- 3 Jul 2019
- Last updated
- 29 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Dose-escalation and Cohort Expansion Phase 1 Clinical Study of ES101 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04009460
- Acronym / sponsor ID
- ES101-1001
- Conditions
- Solid Tumors, Neoplasms, Malignant Tumor
- Keywords
- ES101, solid tumor, phase 1, PD-L1, 4-1BB, INBRX-105, PD-L1×4-1BB, 41BB
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor's clinical development strategy adjustment
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Elpiscience Biopharma, Ltd.Industry (pharma, biotech, devices)
- Study start
- 28 Jun 2019 (actual)
- Primary completion
- 22 Apr 2022 (actual)
- Study completion
- 22 Apr 2022 (actual)
- First posted
- 5 Jul 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 purpose of this study is to evaluate the safety, tolerance and Dose-Limiting Toxicity (DLT) of recombinant humanized PD-L1/4-1BB bispecific antibody (ES101) in patients with advanced solid tumors.
Detailed description
ES101 (INBRX-105; PDL1x4-1BB antibody) is a recombinant humanized bispecific IgG1 antibody targeting human PD-L1 and 4-1BB. This is an open-label, multicenter, dose-escalation and cohort expansion phase 1 clinical study to evaluate the safety and pharmacokinetic characteristics and preliminary anti-tumor activity of ES101 in patients with advanced malignant solid tumors whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A dose escalation | Experimental | Drug: ES101ES101 will be escalated in patients with advanced solid tumors. |
| Part B expansion | Experimental | Drug: ES101Subjects with solid tumors will be treated with single-agent ES101 at either specified dose levels or RP2D. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males or females aged ≥ 18 years.
- Subject has pathological or cytological diagnosed advanced malignant solid tumor, whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options
- Part A: There is no mandatory requirement for PD-L1 expression status of subject's tumor tissue. Part B:Tumor tissue of subject should be PD-L1 positivity by immunohistochemistry (IHC).
- Subjects in part A shall have at least one evaluable lesion, and subjects enrolled in part B shall have at least one measurable lesion (RECIST v1.1). Tumor lesions located in previously irradiated (or other local treated) areas will be considered measurable, provided that there has been clear imaging-based progression of the lesions since the time of radiation.
- Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
Key exclusion criteria (22 listed)
- Prior exposure to 4-1BB agonists.
- Receipt of any anticancer investigational product or any approved drug(s) or biological products (except hormone-replacement therapy, testosterone or oral contraceptives) within 4 weeks prior to the first dose of study drug. Previous exposure to oral fluorouracils or small molecular targeted drugs require a minimum washout period of 2 weeks or 5 half-lives prior to the first dose of study drug (whichever is longer). Previous exposure to mitomycin C or nitrosourea requires a minimum washout period of 6 weeks prior to the first dose of study drug.
- Known allergies to CHO-produced antibodies, which in the opinion of the Investigator suggests an increased potential for an adverse hypersensitivity to ES101.
- Primary or metastatic brain or meningeal tumors.
- Patients with other malignancies previously or currently shall be excluded in Part B.
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 |
|---|---|---|
| ES101ES101 is administered via intravenous infusion, once every 14 days, every 28 days as a treatment cycle. | Drug | Part A dose escalation, Part B expansion |
Primary outcome
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of of ES101
Time frame: Up to 2-3 years
The MTD and/or RP2D of ES101 will be determined.
Frequency of adverse events of ES101
Time frame: Up to 2-3 years
Adverse events will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
Severity of adverse events of ES101
Time frame: Up to 2-3 years
Severity of adverse events will be assessed and assigned by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.
6 secondary outcomes
Area under the serum concentration time curve (AUC) of ES101
Time frame: Up to 2-3 years
Maximum observed serum concentration (Cmax) of ES101
Time frame: Up to 2-3 years
Trough observed serum concentration (Ctrough) of ES101
Time frame: Up to 2-3 years
Time to Cmax (Tmax) of ES101
Time frame: Up to 2-3 years
Immunogenicity of ES101
Time frame: Up to 2-3 years
Anti-tumor activity of ES101
Time frame: Up to 2-3 years
Results and safety
The study was stopped early (reason given: Sponsor's clinical development strategy adjustment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2022.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ES101 in people with Solid Tumors and Neoplasms, run by Elpiscience Biopharma, Ltd. at 1 site in China.
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 9 inclusion and 22 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 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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: Sponsor's clinical development strategy adjustment). 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?
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of of ES101 (time frame: Up to 2-3 years). The study lists 3 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 29 Apr 2022.