Nasopharyngeal CarcinomaPhase 1NCT05415098
Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas
A Phase 1 study testing APG-5918 in people with Nasopharyngeal Carcinoma and Castrate Resistant Prostate Cancer, run by Ascentage Pharma Group Inc. at 1 site in United States.
Trial summary
This is a multicenter, open-label, Phase 1 study that will be conducted in two parts. Part 1 is the dose escalation of APG-5918. Part 2 is the dose expansion of APG-5918. APG-5918 will be administered orally. Patients will be treated in 28-day cycles. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nasopharyngeal Carcinoma, Castrate Resistant Prostate Cancer, Gastric Cancer
- What is being tested?
- APG-5918
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Sep 2022to 30 Sep 2025
- 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
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 in dose escalation or 0 to 2 in dose expansion
- Has a life expectancy of >3 months
- Has a malignancy: with histologically or cytologically confirmed locally advanced or metastatic solid tumors or relapsed or refractory Non-Hodgkin's Lymphoma (NHL) who have disease progression after treatment with available therapies that are known to confer clinical benefit.
- has measurable disease based on RECIST 1.1 for advanced solid tumors including but not limited to nasopharyngeal carcinoma, castration-resistant prostate cancer, gastric cancer, ovarian clear cell carcinoma, mesothelioma, and sarcoma
- has measurable disease based on Non-Hodgkin's Lymphoma Cheson response criteria for NHL
- For subjects with B cell lymphoma: has documented EZH2 mutation status or be willing to perform EZH2 mutation status testing
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- For subjects with sarcoma: patients with epithelioid sarcoma or sarcoma with confirmed evidence of aberrant SMARCB1 status is preferred
- For subjects with prostate cancer: patients must have evidence of castration resistance (as evidenced by confirmed elevated prostate-specific antigen (PSA) (per Prostate Cancer Working Group [PCWG3] criteria) and serum testosterone of castrate levels (i.e. ≤ 50 ng/dL))
- Adequate hematologic function defined as:
- ANC ≥1.0 x 10˄9/L independent of growth factor support within 7 days of the first dose with study drug
- Hemoglobin ≥9 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug
- Platelet count ≥ 75 x 10˄9/L without transfusion support within 7 days of the first dose of study drug
- Adequate hepatic and renal function defined as:
- AST and ALT ≤ 3 x upper limit of normal (ULN) (≤ 5 x ULN if liver metastases)
- Calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula
- Total Bilirubin ≤1.5 x ULN (Except if considered secondary to Gilbert's syndrome and primarily indirect bilirubinemia)
- PT and aPTT ≤2 x ULN
- Troponin ≤ 2 x ULN
- QTcF interval ≤470ms for all genders (mean (triplicate) n =3), measured between 2-5 minutes apart
- Stable brain metastases with clinically controlled neurologic symptoms
- Willingness to use contraception by either true abstinence or the use of a method that is deemed effective by the investigator by both males and female patients of childbearing potential and their partners throughout the treatment period and for at least three months following the last dose of study drug. Note: Female participants of non-child-bearing potential are defined as:
- surgically sterile,
- postmenopausal for 12 months, or
- receiving a stable dose of oral, implanted, transdermal or injectable contraceptive for at least 3 months with the last dose of injectable contraceptive within 2 months (Nonsurgical menopause history must be confirmed by follicle-stimulating hormone and luteinizing hormone levels as defined by established laboratory ranges)
- Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures)
- Willingness and ability to comply with study procedures and follow-up examination
Who cannot join
- Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti-estrogen analogs, agonists required to suppress serum testosterone levels); or any investigational therapy within 14 days or 5 times of half-life of the molecule prior to the first dose of study drug
- Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of the study drug
- Continuance of toxicities due to prior radiotherapy, targeted therapy, immunotherapy or chemotherapeutic agents that do not recover to < Grade 2, except alopecia or leukodermia
- Has gastrointestinal conditions that could affect the absorption of APG-5918 in the opinion of the Investigator
- Use of therapeutic doses of anti-coagulants is excluded, along with antiplatelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted
- Received a biologic (G-CSF, GM-CSF, or erythropoietin) within 7 days prior to the first dose of the study drug
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- Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry.
- Severe cardiac conditions defined as:
- New York Heart Association (NYHA) class III or IV cardiac disease, including preexisting uncontrolled clinically significant arrhythmia, congestive heart failure, or cardiomyopathy
- Unstable angina, myocardial infarction, or a coronary revascularization procedure within ≤ 3 months prior to initiation of study treatment
- Echocardiography showing left ventricular ejection fraction (LVEF) < 50%
- poorly controlled hypertension, or history of poor compliance with antihypertensive drug regimens
- Symptomatic brain metastases per clinical evaluation due to tumor involvement of the central nervous system (CNS). Patients with CNS tumors that have been treated are asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for ≤ 28 days may be enrolled.
- Active symptomatic fungal, bacterial, and/or viral infection. Patients with well controlled human immunodeficiency virus (HIV), hepatitis B or C can be enrolled.
- Prior treatment with embryonic ectoderm development (EED) inhibitors
- Concurrent treatment with QT interval-prolonging drugs
- Medical history of Torsades de Pointes
- Patients with known or suspected allergy or hypersensitivity to drugs/compounds similar in composition to APG-5918 or other EED inhibitors
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study
- Other malignant diseases than the ones being treated in this study with the exception of: cured malignancy without recurrence within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of any type
- Non-Hodgkin lymphoma patients who have received prior allogeneic stem cell transplant
- Severe and/or uncontrolled medical conditions that in the investigator's opinion could affect the safety of individual or impair the assessment of study result
- Long-term steroid therapy, except for the following: 10 mg prednisone (or equivalent) daily or lower doses of steroids for control of nausea, vomiting, active autoimmune disease and seasonal allergies or prevention of adrenocortical insufficiency Note: topical steroids or inhaled steroids are allowed
- Pregnant (confirmed by human chorionic gonadotropin (HCG) testing) or lactating women
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Highlands Oncology
Springdale, Arkansas, 72762
Thad Beck, MD
About this study
Official title: A Phase I Study of Safety, Pharmacokinetic and Efficacy of Orally Administered APG-5918 in Patients With Advanced Solid Tumors or Hematologic Malignancies
This is a multicenter, open-label, Phase 1 study that will be conducted in two parts. Part 1 is the dose escalation of APG-5918. Part 2 is the dose expansion of APG-5918.
APG-5918 will be administered orally. Patients will be treated in 28-day cycles.
Read the detailed description
The dose escalation part is to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) when APG-5918 is given orally once daily in subjects with histologically- and/or cytologically-confirmed advanced solid tumors or non-Hodgkin's lymphoma (NHL) that have progressed or are intolerant after treatment with approved therapies or for which there are no standard therapies available. The starting dose of APG-5918 is 50 mg; the doses can be modified depending on toxicity and pharmacokinetic (PK) results based on discussions with the Investigators and Sponsor. If no dose-limiting toxicities (DLTs) or less than two drug related Grade 2 toxicities are observed by the end of Cycle 1, the dose of APG-5918 will be increased in subsequent cohorts.
The dose expansion part will be initiated once the MTD or RP2D is established. Approximately 9-12 subjects will be enrolled into two cohorts treating with the appropriate two dose levels at (MTD-1 and MTD) or below MTD (MTD-2 and MTD-1), depending on the comprehensive analysis of the PK, pharmacodynamic (PD), safety and efficacy data of APG-5918. Patients will be randomized 1:1 to each dose cohort.
- Conditions
- Nasopharyngeal Carcinoma, Castrate Resistant Prostate Cancer, Gastric Cancer, Ovarian Clear Cell Carcinoma, Mesothelioma, Sarcoma
- Being tested
- APG-5918
- Medical subject headings
- Nasopharyngeal Carcinoma, Stomach Neoplasms, Mesothelioma, Sarcoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-5918Drug
The investigational drug product is formulated as oral tablets of 50 mg or 200 mg that contain APG-5918 as the active ingredient. APG-5918 will be orally administered once every day on 28-day cycles.
The dosage of APG-5918 depends on the dose level to which the patient is assigned. Each dose of APG-5918 will be taken orally in fasted condition in the study.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 in Dose expansion | Experimental | Not described Receives: Drug: APG-5918 |
| Cohort 2 in Dose expansion | Experimental | Not described Receives: Drug: APG-5918 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting Toxicity (DLT)
DLTs will be assessed via CTCAE version 5.0
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start30 Sep 2022
- Primary completion30 Sep 2024 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yifan Zhai, MD, PhD, Study chair, Ascentage Pharma Group Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05415098
- Sponsor's protocol ID
- APG5918XG101
- Status last verified
- Nov 2022
- First submitted
- 8 Jun 2022
- Last updated
- 16 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Safety, Pharmacokinetic and Efficacy of Orally Administered APG-5918 in Patients With Advanced Solid Tumors or Hematologic Malignancies
- ClinicalTrials.gov ID
- NCT05415098
- Acronym / sponsor ID
- APG5918XG101
- Conditions
- Nasopharyngeal Carcinoma, Castrate Resistant Prostate Cancer, Gastric Cancer, Ovarian Clear Cell Carcinoma, Mesothelioma, Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Sep 2022 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 10 Jun 2022 (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.
This is a multicenter, open-label, Phase 1 study that will be conducted in two parts. Part 1 is the dose escalation of APG-5918. Part 2 is the dose expansion of APG-5918.
APG-5918 will be administered orally. Patients will be treated in 28-day cycles.
Detailed description
The dose escalation part is to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) when APG-5918 is given orally once daily in subjects with histologically- and/or cytologically-confirmed advanced solid tumors or non-Hodgkin's lymphoma (NHL) that have progressed or are intolerant after treatment with approved therapies or for which there are no standard therapies available. The starting dose of APG-5918 is 50 mg; the doses can be modified depending on toxicity and pharmacokinetic (PK) results based on discussions with the Investigators and Sponsor. If no dose-limiting toxicities (DLTs) or less than two drug related Grade 2 toxicities are observed by the end of Cycle 1, the dose of APG-5918 will be increased in subsequent cohorts.
The dose expansion part will be initiated once the MTD or RP2D is established. Approximately 9-12 subjects will be enrolled into two cohorts treating with the appropriate two dose levels at (MTD-1 and MTD) or below MTD (MTD-2 and MTD-1), depending on the comprehensive analysis of the PK, pharmacodynamic (PD), safety and efficacy data of APG-5918. Patients will be randomized 1:1 to each dose cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 in Dose expansion | Experimental | Drug: APG-5918 |
| Cohort 2 in Dose expansion | Experimental | Drug: APG-5918 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 in dose escalation or 0 to 2 in dose expansion
- Has a life expectancy of >3 months
- Has a malignancy: with histologically or cytologically confirmed locally advanced or metastatic solid tumors or relapsed or refractory Non-Hodgkin's Lymphoma (NHL) who have disease progression after treatment with available therapies that are known to confer clinical benefit.
- For subjects with B cell lymphoma: has documented EZH2 mutation status or be willing to perform EZH2 mutation status testing
- For subjects with sarcoma: patients with epithelioid sarcoma or sarcoma with confirmed evidence of aberrant SMARCB1 status is preferred
Key exclusion criteria (24 listed)
- Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti-estrogen analogs, agonists required to suppress serum testosterone levels); or any investigational therapy within 14 days or 5 times of half-life of the molecule prior to the first dose of study drug
- Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of the study drug
- Continuance of toxicities due to prior radiotherapy, targeted therapy, immunotherapy or chemotherapeutic agents that do not recover to < Grade 2, except alopecia or leukodermia
- Has gastrointestinal conditions that could affect the absorption of APG-5918 in the opinion of the Investigator
- Use of therapeutic doses of anti-coagulants is excluded, along with antiplatelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted
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 |
|---|---|---|
| APG-5918The investigational drug product is formulated as oral tablets of 50 mg or 200 mg that contain APG-5918 as the active ingredient. APG-5918 will be orally administered once every day on 28-day cycles. The dosage of APG-5918 depends on the dose level to which the patient is assigned. Each dose of APG-5918 will be taken orally in fasted condition in the study. | Drug | Cohort 1 in Dose expansion, Cohort 2 in Dose expansion |
Primary outcome
Dose-limiting Toxicity (DLT)
Time frame: 28 days
DLTs will be assessed via CTCAE version 5.0
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 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.
Yifan Zhai, MD, PhD study chair
Ascentage Pharma Group Inc.
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 APG-5918 in people with Nasopharyngeal Carcinoma and Castrate Resistant Prostate Cancer, run by Ascentage Pharma Group Inc. at 1 site in United States.
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 26 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 16 Nov 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 United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Wendy Chu (240-278-6373, wendy.chu@ascentage.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting Toxicity (DLT) (time frame: 28 days). 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 16 Nov 2022.