Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas

NCT05415098 | Unknown Phase 1 FDA Drug

• 1 other identifier: APG5918XG101
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Nasopharyngeal Carcinoma; Castrate Resistant Prostate Cancer; Gastric Cancer; Ovarian Clear Cell Carcinoma; Mesothelioma; Sarcoma; Non Hodgkin Lymphoma; B Cell Lymphoma; Epithelioid Sarcoma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicity (DLT)

  DLTs will be assessed via CTCAE version 5.0

  28 days

Study Arms (2)

Cohort 1 in Dose expansion

EXPERIMENTAL

Drug: APG-5918

Cohort 2 in Dose expansion

EXPERIMENTAL

Drug: APG-5918

Interventions

APG-5918 DRUG

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.

Cohort 1 in Dose expansion; Cohort 2 in Dose expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (1)

Highlands Oncology

Springdale, Arkansas, 72762, United States

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma; Stomach Neoplasms; Mesothelioma; Sarcoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenoma; Neoplasms, Mesothelial; Neoplasms, Connective and Soft Tissue; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Central Study Contacts

Wendy Chu

CONTACT

240-278-6373; wendy.chu@ascentage.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 10, 2022
• Study Start: September 30, 2022
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2025
• Last Updated: November 16, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)