A Study of APG-1252 in Patients With SCLC or Other Solid Tumors

NCT03080311 | Completed Phase 1 FDA Drug

• 1 other identifier: APG-1252-US-001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

APG-1252 is a highly potent Bcl-2 family protein inhibitor, a promising drug candidate which shown high binding affinities to Bcl-2, Bcl-xL and Bcl-w. The preclinical studies have shown that APG-1252 alone achieves complete and persistent tumor regression in multiple tumor xenograft models with a twice weekly or weekly dose-schedule, including SCLC, colon, breast and acute lymphocytic leukemia (ALL) cancer xenografts; achieves strong synergy with the chemotherapeutic agents, indicating that APG-1252 may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-1252 is intended for the treatment of patients with SCLC or other solid tumors. This is a multi-center, open-label, dose escalation Phase I study to determine the MTD and DLTs of intravenously administered APG-1252. After dose escalation to 240mg twice weekly, 2 dose cohorts two different dosing schedules including weekly and twice weekly will be assessed to evaluate for safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor efficacy. Treatment with APG-1252 will be administered to 30-60 patients at approximately 2 investigational sites in US.

Conditions

Small Cell Lung Cancer; Solid Tumor

Keywords

Bcl-2/Bcl-xL dual inhibitor

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT) determination

  Number of participants with APG-1252 treatment-related adverse events as assessed by NCI CTCAE v4.03

  28 days

• Maximum tolerated dose (MTD) determination

  If ≥ 2/6 patients develop a DLT at any dose level, then this dose will be declared as the MTD

  18 - 24 months

Secondary Outcomes (6)

• Pharmacokinetic evaluation

  18 - 24 months

• Pharmacokinetic evaluation

  18 - 24 months

• Pharmacodynamic evaluation

  18-24 months

• Pharmacodynamic evaluation

  18-24 months

• Pharmacodynamic evaluation

  18-24 months

Study Arms (1)

APG-1252

EXPERIMENTAL

An accelerated dose escalation scheme will be utilized initially with one patient enrolled per cohort. If at 10 mg or 20 mg dose level, any occurrence in cycle 1 of one ≥ Grade 2 adverse event related or possibly related to APG-1252 (graded as per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.0) is the trigger for converting to a standard 3+3 design at that dose level.

Drug: APG-1252

Interventions

APG-1252 DRUG

Multiple dose cohorts, 30 minute IV infusion, twice weekly for 3 weeks of a cycle with 28 days.

Also known as: APG-1252 for injection

APG-1252

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed small cell lung cancer (SCLC) or other solid tumors
• Male or non-pregnant, non-lactating female patients age ≥18 years
• Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator
• Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2
• Adequate hematologic function as indicated by:
• Platelet count ≥ 100,000/mm˄3
• Hemoglobin ≥ 9.0g/dL Platelet count ≥ 100,000/mm˄3
• Absolute neutrophil count (ANC) ≥1000/µL
• Adequate renal and liver function as indicated by:
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is \>1.5 X ULN, creatinine clearance must be ≥ 50 mL/min
• Total bilirubin ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin\> 1.5 x ULN
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3 x ULN of institution's normal range; for patients with known liver metastases, AST and ALT may be ≤ 5 x ULN
• Coagulation: activated partial thromboplastin time (aPTT) and prothrombin time (PT)\<1.2 x the upper limit of normal
• Brain metastases with clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug
• Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug

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, or has had tumor embolization or tumor lysis syndrome (TLS) within 14 days prior to the first dose of study drug
• Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug
• Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to \< Grade 2
• Known bleeding diathesis/disorder
• Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within 1 year prior to first dose of study drug
• Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug)
• Serious gastrointestinal bleeding within 3 months
• Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet 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 28 days prior to the first dose of 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
• Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry
• Neurologic instability 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 including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C)
• Diagnosis of fever and neutropenia within 1 week prior to study drug administration
• Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (2)

START Midwest

Grand Rapids, Michigan, 49503, United States

Location

The START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

pelcitoclax; Injections

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: February 12, 2017
• First Posted: March 15, 2017
• Study Start: February 12, 2017
• Primary Completion: June 22, 2020
• Study Completion: July 17, 2020
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)