Study of APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer

NCT04210037 | Terminated Phase 1 FDA Drug

• 1 other identifier: APG1252SU101
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 8

Brief Summary

This is a multi-center, open-label, phase Ib/II study of combination therapy with APG-1252 plus paclitaxel in patients with relapsed/refractory small-cell lung cancer(SCLC). The phase Ib portion will be done using time-to-event continual reassessment method (TITE-CRM) methodology to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of APG-1252 with a fixed dose of paclitaxel. The phase II portion will utilize a Simon two-stage design to determine the efficacy of the combination therapy with response rate as the primary endpoint.

Conditions

Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Primary Toxicity Endpoint: dose-limiting toxicity (DLT)

  DLT will be will be assessed via CTCAE version 5.0

  21 days

• Preliminary efficacy assessment

  Partial or complete response according to RECIST v1.1 criteria measured at anytime with 12 months of start of therapy

  12 months

Study Arms (3)

APG-1252 160 mg

EXPERIMENTAL

intravenous infusion over 30 minutes on days 1, 8 and 15

Drug: APG-1252; Drug: Paclitaxel

APG-1252 240 mg

EXPERIMENTAL

intravenous infusion over 30 minutes on days 1, 8 and 15

Drug: APG-1252; Drug: Paclitaxel

APG-1252 80 mg

EXPERIMENTAL

intravenous infusion over 30 minutes on days 1, 8 and 15

Drug: APG-1252; Drug: Paclitaxel

Interventions

APG-1252 DRUG

APG-1252 (Ascentage Pharma) is a highly potent Bcl-2 family protein inhibitor with high binding affinity for Bcl-2, Bcl-xL and Bcl-w. APG-1252 possesses strong antitumor activity as a single-agent against tumor cells addicted to Bcl-2/Bcl-xL, and exhibits a much broader antitumor activity when combined with chemotherapeutic agents.

APG-1252 160 mg; APG-1252 240 mg; APG-1252 80 mg

Paclitaxel DRUG

80 mg/m˄2 on days 1 and 8 of a 21-day cycle

Also known as: Abraxane

APG-1252 160 mg; APG-1252 240 mg; APG-1252 80 mg

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 SCLC
• Progression of disease on or after initial treatment with platinum-based therapy with or without thoracic radiotherapy; patients may have also received prior immunotherapy or other chemotherapy agents, except for paclitaxel; there is no limit on the number of prior treatment regimens allowed
• Male or non-pregnant, non-lactating female patients
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Adequate hematologic function as indicated by:
• Platelet count ≥ 100,000/mm˄3 Note: Use of transfusions or thrombopoietic agents to achieve baseline platelet count criterion is prohibited.
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1000/µL Note: Use of growth-factors to maintain ANC criterion prior to enrollment is not permitted.
• Adequate renal and liver function as indicated by:
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN); if serum creatinine is \> 1.5 × ULN, creatinine clearance must be ≥ 50 mL/min
• Total bilirubin ≤ 1.5 × ULN; If patient has Gilbert's syndrome, may have bilirubin \> 1.5 × ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; for patients with known liver metastases, AST and ALT may be ≤ 5 × ULN
• Coagulation: activated partial thromboplastin time (aPTT) and prothrombin time (PT) ≤ 1.2 × ULN
• Patients with previously treated, clinically controlled brain metastases are allowed. Clinically controlled is defined as surgical excision and/or radiation therapy followed by at least 14 days of stable neurologic function and no evidence of central nervous system (CNS) disease progression as determined by CT or MRI within 14 days prior to study enrollment. Continued use of corticosteroids is permissible.
• Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential and their partners throughout the treatment period and for at least three months following the last dose of study drug (postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).

You may not qualify if:

• Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy) or any investigational therapy within 14 days prior to the first dose of treatment, with the exception of hormones for hypothyroidism, estrogen replacement therapy (ERT), anti-estrogen analogs, or agonists required to suppress serum testosterone levels
• Continuance of toxicities due to prior treatment that do not recover to \< grade 2, except for clinically insignificant toxicities such as lymphopenia or alopecia
• Known bleeding diathesis/disorder
• Recent history of non-chemotherapy induced thrombocytopenia associated a major bleeding episode within 1 year prior to study entry
• 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 of study entry
• Failure to recover adequately from prior surgical procedures, as judged by the investigator. 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 are excluded. (Minor surgery is invasive operative procedure involving resecting skin or mucus membranes and connective tissue. Major surgery is an invasive operative procedure involving more extensive resection, such as body cavity opening or organ resection.)
• Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry
• Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C); testing for hepatitis B and C is not required for study enrollment
• Uncontrolled concurrent illness that would limit compliance with the study requirements, including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness
• Prior treatment with a Bcl-2/Bcl-xL inhibitor
• Prior treatment with paclitaxel

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (8)

BRCR Medical Center

Plantation, Florida, 33322, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Westmead Hospital

Westmead, New South Wales, 2148, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

pelcitoclax; Paclitaxel; Albumin-Bound Paclitaxel

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Study Design

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

Model Details: APG-1252 at the selected dose-level on days 1, 8 and 15 plus a fixed-dose of paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. There will be three dose-levels of APG-1252 (-1, 80 mg; 1, 160 mg; 2, 240 mg).

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 24, 2019
• Study Start: August 20, 2020
• Primary Completion: August 30, 2021
• Study Completion: May 15, 2022
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); US (6)