A Study of APG-1252 Plus Osimertinib(AZD9291) in EGFR TKI Resistant NSCLC Patients

NCT04001777 | Active Not Recruiting Phase 1

• 1 other identifier: APG1252NC101
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

Brief Summary

There are unmet medical needs in patients who resist to EGFR TKIs, especially to osimertinib; APG-1252 shows synergy with osimertinib in both osimertinib treatment naïve and resistant cell lines. This study is to explore the safety and efficacy of the combination of APG-1252 and osimertinib in 3rd generation TKI resistant patients and 3rd generation TKI treatment naïve patients.

Conditions

EGFR Positive Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD)

  To determine the maximum tolerated dose (MTD) of APG-1252 in subjects with NSCLC

  21 days

• Recommended Phase 2 dose (RP2D)

  Recommended Phase 2 dose (RP2D) of APG-1252 in subjects with NSCLC

  21 days

Secondary Outcomes (1)

• efficacy assessment: Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

  Every 6 weeks up to 2 years

Study Arms (1)

APG-1252 plus Osimertinib (AZD9291)

EXPERIMENTAL

APG-1252 will be explored sequentially using a standard 3+3 escalation scheme at the dose escalation phase; Dose of osimertinib will be fixed at 80mg QD based on approved label.

Drug: APG-1252; Drug: Osimertinib Mesylate Tablets

Interventions

APG-1252 DRUG

Multiple dose cohorts, 30 minute IV infusion, weekly for 3 weeks of a cycle with 21days.

Also known as: APG-1252 for injection

APG-1252 plus Osimertinib (AZD9291)

Osimertinib Mesylate Tablets DRUG

Osimertinib Mesylate Tablets 40mg/80 mg, one time a day until disease progression

Also known as: AZD9291

APG-1252 plus Osimertinib (AZD9291)

Eligibility Criteria

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

You may qualify if:

• Only applicable to the dose-finding stage:
• Patients with NSCLC with disease progression after first-line EGFR TKI and platinum-based chemotherapy.
• Only applicable to dose-expansion stage:
• Cohort 1: Patients with NSCLC with disease progression after third-generation EGFR TKI and platinum-based chemotherapy.
• Cohort 2: Patients with NSCLC with disease progression after first- or second-generation EGFR TKI and platinum-based chemotherapy.
• Cohort 3: Patients with advanced EGFR-mutated NSCLC not previously treated with TKI.
• Applicable to any phase:
• Histologically or cytologically confirmed incurable advanced or metastatic non-small cell lung cancer.
• At least 1 measurable lesion (RECIST 1.1).
• Confirmed EGFR mutation positive before start use prior EGFR TKI(s) .
• Willing to biopsy or to supply achieved tumor sample which biopsy after the most recent treatment.
• Male or female patients age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
• Estimated OS ≥3 months.
• Adequate hematologic and bone marrow functions.

You may not qualify if:

• Received chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy (hormones for hypothyroidism or estrogen replacement therapy (ERT), anti-estrogen analogs, agonists required to suppress serum testosterone levels are permitted); or any investigational therapy; , or has had tumor embolization or tumor lysis syndrome (TLS) within 28 days prior to the first dose of study drug.
• Received TKIs targeted therapy (except third generation EGFR TKIs) within 14 days prior to the first dose of study drug.
• A history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease.
• Any of the following cardiac criteria: screening period resting period QTC \> 470 milliseconds (clinical electrocardiograph report value; if a single time\> 470 milliseconds, take the average of 3 inspections); rhythm of resting electrocardiogram (ECG), any clinically important abnormality of conduction or morphology (e.g., complete left bundle branch block, Grade 3 heart block, Grade 2 heart block); family history of congenital long QT prolongation syndrome or long QT syndrome.
• Evidence of any serious or uncontrolled systemic disease; various chronic active infections such as hepatitis B (HBV-DNA ≥ 104 copy number/ml or 2000 IU/ml), hepatitis C and HIV; uncontrollable Hypertensive patients (requires 2 or more drugs to control blood pressure); unstable angina; angina pectoris within 3 months prior to study; congestive heart failure (NYHA class II or higher); myocardial infarction (NSTEMI or STEMI) history in 6 months before study enrollment; severe arrhythmia requiring medical attention; severe liver, kidney, gastrointestinal or metabolic diseases.
• Patients who are unable to stop taking drugs or herbal medicine that are strong inhibitors or inducers of CYP3A within 1 week before the first study drug administration and during the treatment. However, patients who discontinue use of these compounds at least 1 week prior to receiving this regimen are eligible.
• Hemorrhagic constitution/disease, such as a history of non-chemotherapy-induced thrombocytopenic hemorrhage or a history of ineffective platelet transfusion within 1 year prior to the first dose of study drug; Severe gastrointestinal bleeding occurred within 3 months prior to the first dose of study drug; Active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), etc.
• Use a therapeutic dose of anticoagulant or antiplatelet agent before the first use of APG-1252 or within 7 days of central catheter placement (if platelet count is stable (≧50×109/L), Subjects who previously received aspirin to prevent thrombosis therapy can reuse low-dose aspirin (i.e., up to 100 mg QD) after 3 weeks of study drug treatment; Decisions regarding anticoagulants and antiplatelet therapy will be determined by the investigator and the sponsor; Allow low-dose anticoagulant drugs to maintain central venous catheters open.
• Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the first dose of study drug.
• According to the investigator's judgment, patients who did not fully recover after surgery. Patients who underwent major surgery within 28 days prior to the first study drug and who underwent minor surgery within 7 days prior to the start of the study.
• Other malignancies have been diagnosed within 5 years prior to the first use of the study drug; except effectively treated skin basal cell carcinoma, cutaneous squamous cell carcinoma, and/or effectively resected orthotopic cervical cancer and/or breast cancer.
• Female patients during pregnancy or lactation.
• Previous allergies or intolerance to treatment with osimertinib.
• A diagnosis of febrile neutropenia within one week prior to the first use of the study drug.
• Prior treatment with Bcl-2/Bcl-xL inhibitors.

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead
• Suzhou Yasheng Pharmaceutical Co., Ltd.: collaborator

Study Sites (4)

Sun-Yat Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Henan Provincial people's Hospital

Zhengzhou, Henan, China

Location

First Hospital of Jilin University

Changchun, Jilin, China

Location

Jilin Provincial Cancer Hospital

Changchun, Jilin, China

Location

MeSH Terms

Interventions

pelcitoclax; Injections; osimertinib

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Li Zhang, Professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: June 28, 2019
• Study Start: July 4, 2019
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)