- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03387332
APG-1252 in Patients With SCLC or Advanced Solid Tumors
August 24, 2021 updated by: Ascentage Pharma Group Inc.
A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Intravenously Administered APG-1252 in Patients With Small Cell Lung Cancer (SCLC) or Advanced Solid Tumors.
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 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.
Upon completion of the Phase 1 dose escalation study to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and/or recommended phase 2 dose (RP2D), several phase Ib/II studies will be implemented accordingly.
Study Overview
Status
Terminated
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510080
- Guangdong General Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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/mm3
- Hemoglobin ≥ 9.0g/dL
- 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 (see Section 22.3).
- 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: aPTT and 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 & 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;
- 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.
Exclusion Criteria:
- 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.
- Prior treatment with Bcl-2/Bcl-xL inhibitors.
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: APG-1252
The starting dose for this study was 40 mg and 1 patient would be enrolled at this dose level.
The dose escalation will convert to a standard 3+3 design following the occurrence of DLT or two ≥ Grade 2 adverse event or at doses 80 mg.
|
Multiple dose cohorts, 30 minute IV infusion, twice weekly for 3 weeks of a cycle with 28 days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limit toxicity (DLT) determination
Time Frame: 18-24 months
|
Number of participants with APG-1252 treatment-related adverse events as assessed by CTCAE v4.03
|
18-24 months
|
Maximum tolerated dose (MTD) determination
Time Frame: 18-24 months
|
If ≥ 2/6 patients develop a DLT at any dose level, then this dose will be declared as the MTD.
|
18-24 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Preliminary efficacy assessment
Time Frame: 18-24 months
|
Patients will be evaluated for response every 2 cycles (i.e., 8 weeks), according to the new response evaluation criteria in solid tumors: revised RECIST Guideline, Version 1.1
|
18-24 months
|
Pharmacokinetic evaluation
Time Frame: 18-24 months
|
Peak plasma concentration (Cmax) will be assessed on all participants with APG-1252 treatments.
|
18-24 months
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic evaluation
Time Frame: 18-24 months
|
Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-1252 treatments
|
18-24 months
|
Pharmacodynamic evaluation
Time Frame: 18-24 months
|
Apoptosis will be assessed on the patients treated with APG-1252
|
18-24 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Yifan Zhai, M.D., Ph.D., Ascentage (Suzhou) Pharma Group Inc
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
December 1, 2017
Primary Completion (ACTUAL)
November 9, 2020
Study Completion (ACTUAL)
April 15, 2021
Study Registration Dates
First Submitted
December 13, 2017
First Submitted That Met QC Criteria
December 28, 2017
First Posted (ACTUAL)
January 2, 2018
Study Record Updates
Last Update Posted (ACTUAL)
August 27, 2021
Last Update Submitted That Met QC Criteria
August 24, 2021
Last Verified
August 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APG-1252-CH-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Small Cell Lung Cancer and Other Solid Tumors
-
Millennium Pharmaceuticals, Inc.TerminatedAdvanced Non-Small Cell Lung Cancer | Other Solid Tumors
-
Jacobio Pharmaceuticals Co., Ltd.RecruitingHead and Neck Cancer | Esophageal Cancer | Non-small Cell Lung Cancer | Other Metastatic Solid TumorsChina
-
Jacobio Pharmaceuticals Co., Ltd.RecruitingHead and Neck Cancer | Esophageal Cancer | Non-small Cell Lung Cancer | Other Metastatic Solid TumorsUnited States
-
Wuhan Union Hospital, ChinaNot yet recruitingUnresectable Advanced Solid Tumors | Biliary Tract Tumors, Gastric Cancer, Small Cell Lung CancerChina
-
Evopoint Biosciences Inc.Merck Sharp & Dohme LLCRecruitingCarcinoma | Cervical Cancer | Prostate Cancer | Squamous Cell Carcinoma of Head and Neck | Non-small Cell Lung Cancer | Small-cell Lung Cancer | Urothelial Carcinoma | Other Solid TumorsChina
-
Ascendis Pharma Oncology Division A/SRecruitingAdvanced Solid Tumor | Metastatic Solid Tumor | Platinum-resistant Ovarian Cancer | Locally Advanced Solid Tumor | Post Anti-PD-1 Melanoma | 2L+ Cervical Cancer | Neoadjuvant Melanoma | Neoadjuvant Non-Small Cell Lung Cancer | Post Anti-PD-(L)1 Non-Small Cell Lung Cancer | Post Anti-PD-(L)1 Small Cell...United States, Australia, Korea, Republic of
-
Revolution Medicines, Inc.RecruitingNon-Small Cell Lung Cancer, NSCLC | KRAS, NRAS, HRAS-mutated NSCLC | KRAS G12C-mutated Solid Tumors, Lung Cancer | Lung Cancer Stage IV, Advanced Solid Tumor, CancerUnited States
-
Bristol-Myers SquibbActive, not recruitingAdvanced Solid Tumors | Non-small Cell Lung CancerUnited States, Italy, Australia, Poland, Spain
-
University of California, DavisNovartis PharmaceuticalsCompletedSolid Tumors | Non-Small Cell Lung Cancer (NSCLC)United States
-
Dana-Farber Cancer InstituteCompletedSolid Tumors | KRAS Mutant Non-Small Cell Lung CancerUnited States
Clinical Trials on APG-1252
-
Ascentage Pharma Group Inc.CompletedSmall Cell Lung Cancer | Solid TumorUnited States
-
Ascentage Pharma Group Inc.RecruitingNeuroendocrine TumorsChina
-
Ascentage Pharma Group Inc.Recruiting
-
Ascentage Pharma Group Inc.WithdrawnMyelofibrosisUnited States
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingEGFR Positive Non-small Cell Lung CancerChina
-
Ascentage Pharma Group Inc.TerminatedSmall Cell Lung CancerUnited States, Australia
-
Affinium Pharmaceuticals, LtdCompletedCellulitis | Wound Infection | Skin and Subcutaneous Tissue Bacterial Infections | Cutaneous Abscess | Burn InfectionUnited States, Canada
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingSolid Tumor | NeuroblastomaChina
-
Ascentage Pharma Group Inc.Suzhou Yasheng Pharmaceutical Co., Ltd.RecruitingEsophageal Cancer | Ovarian Cancer | Non Small Cell Lung Cancer | Malignant Pleural Mesothelioma | Advanced Solid CancerChina
-
Ascentage Pharma Group Inc.RecruitingT-Prolymphocytic LeukemiaUnited States