APG-2575 Monotherapy or in Combination With Lenalidomide/DXMS in Subjects With Relapsed or Refractory Multiple Myeloma

Phase Ib / II Open-Label Stduy of APG-2575 Monotherapy or in Combination With Lenalidomide / Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy, and PK/ Pharmacodynamics of APG2575 monotherapy or in combination with lenalidomide (R) and dexamethasone (d) in patients with relapsed/refractory (R/R) multiple myeloma (MM). The primary objective is to evaluate the safety and tolerability, identify dose-limiting toxicities (DLT), the maximum tolerated dose (MTD) and the recommended dose (RP2D) of APG-2575 monotherapy or in combination with Rd in Chinese R/R MM patients.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: APG-2575; Drug: Rd

Detailed Description

This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy, and PK/ Pharmacodynamics of APG2575 monotherapy or in combination with lenalidomide (R) and dexamethasone (d) in patients with relapsed/refractory (R/R) multiple myeloma (MM). The primary objective is to evaluate the safety and tolerability, identify dose-limiting toxicities (DLT), the maximum tolerated dose (MTD) and the recommended dose (RP2D) of APG-2575 monotherapy or in combination with Rd in Chinese R/R MM patients.

This study consists of two arms of APG-2575 single agent (arm A) and APG-2575 in combination with Rd (arm B). All subjects will receive consecutive treatment in 28-day cycles.

All subjects will continue to receive treatment until disease progression, unacceptable toxicities, or other treatment discontinuation criteria fdefined by the protocol. All subjects will complete survival follow up after treatment discontinuation until end of the study, withdrawal of informed consent, loss of follow-up, or death.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jianping Ning; Phone Number: +86-010-67091790; Email: jianping.ning@ascentage.com
• Study Contact Backup: Name: Bo Huang; Phone Number: +86-020-28068500; Email: bo.huang@ascentage.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100020
      • Not yet recruiting
      • Beijing Chao-yang Hospital of Capital Medical University
      • Contact: Zhongxia Huang, Ph.D
      • Principal Investigator: Zhongxia Huang, Ph.D
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Not yet recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Zhongjun Xia, Ph.D
      • Principal Investigator: Zhongjun Xia, Ph.D
    • Guangzhou, Guangdong, China, 510080
      • Not yet recruiting
      • Guangdong Province People's Hospital
      • Contact: Jianyu Weng, Ph.D
      • Principal Investigator: Jianyu Weng, Ph.D
    • Guangzhou, Guangdong, China, 510080
      • Not yet recruiting
      • The First Affiliated Hospital of Sun Yat-Sen University
      • Contact: Juan Li, Ph.D
      • Principal Investigator: Juan Li, Ph.D
    • Shenzhen, Guangdong, China, 518025
      • Not yet recruiting
      • Shenzhen Second People's Hospital
      • Contact: Xin Du, Ph.D
      • Principal Investigator: Xin Du, Ph.D
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Not yet recruiting
      • Henan Cancer Hospital
      • Principal Investigator: Baijun Fang, Ph.D
  • Hubei
    • Wuhan, Hubei, China, 215316
      • Not yet recruiting
      • Union Hospital Tongji Medical College of Huazhong University of Science ang Technology
      • Contact: Mei Hong, Ph.D
      • Principal Investigator: Mei Hong, Ph.D
    • Wuhan, Hubei, China, 430062
      • Not yet recruiting
      • Zhongnan Hospital of Wuhan University
      • Principal Investigator: Fuling Zhou, Ph.D
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Not yet recruiting
      • People's hospital of Jiangsu Province
      • Contact: Lijuan Chen, Ph.D
      • Principal Investigator: Lijuan Chen, Ph.D
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Zhengzheng Fu, MD.; Phone Number: +86-0512-67781856; Email: fuzhengzheng@suda.edu.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Not yet recruiting
      • The First Affilated Hospital of Zhejiang University School of Medicine
      • Principal Investigator: Zhen Cai, Ph.D
      • Contact: Zhen Cai, Ph.D
    • Hangzhou, Zhejiang, China, 310003
      • Not yet recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Wenbin Qian, Ph.D
      • Principal Investigator: Wenbin Qian, Ph.D

Participation Criteria

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:

1. ≥ 18 years of age;
2. Life expectancy ≥ 6 months;
3. Eastern Cooperative Oncology Group (ECOG) ≤ 2;
4. Corrected QT interval (QTc) based on Frederica or Bazett formula ≤ ≤450ms (male)，or ≤ 470ms (female);
5. Patients with Relapsed/Refractory MM, previously treated with at least 1 prior line of therapy for MM;
6. Symptomatic MM patients with measurable disease (IMWG 2016);
7. Patients with a history of autologous HSCT must have an adequate bone marrow function and have recovered from any transplant-related toxicity, and meet a minimum of 6 months post-autologous transplant (prior to first dose).
8. Adequate hematologic function without growth factor support
9. Adequate hepatic, renal and coagulation function
10. Male and female subjects of childbearing potential who agree to use highly effective methods of birth control during the period of therapy and for 90 days after the last dose of study drug.
11. Ability to understand and voluntarily sign a written informed consent form before performing any study procedures.
12. Compliance to study procedures.

Exclusion Criteria:

1. monoclonal antibody therapy within 4 weeks prior to first dose; CAR-T therapy within 3 months prior to first dose; or other anti-myeloma therapy within 2 weeks prior to first dose.
2. Only Arm B:intolerance to lenalidomide.
3. Plasma cell leukemia, non-secretory multiple myeloma, Fahrenheit macroglobulinemia, primary amyloidosis, POEMS syndrome.
4. Subjects planning to undergo a stem cell transplant prior to progression of disease on this study, i.e., these subjects should not be enrolled in order to reduce disease burden prior to transplant.
5. Subject has previously received an allogenic stem cell transplant (regardless of timing).
6. Participated in other clinical trial treatments within 14 days before the first dose (calculated from the time of withdrawal from the study treatment).
7. Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function.
8. Known central nervous system involvement.
9. Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior treatment.
10. Not recovered from recent surgical procedures based on investigator's discretion. Major surgical procedure within ≤28 days or minor surgical procedure within ≤14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment and 14 days post last treatment, radiotherapy ≤14 days.
11. Unstable angina, myocardial infarction, or coronary revascularization within 180 days prior to the first dose.
12. Active rheumatoid arthritis, active inflammatory bowel disease, or other chronic inflammatory diseases.
13. Active infection need systemic treatment, including HIV antibody positive, HCV Ab or RNA more than ULN, or HBV-DNA more than ULN.
14. Severe uncontrollable medical condition, including, but not limited to, symptomatic congestive heart failure, severe arrhythmias, unstable angina, or a psychiatric disorder that may affect study adherence;
15. Subject has any concurrent or recent malignancy ≤ 5 year prior to registration with the exception of: basal or squamous cell skin cancer and any carcinoma in situ with adequate therapy, or other cancers successfully cured with surgical procedures or drugs ≥ 2 years.
16. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
17. Female patients who are pregnant or breastfeeding.
18. Requires treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer、strong CYP2C8 inhibitor (except study treatment).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (Single agent); Dose escalation APG-2575 at 3 dose levels 3+3 design.	Drug: APG-2575; APG-2575 orally once daily, every 28 days as a cycle.
Experimental: Arm B (combo); Dose escalation APG-2575 at 3 dose levels in combination with Rd, 3+3 design.	Drug: APG-2575; APG-2575 orally once daily, every 28 days as a cycle.; Drug: Rd; Lenalidomide administered at a dose of 25 mg orally (PO) on Days 1 through 21 of each 28-day cycle, dexamethasone administered at a dose of 40 mg (or 20 mg for patients>75 years old) on Days 1, 8, 15, and 22 of a repeated 28-day cycle.; Other Names: Lenalidomide +Dexamethasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity	DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 28 days of study treatment. These will be assessed via CTCAE version 5.0.	28 days

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Investigators: Study Chair: Yifan Zhai, MD, PhD, Suzhou Yasheng Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2021
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 5, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Multiple myeloma; APG-2575; Bcl-2 inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide
• Other Study ID Numbers: APG2575MC101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No