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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04674514
Recruitment Status : Recruiting
First Posted : December 19, 2020
Last Update Posted : March 8, 2022
Sponsor:
Information provided by (Responsible Party):
Ascentage Pharma Group Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: APG-2575 Drug: Rd Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib / II Open-Label Stduy of APG-2575 Monotherapy or in Combination With Lenalidomide / Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : April 13, 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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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 Name: Lenalidomide +Dexamethasone


Outcome Measures
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Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: 28 days ]
    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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04674514


Contacts
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Contact: Jing Yang +86-010-67091790 jyang@ascentagepharma.com
Contact: Wensi Li +86-020-28068500 wensi.li@ascentagepharma.com

Locations
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China, Beijing
Beijing Chao-yang Hospital of Capital Medical University Not yet recruiting
Beijing, Beijing, China, 100020
Contact: Zhongxia Huang, Ph.D         
Principal Investigator: Zhongxia Huang, Ph.D         
China, Guangdong
Sun Yat-sen University Cancer Center Not yet recruiting
Guangzhou, Guangdong, China, 510060
Contact: Zhongjun Xia, Ph.D         
Principal Investigator: Zhongjun Xia, Ph.D         
Guangdong Province People's Hospital Not yet recruiting
Guangzhou, Guangdong, China, 510080
Contact: Jianyu Weng, Ph.D         
Principal Investigator: Jianyu Weng, Ph.D         
The First Affiliated Hospital of Sun Yat-sen University Not yet recruiting
Guangzhou, Guangdong, China, 510080
Contact: Juan Li, Ph.D         
Principal Investigator: Juan Li, Ph.D         
Shenzhen Second People's Hospital Not yet recruiting
Shenzhen, Guangdong, China, 518025
Contact: Xin Du, Ph.D         
Principal Investigator: Xin Du, Ph.D         
China, Henan
Henan Cancer Hospital Not yet recruiting
Zhengzhou, Henan, China, 450003
Contact: Baijun Fang, Ph.D         
Principal Investigator: Baijun Fang, Ph.D         
China, Hubei
Union Hospital Tongji Medical College of Huazhong University of Science ang Technology Not yet recruiting
Wuhan, Hubei, China, 215316
Contact: Mei Hong, Ph.D         
Principal Investigator: Mei Hong, Ph.D         
Zhongnan Hospital of Wuhan University Not yet recruiting
Wuhan, Hubei, China, 430062
Contact: Fuling Zhou, Ph.D         
Principal Investigator: Fuling Zhou, Ph.D         
China, Jiangsu
People's hospital of Jiangsu Province Not yet recruiting
Nanjing, Jiangsu, China, 210029
Contact: Lijuan Chen, Ph.D         
Principal Investigator: Lijuan Chen, Ph.D         
The First Affiliated Hospital of Soochow University Recruiting
Suzhou, Jiangsu, China, 215006
Contact: Zhengzheng Fu, MD.    +86-0512-67781856    fuzhengzheng@suda.edu.cn   
China, Zhejiang
The First Affilated Hospital of Zhejiang University School of Medicine Not yet recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Zhen Cai, Ph.D         
Principal Investigator: Zhen Cai, Ph.D         
The Second Affiliated Hospital of Zhejiang University School of Medicine Not yet recruiting
Hangzhou, Zhejiang, China, 310003
Contact: Wenbin Qian, Ph.D         
Principal Investigator: Wenbin Qian, Ph.D         
Sponsors and Collaborators
Ascentage Pharma Group Inc.
Investigators
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Study Chair: Yifan Zhai, MD, PhD Suzhou Yasheng Pharmaceutical Co., Ltd.
More Information
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Responsible Party: Ascentage Pharma Group Inc.
ClinicalTrials.gov Identifier: NCT04674514    
Other Study ID Numbers: APG2575MC101
First Posted: December 19, 2020    Key Record Dates
Last Update Posted: March 8, 2022
Last Verified: February 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ascentage Pharma Group Inc.:
Multiple myeloma
Bcl-2 inhibitor
APG-2575
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
 Lenalidomide
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents