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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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 8 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. intolerance to lenalidomide. 3. Plasma cell leukemia, non-secretory multiple myeloma, Fahrenheit macroglobulinemia, 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. Participant to other clinical trials within 28 days of first dose. 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. Prior exposure to any BCL-2-directed therapy for MM. 16. 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. 17. Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study. 18. Female patients who are pregnant or breastfeeding. 19. Requires treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer、strong CYP2C8 inhibitor (except study treatment).

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04674514
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ascentage Pharma Group Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Yifan Zhai, MD, PhD
Principal Investigator Affiliation Suzhou Yasheng Pharmaceutical Co., Ltd.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries China
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Additional Details

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.

Arms & Interventions

Arms

Experimental: Arm A (Single agent)

Dose escalation APG-2575 at 3 dose levels 3+3 design.

Experimental: Arm B (combo)

Dose escalation APG-2575 at 3 dose levels in combination with Rd, 3+3 design.

Interventions

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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Suzhou, Jiangsu, China

Status

Recruiting

Address

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006

Site Contact

Zhengzheng Fu, MD.

fuzhengzheng@suda.edu.cn

+86-0512-67781856