Overview

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

Status:
Recruiting
Trial end date:
2024-05-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Ascentage Pharma Group Inc.
Treatments:
Dexamethasone
Lenalidomide
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).