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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04674514
• Other study ID #: APG2575MC101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 13, 2021
• Est. completion date: May 2024

Study information

• Verified date: March 2023
• Source: Ascentage Pharma Group Inc.
• Contact: Jianping Ning
• Phone: +86-010-67091790
• Email: jianping.ning[@]ascentage.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: May 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• APG-2575
APG-2575 orally once daily, every 28 days as a cycle.
• 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.

Locations

Country	Name	City	State
China	Beijing Chao-yang Hospital of Capital Medical University	Beijing	Beijing
China	Guangdong Province People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affilated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	People's hospital of Jiangsu Province	Nanjing	Jiangsu
China	Shenzhen Second People's Hospital	Shenzhen	Guangdong
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Union Hospital Tongji Medical College of Huazhong University of Science ang Technology	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Ascentage Pharma Group Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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