APG-2575 in Combination With Novel Therapeutic Regimens in Subjects With Relapsed or Refractory Multiple Myeloma

NCT04942067 | Unknown Phase 1 FDA Drug

• 1 other identifier: APG2575MU101
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase Ib/II, open-label, multi-center study evaluating the safety, tolerability, efficacy, and PK/ Pharmacodynamics of APG-2575 in combination with Pd/DRd in patients with relapsed/refractory (RR) multiple myeloma (MM). The study consists of dose escalation and dose expansion phases. The study consists of will start with 2 arms noted below, both arms are independent

Conditions

Multiple Myeloma; Amyloidosis

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  DLT will be defined based on the rate of drug-related grade 3-5 adverse events experienced within the first 6 weeks (2 cycles) of study treatment. These will be assessed via CTCAE version 5.0

  28 days

Study Arms (2)

APG-2575 +Pd or LD

EXPERIMENTAL

APG-2575+ Pomalidomide 4mg QD x 21 days + dexamethasone

Drug: APG-2575+ Pd

APG-2575+LD

EXPERIMENTAL

APG-2575+ Lenalidomide +Dexa Days 1 through 21 of each 28-day cycle,

Drug: APG-2575 + DRd

Interventions

APG-2575+ Pd DRUG

APG-2575 + Pomalidomide 4mg QD x 21 days + dexamethasone (40 mg for patients ≤ 75 years old or 20 mg for patients \> 75 years old) on Days 1, 8, 15, and 22 of a repeated 28-day cycle

Also known as: APG-2575+ Pomalidomide + Dexamethasone

APG-2575 +Pd or LD

APG-2575 + DRd DRUG

APG-2575+ Lenalidomide administered at a dose of 25 mg orally (PO) on Days 1 through 21 of each 28-day cycle, dexamethasone will be administered at a dose of 40 mg (or 20 mg for patients \> 75 years old) once weekly, and daratumumab will be administered intravenously at a dose of 16 mg/kg (or 1800 mg administered subcutaneously if commercially available) weekly in cycles 1 and 2 and then every 2 weeks in cycles 3 to 6 and every 4 weeks thereafter.

Also known as: APG-2575+ Lenalidomide +Dexamethasone+Daratumumab

APG-2575+LD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• MM patients (for Arm A and Arm B): Patients with Relapsed/Refractory MM per 2016 IMWG criteria, previously treated with at least 1 but not more than 4 prior lines of therapy for MM. Refractory MM, meanwhile, is defined as disease that progresses on salvage therapy or progresses within 60 days of the last treatment.
• AL amyloidosis patients (for Arm C ONLY): Patients with AL amyloidosis when meeting:
• i. histochemical diagnosis based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, the type must have been confirmed unequivocally.
• ii. have symptomatic organ involvement. Only purpura and/or carpal tunnel syndrome are not acceptable.
• iii. have at least one prior line of systemic therapy for AL. Patients who do not achieve at least a PR to frontline therapy in 3 months are eligible.
• iv. All MM/AL patients should have measurable disease of AL amyloidosis as defined by at least ONE of the following:
• Serum monoclonal protein ≥1.0 g/dl by protein electrophoresis
• \>200 mg of monoclonal protein in the urine on 24-hour electrophoresis
• Serum differential FLC concentration (dFLC, difference between amyloid forming \[involved\] and nonamyloid forming \[uninvolved\] free light chain \[FLC\]) \> 5 mg/dL; OR serum FLC of 7.5 mg/dL provided the κ/λ FLC ratio is abnormal (κ/λ \<0.26 for patients with monoclonal λ FLC, κ/λ \>1.65 for patients with monoclonal κ FLC).
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy ≥ 6 months
• Adequate hematologic function defined as:
• ANC ≥1.0 x 10\^9/L independent of growth factor support within 7 days of the first dose with study drug
• Hemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of the first dose of study drug

You may not qualify if:

• MM patients with newly diagnosed MM, previously untreated for MM or only had been treated with localized palliative treatment or steroids less than equivalent of dexamethasone 40 mg daily for 4 days). AL amyloidosis patients with AL amyloidosis have not been treated with any systemic therapy, or AL amyloidosis clinically overt multiple myeloma i.e. original CRAB criteria. Extent of marrow plasmacytosis is not prohibitive.
• Subject has received antineoplastic therapy within 2 weeks before the date of initiating study treatment
• Subject has previously received an allogenic stem cell transplant (regardless of timing)
• 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.
• BCL-2-directed therapy within 4 weeks of initiating study treatment. (BCL-2 directed therapy more than 4 weeks before initiation of study treatment is allowed).
• For Arm A/C only: The subjects show evidence of intolerance to pomalidomide, which is defined as subjects discontinued due to any AEs related to prior pomalidomide treatment
• For Arm B only: The subjects show evidence of intolerance to daratumumab or lenalidomide, which is defined as subjects discontinued due to any AEs related to prior daratumumab or lenalidomide treatment
• Patients with any uncontrolled active systemic infection, including but not limited to active hepatitis B or C virus infection, known human immunodeficiency virus (HIV) positive
• Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis
• Subject has plasma cell leukemia (\>2.0\*10\^9/L circulating plasma cells by standard differential) or Waldenström's macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasmapheresis \<35 days prior to the initiation of study drug
• Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects of prior treatment for MM or AL amyloidosis
• Unable to swallow tablets or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia (including Frederica corrected QT interval (QTc) ≥470 msec ) or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to initiating study treatment
• Major 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, radiotherapy ≤14 days prior to initiating study treatment, systemic treatment within 14 days before the first dose of APG-2575

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (3)

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Weil Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

Cleveland Clinic Hosptials

Cleveland, Ohio, 44103, United States

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Amyloidosis

Interventions

Dexamethasone; Lisaftoclax; GTP Cyclohydrolase

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Aminohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Central Study Contacts

Angela Kaiser

CONTACT

301-509-0357; angela.kaiser@ascentage.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: dose escalation and dose expansion after MTD

Study Record Dates

• First Submitted: July 29, 2020
• First Posted: June 28, 2021
• Study Start: December 23, 2021
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 25, 2023

Record last verified: 2023-10

Locations

US (3)