APG-2575 Combinations for Multiple Myeloma

Not currently recruiting at 2 trial locations

Overseen By Angela Kaiser

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ascentage Pharma Group Inc.

Must not be taking: BCL-2 therapy, CYP3A inhibitors

Disqualifiers: Infections, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a new drug combination, APG-2575 (Lisaftoclax), for patients with multiple myeloma that has returned or not responded to previous treatments. It tests two combinations: one with pomalidomide and dexamethasone, and another with lenalidomide and dexamethasone. The trial suits individuals treated for multiple myeloma between one and four times before, whose disease continues to progress. Participants should have multiple myeloma that didn't respond to recent treatments. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group. It offers participants a chance to contribute to the early-stage development of potentially beneficial therapies.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you require treatment with a strong cytochrome P450 (CYP) 3A inhibitor or have received antineoplastic therapy within 2 weeks before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, 69.4% of patients taking APG-2575, also known as lisaftoclax, reported mostly mild side effects. Another study showed that combining lisaftoclax with pomalidomide and dexamethasone was generally safe, with serious side effects being rare, even at higher doses. This suggests the treatment is usually well-tolerated. Additionally, research has found that lisaftoclax was well-tolerated and showed early signs of effectiveness in patients with other related conditions. This provides some confidence that lisaftoclax might be safe for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about APG-2575 for multiple myeloma because it works differently than standard treatments. Most existing therapies target general cancer cell growth, but APG-2575 specifically targets and blocks a protein called BCL-2, essential for cancer cell survival. This targeted approach may lead to fewer side effects and improved effectiveness. Additionally, when combined with Pomalidomide or Lenalidomide and dexamethasone, APG-2575 has the potential to enhance treatment outcomes by attacking the cancer cells from multiple angles.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that APG-2575 could be effective when combined with other drugs to treat relapsed or refractory multiple myeloma. In this trial, one treatment arm combines APG-2575 with pomalidomide and dexamethasone, significantly reducing cancer signs in 63.9% of patients. This combination is also considered safe, even at higher doses. Another treatment arm involves APG-2575 with lenalidomide and dexamethasone. Although research is ongoing for this combination, early results suggest it is safe and may be effective. These drug combinations aim to improve patient outcomes by more effectively targeting cancer cells. ^{2 6 7 8 9}

Who Is on the Research Team?

Yifan Zhai, MD, PhD

Principal Investigator

Ascentage Pharma Group Inc.

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory multiple myeloma who have had 1-4 prior treatments. They must have good liver and kidney function, a life expectancy of at least 6 months, and be able to perform daily activities with some limitations (ECOG ≤ 2). Women must not be pregnant and all participants should agree to use effective birth control.

Inclusion Criteria

Ability to complete questionnaire(s) by themselves or with assistance (For AL amyloidosis patients only)

I have AL amyloidosis, have had treatment before, and my disease can be measured.

I have MM, treated 1-4 times before, and my condition worsened quickly after the last treatment.

Exclusion Criteria

I have plasma cell leukemia or a similar condition.

I have newly diagnosed multiple myeloma and have had minimal or no treatment.

I have AL amyloidosis and haven't received systemic therapy or have it with multiple myeloma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive APG-2575 in combination with Pd to determine the MTD and RP2D using a 3+3 design

28 days per cycle

Multiple visits per cycle for dose escalation monitoring

Dose Expansion

Participants receive APG-2575 at the determined RP2D to further evaluate safety and efficacy

28 days per cycle

Regular visits per cycle for safety and efficacy assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• APG-2575

Trial Overview The study tests APG-2575 in combination with two other drug regimens (DRd or Pd) on patients whose multiple myeloma has returned or didn't respond after treatment. It's an early-phase trial that includes increasing doses to find safe levels before expanding the number of patients.

How Is the Trial Designed?

Group I: APG-2575+LD Experimental Treatment 1 Intervention

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

Group II: APG-2575 +Pd or LD Experimental Treatment 1 Intervention

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

APG-2575 is already approved in China, United States for the following indications:

Approved in China as Lisaftoclax for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

Approved in United States as Lisaftoclax for:

• None approved yet; under investigation for CLL/SLL, Waldenström macroglobulinemia, multiple myeloma, and acute myeloid leukemia

Who Is Running the Clinical Trial?

Ascentage Pharma Group Inc.

Lead Sponsor

Trials

54

Recruited

5,700+

Citations

1. ashpublications.org ashpublications.org/blood/article/138/Supplement%201/4764/481763/Trial-in-Progress-Phase-1b-2-Open-Label-Study-of

Trial in Progress: Phase 1b/2 Open-Label Study of Lisaftoclax ... Trial in Progress: Phase 1b/2 Open-Label Study of Lisaftoclax (APG-2575) Monotherapy or in Combination with Lenalidomide/Dexamethasone in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121066611

Phase 1b/2 Open-Label Study of Lisaftoclax (APG-2575) ... This open-label, multicenter study is assessing the safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of lisaftoclax alone or ...

3. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper202713.html

1022 Lisaftoclax (APG-2575) Combined with Novel ... This study evaluated the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Pd; Arm A) or daratumumab, ...

4. targetedonc.com targetedonc.com/view/lisaftoclax-plus-pd-demonstrates-strong-response-and-safety-in-rrmm

Lisaftoclax Plus Pd Demonstrates Strong Response and ... The combination of lisaftoclax (APG-2575) plus pomalidomide (Pomalyst) and dexamethasone (Pd) showed favorable overall response rate (ORR), ...

5. ascentage.com ascentage.com/live-from-eha-2024-ascentage-pharma-releases-updated-data-of-lisaftoclax-in-patients-with-r-r-mm-and-al-amyloidosis-highlighting-marked-improvement-in-orr/

Live from EHA 2024 Building on results from the study released for the first time at the 2023 American Society of Hematology Annual Meeting, the updated data ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1022/531476/Lisaftoclax-APG-2575-Combined-with-Novel

Lisaftoclax (APG-2575) Combined with Novel Therapeutic ... Among 49 pts in the safety population, 34 (69.4%) reported any-grade lisaftoclax treatment-related AEs (TRAEs; ≥ 5% incidence), including ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10330157/

Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory ... This global phase 1 trial investigated the safety, efficacy, pharmacokinetics, and pharmacodynamics of lisaftoclax (APG-2575), a novel, orally active, potent ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123086196

First Report on the Effects of Lisaftoclax (APG-2575) in ... Lisaftoclax, combined with novel therapeutic regimens, was well tolerated and has demonstrated preliminary antitumor activity in patients with AL amyloidosis ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03537482

APG-2575 Study of Safety, Tolerability ,PK/PD in Patients ... Age ≥18 years old. Histologically confirmed diagnosis of either one of the B-cell hematologic malignancies including multiple myeloma, chronic lymphocytic ...