The purpose of this study is to evaluate the safety and tolerability of the study drug, APG2575 in combination with Pomalidomide and Dexamethasone for both relapsed/refractory multiple myeloma or light chain amyloidosis patients and in combination with Daratumumab, Lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients. This study will also look at identifying any dose-limiting toxicities and the maximum tolerated dose of APG-2575.

APG-2575 is an oral medication and  targets a specific protein in your body called BCL-2. When you have hematologic malignancies, this BCL-2 protein may build up and prevent cancer cells from self-destructing naturally. APG-2575 targets BCL-2 in order to help restore this self-destructing process.

There are 3 arms, or cohorts, to this study. Depending on your disease, you will be randomized to the following arms and treatment plans.

Arm A: For participants with relapsed and/or refractory multiple myeloma. Participants will take either 400mg, 600mg, or 800mg of APG2575 orally once daily for 28 days, 4mg of pomalidomide orally on Day 1 through 21, and 40 or 20 mg Dexamethasone orally once a week.

Arm B: For participants with relapsed and/or refractory multiple myeloma. Participants will take either 400mg, 600mg, or 800mg of APG2575 orally once daily for 28 days, 25mg of lenalidomide orally on Day 1 through 21, 40 or 20 mg Dexamethasone orally once a week, and 1800 mg daratumumab injection once a week for the first two cycles, then once bi-weekly. 

Arm C: For participants with light chain amyloidosis. Participants will take APG2575 orally once daily for 28 days, 4mg of pomalidomide orally on Day 1 through 21, and 40 or 20 mg Dexamethasone orally once a week.

Each treatment cycle is 28-days. Treatment will be given in repeated 28-day cycles and will continue until either unacceptable toxicity or disease progression, judgement of the treating physician, or participants choose to withdraw consent at any point in the study.