Inclusion Criteria:
1. ≥ 18 years of age. 2. 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).
3. Eastern Cooperative Oncology Group (ECOG) ≤ 2. 4. Life expectancy ≥ 6 months. 5. Adequate hematologic function defined as:
1. ANC ≥1.0 x 10^9/L independent of growth factor support within 7 days of the first
dose with study drug. 2. Hemoglobin ≥8 g/dL without transfusion or growth factor support within 7 days of
the first dose of study drug. 3. Platelet count ≥ 50 x 10^9/L without transfusion support within 7 days of the
first dose of study drug (for MM patients); or platelet count ≥ 100 x 10^9/L or ≥
50 x 10^9/L if bone marrow involvement independent of transfusion support in
either (for AL amyloidosis patients).
6. Adequate hepatic and renal function defined as:
1. AST and ALT < 3 x upper limit of normal (ULN)
2. Creatinine clearance >30 mL/min (for MM patients); or Creatinine ≤3 mg/dL and
CrCL ≥25 ml/min using the Cockcroft-Gault formula (for AL amyloidosis patients)
3. Bilirubin< 1.5 x ULN (Except if considered secondary to Gilbert's syndrome and
primarily indirect bilirubinemia)
7. PT/INR ≤2 x ULN and PTT (or aPTT) ≤2 x ULN. 8. Female subjects who are of non-reproductive potential (i.e., post-menopausal by
history: no menses for ≥2 year; or history of hysterectomy; or history of bilateral
tubal ligation; or history of bilateral oophorectomy). Female subjects of childbearing
potential must have a negative serum pregnancy test upon study entry.
9. Male and female subjects who agree to use highly effective methods of birth control
(e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine
devices[IUDs], sexual abstinence, or sterilized partner) during the period of therapy
and for 90 days after the last dose of study drug. 10. Ability to complete questionnaire(s) by themselves or with assistance (For AL
amyloidosis patients only)
Exclusion Criteria:
1. 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.
2. Subject has received antineoplastic therapy within 2 weeks before the date of
initiating study treatment. 3. Subject has previously received an allogenic stem cell transplant (regardless of
timing)
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. 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).
6. 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. 7. 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. 8. 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. 9. Subject has peripheral neuropathy ≥grade 3 except caused by AL amyloidosis. 10. 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)
11. Plasmapheresis <35 days prior to the initiation of study drug. 12. Failure to have fully recovered (i.e., ≤ Grade 1 toxicity) from the reversible effects
of prior treatment for MM or AL amyloidosis. 13. 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. 14. 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. 15. 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. 16. Recent infection requiring systemic treatment that was completed ≤14 days before the
first dose of study drug. 17. Vaccinated with live, attenuated vaccines within 4 weeks of initiation of APG-2575
(for patients' safety, patients could receive COVID-19 vaccination before or during
study period as judged by HCP as beneficial)
18. Subject has any concurrent or recent malignancy ≤ 1 year prior to registration with
the exception of: basal or squamous cell skin cancer, any carcinoma in situ. NOTE: If
there is a history or prior malignancy, they must not be receiving other specific
treatment for their cancer.
19. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor. 20. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia. 21. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 22. Any other condition or circumstance that would, in the opinion of the investigator,
make the patient unsuitable for participation in the study
