Overview
Phase 1/1b study: Phase 1 Part 1 is a weight-based dose escalation following a 3+3 design of dose-escalating cohorts. Phase 1 Part 2 includes administration at fixed doses. After enrollment, subjects may receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T cells, administered as a single or multiple dose(s). Treated subjects will undergo serial measurements of safety, tolerability and response. Rimiducid may be administered as indicated. Phase 1b of the study will undergo further expansion of cohorts/arms from Phase 1 Parts 1 or 2 or an intermediate dose between cohort levels.
Principal investigator
Eligibility criteria
Inclusion Criteria:
1. Must have signed written, informed consent.
2. Males or females, ≥18 years of age.
3. Must have a confirmed diagnosis of active MM.
4. Must have measurable MM.
5. Must have relapsed / refractory MM, having received treatment with a proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy.
6. Must be willing to practice birth control from the time of Screening and throughout the first year of the study after P-BCMA-ALLO1 administration.
7. Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test within 3 days prior to initiating the lymphodepletion therapy regimen (females of childbearing potential).
8. Must be at least 90 days since autologous stem cell transplant, if performed.
9. Must have adequate vital organ function within pre-determined parameters.
10. Must have recovered from toxicities due to prior therapies.
11. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Exclusion Criteria: 1. Is pregnant or lactating. 2. Has inadequate venous access. 3. Has active hemolytic anemia, plasma cell leukemia, Waldenstrom\'s macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, or amyloidosis. 4. Has an active second malignancy (not disease-free for at least 5 years) in addition to MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma. 5. Has active autoimmune disease. 6. Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc. 7. Has an active systemic infection. 8. Has a history of hepatitis B, hepatitis C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome. Subjects with a history of treated hepatitis C can be enrolled if negative by Hepatitis C PCR on multiple occasions and with medical monitor approval. 9. Is positive for cytomegalovirus (CMV) by PCR, CMV immunoglobulin M (IgM) antibody, or Coronavirus disease 2019 (COVID-19) by PCR. 10. Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia. 11. Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol. 12. Has received prior allogeneic cellular therapy or gene therapy. 13. Has received anti-cancer medications within 2 weeks of the time of initiating conditioning LD therapy. 14. Has received monoclonal antibody therapy within 4 weeks of initiating conditioning LD therapy. 15. Has received immunosuppressive medications within 2 weeks of the time of administration of P-BCMA-ALLO1, and/or expected to require them while on study. 16. Has received systemic corticosteroid therapy within 1 week or 5 half-lives (whichever is shorter) of the administration of P-BCMA-ALLO1 or is expected to require it during the course of the study. 17. Has CNS metastases or symptomatic CNS involvement of their myeloma. 18. Has a history of severe immediate hypersensitivity reaction to any of the agents used in this study. 19. Has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days. 20. Arms R, RS, RP1, RP1.5 and RP2 Only: a) Has received a live vaccine within the last 28 days of the first administration of agents used in Arm R or RS, b) Has any known hypersensitivity or severe reactions or toxicity to agents used in Arms R or RS. 21. Has received radiation within 1 week of initiating conditioning LD therapy.
Exclusion Criteria: 1. Is pregnant or lactating. 2. Has inadequate venous access. 3. Has active hemolytic anemia, plasma cell leukemia, Waldenstrom\'s macroglobulinemia, POEMS syndrome, disseminated intravascular coagulation, leukostasis, or amyloidosis. 4. Has an active second malignancy (not disease-free for at least 5 years) in addition to MM, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma. 5. Has active autoimmune disease. 6. Has a history of significant central nervous system (CNS) disease, such as stroke, epilepsy, etc. 7. Has an active systemic infection. 8. Has a history of hepatitis B, hepatitis C virus, human immunodeficiency virus (HIV), or human T-lymphotropic virus (HTLV) infection, or any immunodeficiency syndrome. Subjects with a history of treated hepatitis C can be enrolled if negative by Hepatitis C PCR on multiple occasions and with medical monitor approval. 9. Is positive for cytomegalovirus (CMV) by PCR, CMV immunoglobulin M (IgM) antibody, or Coronavirus disease 2019 (COVID-19) by PCR. 10. Has New York Heart Association (NYHA) Class III or IV heart failure, unstable angina, or a history of myocardial infarction or significant arrhythmia. 11. Has any psychiatric or medical disorder that would preclude safe participation in and/or adherence to the protocol. 12. Has received prior allogeneic cellular therapy or gene therapy. 13. Has received anti-cancer medications within 2 weeks of the time of initiating conditioning LD therapy. 14. Has received monoclonal antibody therapy within 4 weeks of initiating conditioning LD therapy. 15. Has received immunosuppressive medications within 2 weeks of the time of administration of P-BCMA-ALLO1, and/or expected to require them while on study. 16. Has received systemic corticosteroid therapy within 1 week or 5 half-lives (whichever is shorter) of the administration of P-BCMA-ALLO1 or is expected to require it during the course of the study. 17. Has CNS metastases or symptomatic CNS involvement of their myeloma. 18. Has a history of severe immediate hypersensitivity reaction to any of the agents used in this study. 19. Has a history of having undergone allogeneic stem cell transplantation, or any other allogeneic or xenogeneic transplant, or has undergone autologous transplantation within 90 days. 20. Arms R, RS, RP1, RP1.5 and RP2 Only: a) Has received a live vaccine within the last 28 days of the first administration of agents used in Arm R or RS, b) Has any known hypersensitivity or severe reactions or toxicity to agents used in Arms R or RS. 21. Has received radiation within 1 week of initiating conditioning LD therapy.
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