A Study to Assess Adverse Events and Change in Disease Activity of Oral Surzetoclax Alone or in Combination With Subcutaneous and/or Oral Antimyeloma Agents in Adult Participants With Multiple Myeloma (MM)

Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and change in disease activity of surzetoclax in adult participants with relapsed/refractory (R/R) MM. Adverse events and change in disease activity will be assessed. Surzetoclax is an investigational drug being developed for the treatment of R/R MM. In Substudy 1 there will be dose escalation and dose expansion phases where participants will receive various doses (escalation) or 1 of 2 doses (expansion) of surzetoclax in combination with daratumumab + dexamethasone, to determine the best dose of surzetoclax. In Substudy 2, there will be a dose escalation phase where participants will receive various doses of surzetoclax alone. In Substudy 3 there will be dose escalation and optimization phases where participants will receive various doses (escalation) or 1 of 2 doses (optimization) of of surzetoclax and etentamig to determine the best dose of surzetoclax and etentamig. Optimization will also include etentamig received alone. Approximately 325 adult participants with R/R MM will be enrolled in the study in approximately 55 sites worldwide. In Substudy 1 escalation phase, participants will receive oral surzetoclax tablets in combination with subcutaneous (SC) daratumumab injections + oral dexamethasone tablets and in the expansion phase, will receive 1 of 2 doses oral surzetoclax tablets in combination with SC daratumumab injections + oral dexamethasone tablets or daratumumab injections + oral pomalidomide + oral dexamethasone tablets. In Substudy 2, Japanese participants will receive oral surzetoclax tablets. In Substudy 3 escalation phase, participants will receive oral surzetoclax tablets in combination with IV etentamig and in the expansion phase, will receive 1 of 2 doses of both oral surzetoclax tablets in combination with of IV etentamig, or IV etentamig alone. The total study duration is approximately 4.5 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution. The effect of the treatment will be frequently checked by medical assessments, blood tests, and side effects.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Documented diagnosis of multiple myeloma (MM) based on standard international myeloma working group (IMWG) diagnostic criteria.
* All participants must have measurable disease per central laboratory with at least 1 of the following assessed within 28 days prior to enrollment:

  * Serum M-protein \>= 0.5 g/dL (\>= 5g/L); OR
  * Urine M-protein \>= 200 mg/24 hours; OR
  * For participants without measurable serum and urine M-protein: Serum free light chain (sFLC) \>= 10 mg/dL (100 mg/L), provided sFLC ratio is abnormal.
* B-cell lymphoma (BCL)-2 inhibitor treatment naïve.
* t(11;14) positive status and/or BCL2 high status.
* Must have confirmed diagnosis of relapsed or refractory (R/R) multiple myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen, based on the investigator's determination of the international myeloma working group (IMWG) 2016 criteria.

Exclusion Criteria:

* Major surgery within 4 weeks of study treatment or planned during study participation.
* Recent infection requiring systemic treatment that was completed \<= 14 days before first dose of study treatment and/or uncontrolled active systemic infection.