Phase 1/2 Open‑Label Study of Oral Surzetoclax Monotherapy and Surzetoclax plus Etentamig Combination in Relapsed/Refractory Biomarker‑Selected Multiple Myeloma

Primary objective:

• Characterize the safety, toxicity, and tolerability of surzetoclax in combination with etentamig in biomarker‑selected subjects with relapsed or refractory Multiple Myeloma.
• Determine the recommended dose(s) of surzetoclax and etentamig when administered together in this population.

• Evaluate the preliminary antimyeloma efficacy of the combination.
• Characterize the pharmacokinetic profile of etentamig and its immunogenicity when co‑administered with surzetoclax.
• Characterize the pharmacokinetic profile of surzetoclax when given with etentamig.

The trial enrolled 43 subjects diagnosed with relapsed or refractory Multiple Myeloma. Both male and female participants were included, representing the age categories indicated by codes 3 and 4, which correspond to adult age groups. Eligibility required an ECOG performance status of 0 or 1, centrally confirmed t(11;14) positive and/or BCL2high status, and documented disease progression per IMWG 2016 criteria after the most recent treatment regimen. All enrolled individuals were classified as patients with relapsed or refractory disease.

The study is a Phase 1/2, open‑label, platform trial evaluating the safety, tolerability, and preliminary efficacy of the BCL‑2 inhibitor Surzetoclax administered orally as monotherapy or in combination with the intravenous agent Etentamig in adult subjects with relapsed or refractory multiple myeloma. Participants are enrolled following a screening visit that confirms disease status, ECOG performance (0‑1), and central determination of t(11;14) and/or BCL2‑high biomarker positivity. After eligibility confirmation, a baseline visit initiates treatment and pharmacokinetic sampling. Subsequent study visits occur every 28 days to assess dose‑limiting toxicities, adverse events, response per IMWG criteria, and laboratory parameters; additional visits are scheduled for disease‑assessment imaging and minimal residual disease testing. The treatment period may extend up to 12 months, after which an end‑of‑study visit captures final efficacy and safety outcomes. Early termination may occur for occurrence of a dose‑limiting toxicity, disease progression, withdrawal of consent, or investigator‑determined unacceptable toxicity. The overall trial recruitment window spans from July 2026 to January 2031, with each participant remaining in the study for the duration of treatment plus the final follow‑up visit.

The investigational oral agent Surzetoclax is supplied as a film‑coated tablet. It is administered by the oral route. The specific dose and dose unit are defined in the study protocol, and the tablet is taken according to the designated dosing schedule, typically once daily.

The investigational intravenous agent Etentamig is provided as a solution for infusion. It is administered by intravenous infusion. The exact dose, dose unit, and infusion frequency are outlined in the protocol and are administered on the schedule required for combination therapy with Surzetoclax.

No non‑experimental comparator, placebo, or standard‑of‑care therapy is incorporated into this trial; participants receive only the investigational agents as described.

Drug administration is recorded in the case report form. Compliance with oral Surzetoclax is assessed by pill count and patient diary. Infusion of Etentamig is documented by infusion logs and vital sign monitoring. Dosing adjustments follow predefined safety criteria.

Efficacy will be evaluated using a set of secondary endpoints that include Overall Response Rate (ORR), Progression‑Free Survival (PFS), Duration of Response (DOR), Time‑to‑Progression (TTP), Time to Next Treatment, overall survival (OS), and the rate of minimal residual disease (MRD) negativity as determined centrally.

Response assessments will be performed according to standard disease‑specific criteria, and MRD status will be measured with Adaptive’s clonoSEQ next‑generation sequencing assay. All efficacy parameters will be collected and analyzed throughout the study period in accordance with the protocol‑defined statistical analysis plan.