Optec/Optal: A phase 2 study to evaluate outpatient (OP), step-up administration of teclistamab (Tec) or talquetamab (Tal) with prophylactic tocilizumab (prophyToci) in patients (pts) with relapsed/refractory multiple myeloma (RRMM).

Abstract

7510 Background: Tec, a B-cell maturation antigen x CD3 bispecific antibody (bsAb), and Tal, a G protein-coupled receptor class C group 5 member D x CD3 bsAb, are approved for the treatment of pts with triple-class exposed (TCE) RRMM. Cytokine release syndrome (CRS) is a common adverse event associated with T-cell therapies. CRS occurred in 72% and 73-79% of pts in the MajesTEC-1 (TEC-1) and MonumenTAL-1 (TAL-1) studies, respectively. One cohort of pts in TEC-1 received prophyToci, resulting in a lower rate of CRS (26%) without negatively impacting safety or efficacy. A cohort of pts in TAL-1 received prophyToci, with 18% experiencing CRS; safety and efficacy were comparable to the overall TAL-1 population. Methods: This nonrandomized, multicenter, prospective study evaluates prophyToci in RRMM pts treated with Tec (Arm A) or Tal (Arm B) using the approved step-up dose (SUD) schedule in the OP setting. ProphyToci 8 mg/kg was administered before SUD 1 of either Tec or Tal. Specific recommendations (home monitoring, IV immunoglobulin [IVIG] for IgG levels <400 mg/dL) and restrictions (caregiver requirements and travel distance) are also provided for pt safety. Primary endpoint is incidence of any grade CRS in cycles 1-2. Secondary endpoints include safety and efficacy measures. Safety parameters encompass incidence of Grade ≥2 CRS, any grade recurrent CRS, any grade infections, neurotoxicity (NT), and neutropenia throughout the study. Efficacy endpoints include overall response rate (ORR), best overall response (BOR) and progression-free survival (PFS). Results: As of 06 January 2026, 43 pts enrolled in Arm A, and 7, in Arm B. In Arm A, the CRS rate was 5%, all G1. In Arm B, G1 CRS occurred in 14% of pts. Adverse events G≥3 included neutropenia (G3, n=4; G4, n=6), anemia (G3, n=1), and febrile neutropenia (G3, n=1). Twenty pts (47%) in Arm A experienced infections, with 19% ≥G3. Among Arm A patients who experienced infections, 10 (50%) exhibited IgG levels <400 mg/dL, of whom 2 (20%) received IVIG. In Arm B, 4 pts (57%) experienced infections, with 29% (n=2) ≥G3. BOR in Arm A included 3 stringent complete responses (sCRs), 6 CRs, 11 very good partial responses (VGPR), 8 PRs, 1 stable disease, 5 progressive disease (PD), and 9 non-evaluable pts. Among the 34 evaluable pts in Arm A, the ORR was 82%. BOR in Arm B included 1 sCR and 6 non-evaluable pts. After a median follow-up of 11.8 months, 74.4% of pts (n=32) in Arm A did not experience progression. Conclusions: A single dose of prophyToci before SUD 1 of Tec or Tal reduced the incidence of CRS, with no impact on safety or efficacy, and supports administration of these bsAbs in the OP setting. The protocol was amended to add an arm evaluating the effect of prophylactic oral dexamethasone on CRS in pts treated with Tec (Arm C). Enrollment is ongoing (NCT05972135). Clinical trial information: NCT05972135 .