Optec: A Phase 2 Study to Evaluate Outpatient Step-up Administration of Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results

Background: Teclistamab (tec) is the first approved B-cell maturation antigen (BCMA) × CD3 bispecific antibody (BsAb) for the treatment of patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM), with weight-based dosing and the longest study follow-up of any bispecific antibody in MM. In the phase 1/2 MajesTEC-1 study (NCT03145181/NCT04557098) in patients with heavily pretreated RRMM, rapid, deep, and durable responses were observed over a median follow-up of 30.4 months, with a manageable safety profile. Cytokine release syndrome (CRS) occurred in 72% of pts and 33% of pts had > 1 CRS event (grade [gr] 3, 0.6%); CRS recurrence was reduced when tocilizumab (Toci) was administered for the first CRS event compared with when it was not (20% vs 62%, respectively). In a separate MajesTEC-1 cohort, pts who received prophylactic Toci (proToci) experienced less CRS, compared with pts who did not (26% vs 72%). Administering the tec step-up dosing (SUD) regimen in the outpatient (OP) setting may make tec more accessible to patients, especially in the community setting. The OPTec study aims to investigate whether proToci can reduce the incidence and severity of CRS associated with tec and facilitate safe outpatient (OP) administration in clinical practice. Here, we present updated results from the OPTec study. Methods: This single-arm, non-randomized, multicenter, prospective study (NCT05972135) evaluates proToci in pts treated with tec using an OP SUD regimen. Eligible patients were ≥18 years of age with TCE RRMM and ≥4 prior lines of therapy. Toci 8 mg/kg was administered intravenously (IV) 2-4 hours prior to SUD 1 of tec in an OP setting. The tec SUD regimen consists of 0.06 mg/kg subcutaneously (SC), 0.3 mg/kg SC 2 to 4 days later, and 1.5 mg/kg SC 1 week after SUD 1. tec 1.5 mg/kg SC is then given weekly for 12 cycles (28-day) or until MM progression or unacceptable toxicity. Pts with partial response or better (≥PR) after 6 months can receive 1.5 mg/kg SC biweekly. Intravenous immunoglobulin (IVIG) is suggested in pts with serum IgG <400 mg/dL. The primary endpoint is the overall incidence of CRS. Secondary endpoints include recurrent CRS gr ≥3, any gr infections, and neurotoxicity (NT), including immune effector cell-associated neurotoxicity syndrome (ICANS), neutropenia, and efficacy. Results: To date, 13 pts have been enrolled at 12 Sarah Cannon/US Oncology community sites. One pt developed diffuse bony lesions, weakness and pain due to rapidly progressing MM, did not complete the SUD regimen, and died on C1D40. Eleven pts have completed the SUD regimen per protocol and are included in the safety analysis. Median age was 70 (53-83) yrs; 5 pts were male; 6 pts were female, 1 Black, 6 White, 3 unknown, and 1 unreported. Pts had received a median of 4 (range, 4 to 6) prior lines of therapy. Hematologic adverse events (AEs) included neutropenia (1 pt gr 3, 3 pts gr 4) and lymphopenia (2 pts gr 1). No patients experienced febrile neutropenia. To date, no pts experienced CRS or ICANS or required hospitalization due to tec or Toci. A total of 7 infections, all gr 2, occurred in 4 pts. Seven pts developed IgG < 400 mg/dL, of whom 6 received IVIG replacement. Other AEs in >1 pt were fatigue, headache, and injection site reactions. Gr 2 hypotension (2 pts) was not attributed to CRS. Stopping criteria (gr > 3 CRS or NT/ICANS were not met. Seven pts are evaluable for clinical response (7/11); all 7 responded, achieving a complete response (CR) (n=1), very good partial response (VGPR) (n=5), or partial response (PR) (n=1). All 11 pts who have completed the SUD remain on study. Enrollment is ongoing. Conclusion: Initial results from the OPTec study indicate that proToci may reduce the risk of CRS. None of the 11 subjects treated to date have experienced CRS or ICANS, and the safety profile is otherwise comparable to the pivotal MajesTEC-1 results. Enrollment is ongoing to determine if proToci may facilitate OP administration of the tec SUD schedule in an OP setting and increase patient accessibility in community centers. Additional data and follow-up in more pts, including PK data in the first 10 pts in addition to updated infection, IVIG use, and response data will be presented at ASH. The protocol is being amended to add a cohort of Talquetamab to determine if proToci can reduce CRS and facilitate OP SUDs across bispecific antibodies.