OPTec: A phase 2 study to evaluate outpatient (OP) step-up administration of teclistamab (Tec), a BCMA-targeting bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Authors: Rifkin Robert M. , Schade Henning Helmut , Simmons Gary , Yasenchak Christopher A. , Fowler Jessica , Lin Thomas S. , Thomson Brian , Xu Weiming 
Published: June 2024

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Background: Tec is the only approved BCMA×CD3 bispecific antibody with personalized, weight-based dosing for triple-class exposed RRMM. In the MajesTEC-1 study, Tec showed deep, durable responses and a manageable safety profile. Cytokine release syndrome (CRS) occurred in 72% of pts during Cycles 1-2, and 33% of pts had recurrent CRS grade (gr) ≤3 (gr 3, 0.6%). Tocilizumab (Toci) is used to manage CRS. 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 OP setting may make Tec more accessible, especially at community centers. Therefore, we are investigating whether proToci can reduce the incidence and severity of CRS associated with Tec and facilitate safe OP administration. Methods: This single-arm, non-randomized, multicenter, prospective study (NCT05972135) will evaluate proToci in pts treated with Tec using an OP SUD regimen. The primary endpoint is the overall incidence of CRS. Secondary endpoints include recurrent CRS gr ≥3, and any gr infections, neurotoxicity (NT) including ICANS, neutropenia, and efficacy. Eligible pts are ≥18 years with RRMM and ≥4 prior lines of therapy. Pts with rapidly progressing MM, CNS involvement, active infection, or contraindication to Toci are excluded. Toci 8 mg/kg IV is administered 2 to 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 ≥PR after 6 mo can receive 1.5 mg/kg SC biweekly. IVIG is allowed in pts with serum IgG <400 mg/dL. Results: Ten pts will be enrolled at 4 Sarah Cannon / US Oncology community sites in a safety and PK/PD cohort, followed by 40 pts at 12 sites. After the first 6 pts, a Data Review Committee (DRC) meeting was held. Median age was 74 (56 to 83) yrs; half of pts were male. Pts had received a median of 4.5 (4 to 6) prior therapies. One pt with diffuse bony lesions had an SAE of bilateral leg weakness and pain unrelated to Toci or Tec, did not complete the SUD regimen, and died on C1D40 of unknown causes. The other 5 pts completed the SUD regimen per protocol. AEs in >1 pt were fatigue, headache and neutropenia (2 each). Gr 2 hypotension (1 pt) and gr 1 confusion and dizziness (1 pt each) were not felt due to CRS or ICANS. Stopping criteria (gr >3 CRS or NT/ICANS) were not met. The DRC recommended proceeding with enrollment. Conclusions: Initial results indicate that proToci prior to SUD 1 of Tec may mitigate the risk of CRS. Enrollment is ongoing to determine if proToci may make Tec safe to give in an OP setting and increase accessibility in community centers. The full safety cohort will be presented at ASCO. Clinical trial information: NCT05972135 .