Sign Up Now!
To sign up for our newsletter or print publications, please enter your contact information below.
First Name *
Last Name *
Email Address (Verify) *
We will request your mailing address on the next page.
We will request your mailing address on the next page.

Teclistamab, a BCMA x CD3 Bispecific Antibody, in Patients with RRMM: Phase 1 Study Updates

Conference Correspondent  - ASH Highlights

Favorable results from a phase 1 study were previously presented for intravenously administered teclistamab (JNJ-7957), a B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (RRMM). The primary objective was to identify the dose(s) to be used in the phase 2 investigation. Updated results and data for subcutaneous administration are now available.

A total of 84 and 65 patients received intravenous (IV; 0.3-720 μg/kg) and subcutaneous (SC; 80-3000 μg/kg) teclistamab, respectively. The median age was 63 years, and the median number of prior lines of therapy was 6. Whereas 96% and 81% of patients were triple-class exposed/refractory, 69% and 39% of patients were penta-drug exposed/refractory, and 91% of patients were refractory to their last line of therapy.

Regarding pharmacokinetics, the half-life of teclistamab supports weekly IV dosing. Following weekly IV or SC treatment, exposures increased in a dose-related manner. An SC dose of 1500 μg/kg had a comparable maximum serum concentration (Cmax) to an IV dose of 270 μg/kg, but higher trough levels versus a 720-μg/kg IV dose. Time to reach Cmax following SC dosing ranged from 3 to 8 days.

The most common hematologic adverse events (AEs) were anemia (55%), neutropenia (57%), thrombocytopenia (40%), and leukopenia (28%), whereas the most common nonhematologic AEs were cytokine release syndrome (CRS; 55%), pyrexia (30%), diarrhea (23%), cough (21%), fatigue (22%), nausea (22%), and headache (22%). Grade ≥3 AEs occurred in 39% of patients; neutropenia (18%) and anemia (12%) were the most common. CRS (any grade) developed in 54% and 57% of patients with IV and SC dosing, respectively; events were observed within a median of 1 day after SC administration. All CRS events were grade 1/2 and tended to occur with the initial 1 to 2 dose(s). Among patients who received IV administration, 5% of patients experienced neurotoxicity (2 AEs being grade ≥3), 5% of patients experienced treatment-related infusion-related reactions (all grade 1/2), and grade 5 AEs were reported in 4 patients but were deemed unrelated to treatment by the investigator, with the exception of 1 case of pneumonia. Injection-site reactions were experienced by 22% of patients who received SC administration (all grade 1/2). Grade ≥3 infection-related AEs were observed in 15% of patients. The maximum tolerated dose has not been reached.

The overall response rate among the 120 patients with evaluable data across 4 IV and SC dose-level ranges (IV, 270-720 μg/kg weekly; SC, 720-1500 μg/kg weekly) was 69% (47 of 68 patients specifically included in the response analysis, including 40 with very good partial response or better [≥VGPR] and 18 with complete response or better [≥CR]). Although response data for patients who received a 3000-μg/kg SC dose are not yet available, the 1500-μg/kg SC dose was selected for phase 2 investigation and 15 of 16 patients on this dose continue to be in response (3 partial response, 5 VGPR, 4 CR, and 3 stringent CR), with responses deepening over time. The median time to first response among 35 patients with responses in the SC cohort was 1 month, whereas 32 responding patients remain on therapy for 1.7 months to 14 months after a median follow-up of 6.5 months. Among patients in CR evaluable for minimal residual disease (MRD), 5 of 5 patients across the IV and SC cohorts have sustained MRD-negativity at 10–6.

Favorable efficacy and safety results from this updated analysis of a phase 1 study support the planned phase 2 monotherapy trial of teclistamab 1500 μg/kg administered subcutaneously in patients with RRMM.


Reference

Abstract 180. ASH 2020. December 5, 2020. Updated Phase 1 Results of Teclistamab, a B-Cell Maturation Antigen (BCMA) x CD3 Bispecific Antibody, in Relapsed and/or Refractory Multiple Myeloma (RRMM).

Related Items
Pevonedistat plus Azacitidine Improves Outcomes versus Azacitidine Monotherapy in High-Risk MDS
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Myelodysplastic Syndromes
Ruxolitinib in Graft-versus-Host Disease: Practice-Changing Results
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Graft-versus-Host-Disease
Step-Up Glofitamab Dosing Induces High Response Rates in Relapsed or Refractory Non-Hodgkin Lymphoma
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Clinical Trials, Lymphoma
ZUMA-12: Axicabtagene Ciloleucel Shows Substantial Benefit in High-Risk Large B-Cell Lymphoma
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, CAR T-Cell Therapy, Lymphoma
Momelotinib, a Novel JAK Inhibitor, Makes Inroads in Intermediate- or High-Risk Myelofibrosis
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Myelofibrosis, Novel Pharmaceuticals
Oral Vodobatinib Elicits Durable Responses in Heavily Pretreated Patients with Chronic Myeloid Leukemia
JHOP - February 2021 Vol 11, No 1 published on February 22, 2021 in ASH Highlights, Leukemia, Novel Pharmaceuticals
A Phase 2 Study of Isatuximab for Patients with Previously Treated AL Amyloidosis
Conference Correspondent  published on December 9, 2020 in ASH Highlights
VRD Consolidation Followed by Lenalidomide Maintenance versus Maintenance Alone in Transplant-Eligible Patients with NDMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
A Dose-Finding Study of Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone for RRMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
Phase 2 GRIFFIN Study Update: Daratumumab + Lenalidomide, Bortezomib, and Dexamethasone in Transplant-Eligible NDMM
Conference Correspondent  published on December 9, 2020 in ASH Highlights
Copyright © Green Hill Healthcare Communications, LLC. All rights reserved.