Johnson & Johnson (J&J) has reported results from its Phase I studies investigating talquetamab as a monotherapy and in combination with other drugs in patients with relapsed or refractory multiple myeloma (RRMM).The data was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The RedirecTT-1 (NCT04586426) study is an ongoing Phase Ib dose escalation study of the combination of the bispecific T-cell redirection antibodies Tecvayli, BCMAxCD3 bispecific antibody, and talquetamab, GPRC5D bispecific antibody in patients with RRMM.

The results reported a high overall response rate (ORR) among patients with RRMM. The combination therapy reported an ORR of 86.6 percent (71/82) across all dose levels, and an ORR of 96.3 percent (26/27) among patients receiving the recommended Phase II regimen (RP2R).

Results from the study showed that responses were high across all dose levels. The ORR across all patients was 86.6 percent. Patients who received the RP2R achieved an ORR of 96.3 percent.

The median duration of response was not reached in the overall study population. The safety profile of the combination was consistent with that observed with each drug as a monotherapy.

According to Janssen, these results underscore the potential combinability of these two novel bispecific therapies, which target distinct antigens on myeloma cells.

In the study, 94.1 percent of patients at the RP2R and 96.8 percent of the overall study population had one or more treatment-emergent adverse events (TEAEs). The incidence and severity of CRS were consistent with Tecvayli and talquetamab monotherapy treatment.

Talquetamab monotherapy

MonumenTAL-1 (Phase I: NCT03399799, Phase II: NCT04634552), is a Phase I/II single-arm, open-label, multicohort, multicentre dose-escalation study to evaluate the safety and efficacy of talquetamab in adults with RRMM who received three or more prior lines of therapy.

Patients in the study were treated with subcutaneous (SC) talquetamab at the RP2D of 0.8 mg/kg biweekly (Q2W) or 0.4 mg/kg weekly (QW) with step-up doses.

ORR to talquetamab was similar across both doses.

With a median follow-up of 18.8 months, 74.1 percent (106/143) of response-evaluable patients treated with the 0.4 mg/kg QW dose achieved a response, 59.4 percent achieved a VGPR or better, 9.8 percent achieved a CR, and 23.8 percent achieved a stringent CR.

The 12-month overall survival (OS) rates were 77.4 percent, 76.4 percent, and 62.9 percent in the 0.8 mg/kg Q2W dose, 0.4 mg/kg QW dose, and prior T-cell redirection cohorts, respectively.

Study results showed a low discontinuation rate due to adverse events (AEs). No new safety signals were observed with longer term follow-up.

Patients treated with talquetamab, which targets GPRC5D, an antigen uniquely expressed on plasma cells, showed effective myeloma control with concurrent preservation of humoral immune function (i.e., antibody response by B-cells) and recovery of low blood cell counts, distinguishing talquetamab as an important emerging therapy for RRMM.

According to Janssen, the study results suggest the incidence of infection was less frequent with talquetamab compared with data from studies of B-cell maturation antigen (BCMA)-targeted T-cell–based therapies.

Talquetamab combination with Darxalex faspro

The TRIMM-2 (NCT04108195) study is an ongoing Phase 2 study of Darzalex faspro  (daratumumab and hyaluronidase-fihj) regimens in combination with talquetamab for the treatment of patients with multiple myeloma, who have received a minimum of three prior lines of therapy.

Median DOR was 20.3 months in the 0.8 mg/kg Q2W arm and was not reached in the 0.4 mg/kg QW arm.

Median OS was not reached in either arm. The safety profile was clinically manageable and no new safety signals were observed with longer term follow-up.

“With an overall response rate of nearly 80 percent, this durable combination provides the potential for significant disease control and survival in heavily pre-treated patients with relapsed or refractory multiple myeloma,” said Dr Bhagirathbhai Dholaria, the study’s principal investigator.

GlobalData’s analyst consensus forecast, J&J’s Tecvayli is to be a blockbuster agent, with predicted sales of $2.6 billion in 2028.

GlobalData is the parent company of Clinical Trials Arena.