Updated data show 100 percent overall response rate with 56 percent of patients achieving complete response or better with weekly dosing, supporting the combinability of the GPRC5D bispecific antibody
Safety profile, including infection rates, similar to TALVEY® and DARZALEX FASPRO® monotherapies
RIO DE JANEIRO, Sept. 27, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced updated results from the investigational Phase 1b TRIMM-2 study evaluating the combination of TALVEY® (talquetamab-tgvs) with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and pomalidomide in patients with relapsed or refractory multiple myeloma that demonstrated an overall response rate (ORR) of 82 percent, further supporting the investigation of this combination. These data were featured in an oral presentation at the 2024 International Myeloma Society Annual Meeting (Abstract #OA – 01).
The results from the Phase 1b TRIMM-2 study evaluating TALVEY®, the first bispecific T-cell engager to target GPRC5D, combined with DARZALEX FASPRO®, the first subcutaneous anti-CD38 monoclonal antibody, and pomalidomide included patients who received at least three prior lines of therapy, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), or were double refractory to a PI and IMiD and had not received anti-CD38 therapy in the previous 90 days.1
At data cutoff, 77 patients had received TALVEY® in doses of 0.4 mg/kg weekly (QW) or 0.8 mg/kg biweekly (Q2W), with step-up doses, combined with DARZALEX FASPRO® and pomalidomide. In the QW arm (n=18), the overall response rate (ORR) was 100 percent, with 56 percent having a complete response (CR) or better. The Q2W arm (n=59) achieved 76 percent ORR, with 56 percent achieving CR or better. The median duration of response (DOR) in the Q2W arm was 26.4 months, and the median progression-free survival (PFS) was 20.3 months. Results showed 52 percent of patients who are anti-CD38 refractory (n=64) achieved CR or better and 70.8 percent of patients who received prior chimeric antigen receptor T cell (CAR-T) therapy (n=24) achieved CR or better. Patients who had received prior bispecific antibodies (n=29) achieved an 82.8 percent ORR.1
"The deep and durable responses shown in these latest results from TRIMM-2 further support the potential of TALVEY in combination with DARZALEX FASPRO, which has become a standard of care in multiple myeloma, and pomalidomide," said Nizar Bahlis, M.D., Associate Professor, Arnie Charbonneau Cancer Institute, University of Calgary and presenting author.* "With high overall response rates seen across cohorts, this combination shows potential for significant disease control and survival in patients who have received multiple lines of prior therapy, including exposure to prior bispecific antibodies."
The safety profile of this combination reflected the known profiles of TALVEY®, DARZALEX FASPRO® and pomalidomide. Despite the incidence of neutropenia (83.3 percent in the QW arm and 79.7 percent in the Q2W arm) being high, the Grade 3/4 infection rate was generally low (16.7 percent and 37.3 percent, respectively). The majority of on-target, off-tumor treatment-related adverse events (TRAEs), including oral (100 percent in the QW arm, 84.7 percent in Q2W arm), skin (88.9 percent, 67.8 percent), nail (83.3 percent, 55.9 percent) and weight decrease (66.7 percent, 49.2 percent) were low-grade (Grade 1/2) and did not lead to discontinuation of therapy. These results support further investigation of TALVEY® in combination with DARZALEX FASPRO®, with or without pomalidomide, in patients who have received earlier lines of therapy, including a proteasome inhibitor and lenalidomide, which is currently being investigated in the registrational, Phase 3 MonumenTAL-3 study.1
"We continue to be encouraged by the potential versatility of TALVEY as a combination partner with other therapies to address unmet needs for patients with relapsed or refractory multiple myeloma who have limited treatment options at this advanced stage," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Innovative Medicine at Johnson & Johnson. "By simultaneously targeting GPRC5D and CD38 on myeloma cells with the combination of TALVEY and DARZALEX FASPRO, we are aiming to attack multiple myeloma in different ways to help improve outcomes for patients with this serious illness and limited treatment options."
Additional data underscoring the combinability of TALVEY® from the RedirecTT-1 study will also be presented at IMS. Results from the TRIMM-2 study were previously presented at the 2023 ASCO Annual Meeting.
About TRIMM-2 Study
The TRIMM-2 (NCT04108195) study is an ongoing Phase 2 study of DARZALEX FASPRO® regimens in combination with TALVEY® for the treatment of patients with multiple myeloma. The primary objectives of the TRIMM-2 study were to identify the Phase 2 dose (RP2D) for each component of the treatment combination (Part One); characterize the safety of the treatment combination at the RP2D (Part 2); and assess antitumor activity, pharmacokinetics and pharmacodynamics for the combination treatment (Part 3). Patients in the study (N=65) all had multiple myeloma and had received a minimum three prior lines of therapy or were double refractory to a proteasome inhibitor (PI) and an immunomodulatory agent; patients who had been exposed or refractory to an anti-CD38 therapy more than ninety days prior to the start of the trial were also included, as well as those refractory to anti-CD38 therapy.
About MonumenTAL-3
The MonumenTAL-3 (NCT05455320) study is an ongoing Phase 3 study of TALVEY® in combination with DARZALEX FASPRO® with or without pomalidomide compared to DARZALEX FASPRO® combined with pomalidomide and dexamethasone in patients with relapsed of refractory multiple myeloma who have received at least one prior line of therapy.
About Multiple Myeloma
Multiple myeloma is a blood cancer affecting a type of white blood cell called plasma cells found in the bone marrow.2 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.3 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.4 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.5 People with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.7, 8
