Safety and efficacy of talquetamab + teclistamab in patients with Relapsed/Refractory multiple myeloma from Phase 1b of redirectt-1: Results with an extended median follow-up of 3 years
Abstract
Abstract Introduction: Talquetamab (Tal, anti-GPRC5D×CD3) and teclistamab (Tec, anti-BCMA×CD3) are the first bispecific antibodies (BsAbs) approved as monotherapies for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). In previous results from the phase 1b portion of RedirecTT-1 (NCT04586426, March 2024 data cut; median follow-up [mFU] 20.3 mo), Tal + Tec elicited deep, durable responses and demonstrated a safety profile generally consistent with each monotherapy across all dose levels (DLs), including at the recommended phase 2 regimen (RP2R) of Tal 0.8 mg/kg + Tec 3.0 mg/kg Q2W and in patients (pts) with true extramedullary disease (EMD). We report efficacy and ongoing safety from phase 1b of RedirecTT-1 at an extended mFU of 36.2 mo. Methods: Pts had TCE RRMM with measurable disease per IMWG criteria and were refractory, relapsed, or intolerant to the last line of therapy. True EMD was defined as ≥1 nonradiated soft tissue plasmacytoma noncontiguous with bone ≥2 cm in 1 dimension (with or without paramedullary plasmacytomas). Primary objectives were to evaluate safety and identify a RP2R. Investigator-assessed confirmed response per IMWG criteria was reported in all treated pts. EMD response was assessed by CT, PET-CT, or MRI whole-body scans. Results: As of July 2025, 94 pts received Tal + Tec (44 pts at the RP2R), with a mFU of 36.2 mo (34.1 mo at the RP2R). Baseline characteristics were as previously reported; 23 (45.1%) pts had high-risk cytogenetics. Dose-limiting toxicities occurred in 3 pts across non-RP2R DLs (all grade [gr] 3; oral herpes, oral candidiasis, increased alanine/aspartate aminotransferase) and in 1 pt at the RP2R (gr 4 thrombocytopenia). Most common adverse events (AEs) were CRS (80.9%; gr 3, 2.1%; no gr 4/5), neutropenia (74.5%; gr 3/4, 70.2%), taste changes (66.0%; all gr 1/2), and non-rash skin AEs (62.8%; gr 3, 2.1%). Infections occurred in 93.6% of pts (gr 3/4, 68.1% [54.5% at the RP2R]). The most common infection was COVID-19 (40.4%; gr 3/4, 17.0%); pts were screened for enrolment between 2020–2023, concurrent with the COVID-19 pandemic. Opportunistic infections occurred in 16 (17.0%) pts. Eighty-four (89.4%) pts had posttreatment hypogammaglobulinemia; 61 (64.9%) pts received ≥1 dose of IgG. ICANS occurred in 3.2% of pts (gr 3/4, 1.1%). Overall, 18 (19.4%) pts discontinued Tal + Tec due to AEs (6 [14.0%] at the RP2R), of which 9 were deemed drug-related by investigator (2 at the RP2R); 12 discontinuations were due to infections (5 at the RP2R). One pt discontinued Tal only. In total, 18 (19.1%) pts died due to AEs (6 [13.6%] at the RP2R), of which 9 (9.6%) were deemed drug-related by investigator (2 [4.5%] at the RP2R). At the RP2R, overall response rate (ORR) was 79.5%, with a ≥CR rate of 61.4%; ORR was 61.1% (≥CR, 44.4%) in pts with EMD and 92.3% (≥CR, 73.1%) in pts without EMD. Across all DLs, ORR was 77.7% (≥CR, 52.1%). Responses continued to be durable at the RP2R and across all DLs, including in pts with EMD, consistent with previous results. The median duration of response (DOR) was non-estimable (NE) at the RP2R (NE with and without EMD), as well as across all DLs, with 36-mo DOR rates of 71.1% at the RP2R (61.4% with EMD, 76.4% without EMD) and 58.5% across all DLs. Progression-free survival (PFS) and overall survival (OS) were promising at an extended mFU. Median PFS was NE at the RP2R (21.6 mo with EMD, NE without EMD) and 38.6 mo across all DLs, with 36-mo PFS rates of 57.9% at the RP2R (39.7% with EMD, 70.5% without EMD) and 52.6% across all DLs. Median OS was NE at the RP2R (NE with and without EMD), as well as across all DLs, with 36-mo OS rates of 73.9% at the RP2R (57.0% with EMD, 83.2% without EMD) and 65.8% across all DLs. Conclusions: At an extended mFU of ~3 yrs, Tal + Tec continued to have a safety profile that was generally consistent with each monotherapy, with no exacerbation of AEs with the combination. The infection profile supported prophylaxis and vigilant monitoring and management. Tal + Tec led to a high ORR and deep, durable responses in all pts, including at the RP2R and in pts with true EMD, contributing to durable PFS observed across all pts. DOR and prolonged survival in pts with and without EMD exceeded all therapies for pts with TCE RRMM. These data continue to highlight the clinical benefit of the novel combination of Tal + Tec in pts with TCE RRMM, validating the RP2R and the ongoing phase 2 analyses in pts with true EMD.
Article Details
Authors (26)
María-Victoria Mateos
Hila Magen
Chaim Sheba Medical Center, Ramat-Gan, Israel
Moshe Gatt
Hadassah Medical Cener, Hebrew University of Jerusalem, Jerusalem, Israel
Michael Sebag
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Kihyun Kim
Division of Hematology–Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
Chang-Ki Min
Seoul St. Mary’s Hospital, Catholic University of Korea, Seoul, South Korea
Enrique Ocio
1HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA, Hematology, Santander, Spain
Sung-Soo Yoon
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Michael Chu
1University of Alberta, Hematology, Edmonton, Canada
Paula Rodriguez-Otero
Irit Avivi
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Natalia Quijano Carde
12Johnson & Johnson, Spring House, United States
Maria Krevvata
Johnson & Johnson, Spring House, PA
Todd Henninger
Johnson & Johnson, Raritan, NJ
Payal Thakkar
Johnson & Johnson, Raritan, NJ
Mariacristina Festa
Johnson & Johnson, Leiden, the Netherlands
Lin Huang
Jiangxiu Zhou
Johnson & Johnson, Spring House, PA
Mikihiro Takamoto
Johnson & Johnson, Tokyo
Lixia Pei
Johnson & Johnson, Raritan, NJ
Jiashen Lu
Johnson & Johnson, Shanghai
Carmela Maffucci
13Johnson & Johnson, Raritan, United States
Emma Scott
Johnson & Johnson, Spring House, PA
Albert Oriol
Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain
Daniel Morillo
From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) — all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) — all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary’s Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) — all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d’Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.)...
Yaël Cohen
7Tel Aviv University, Tel Aviv Sourasky Medical Center & Faculty of Medical and Health Sciences, Tel Aviv, Israel