Details

Autor(en) / Beteiligte

• Usmani, Saad Zafar
• Mateos, Maria-Victoria
• Nahi, Hareth
• Krishnan, Amrita Y.
• van de Donk, Niels W.C.J.
• San Miguel, Jesus
• Oriol, Albert
• Rosiñol, Laura
• Chari, Ajai
• Adams, Homer
• Girgis, Suzette
• Wang Lin, Shun Xin
• Stephenson, Tara
• Kemmerer, Kristy
• Smit, Jennifer
• Elsayed, Yusri A.
• Infante, Jeffrey R.
• Goldberg, Jenna D.
• Banerjee, Arnob
• Garfall, Alfred L.

Titel

Phase I study of teclistamab, a humanized B-cell maturation antigen (BCMA) x CD3 bispecific antibody, in relapsed/refractory multiple myeloma (R/R MM)

Ist Teil von

• JOURNAL OF CLINICAL ONCOLOGY, 2020, Vol.38 (15_suppl), p.100-100

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Abstract only 100 Background: Teclistamab (JNJ-64007957) is a bispecific BCMA x CD3 antibody that induces T cell-mediated cytotoxicity against BCMA-expressing myeloma cells. Initial results from an ongoing study of teclistamab in RRMM (NCT03145181) are presented. Methods: Pts have MM and are RR to standard therapies. Primary objective for part 1 is to identify a recommended phase 2 dose(s). Multiple intravenous (iv) doses ± priming doses were explored. Adverse events (AEs) were graded per CTCAE v4.03 and cytokine release syndrome (CRS) per Lee et al 2014. Response was investigator-assessed using IMWG criteria; minimal residual disease (MRD) in bone marrow was assessed by next generation sequencing. Results: As of 31 Jan 2020, 66 pts had received iv teclistamab (0.3–270 µg/kg). Median age was 64 y (24–82), median prior therapies was 6 (2–14), 97% triple-class exposed, 83% triple-class refractory, and 38% penta-drug refractory. Most common treatment-related AEs (all grade) were CRS (56%), neutropenia (26%), and anemia (23%). CRS events were all grade 1–2 and generally confined to initial doses. 8% of pts had treatment-related neurotoxicity (3% grade ≥3), and 9% had infusion related reaction. Infection-related AEs were reported in 61% of pts (21% grade ≥3). 2 dose-limiting toxicities were reported: grade 4 delirium (resolved after 16 days) and grade 4 thrombocytopenia (resolved after 1 day). 36% of pts had treatment-related grade ≥3 AEs; neutropenia (20%) and anemia (14%) were most frequent. Only 1 grade 5 AE was reported (respiratory failure in the setting of pneumonia deemed unrelated by the investigator). PK results indicate that the half-life of teclistamab supports weekly dosing. On-target pharmacodynamic activity (T cell redistribution and activation along with transient release of cytokines) was observed at doses ≥9.6 µg/kg. Cytokine production was modulated with step-up dosing while T cell activation was maintained. 65 pts were evaluable for response. Activity was observed starting at treatment doses ≥38.4 µg/kg, with 20/52 (38%) pts achieving a response. At the highest dose, 7/9 (78%) pts responded (1 response pending confirmation). Of MRD-evaluable pts who had complete response, 2/2 were MRD negative at 10 −6 with treatment ongoing > 12 mo. Conclusions: Teclistamab has manageable safety across all doses explored. A 78% overall response rate was observed at the highest weekly treatment dose in pts with advanced RRMM, supporting further evaluation of teclistamab in expansion cohorts. Clinical trial information: NCT03145181.