• As of Feb 4, 2021, 156 pts received teclistamab (IV n = 84; SC n = 72). The RP2D, identified as weekly SC 1500 µg/kg teclistamab with 60.0 and 300 µg/kg step-up doses, was given to 40 pts (median follow-up 4.3 mo [range 1.1–10.4+]).
• Patients dosed at the RP2D (median age, 62.5 y [range, 39–84]; 65% male) had received a median of 5 prior lines of therapy (range 2–11; 100% triple-class exposed; 65% penta-drug exposed; 83% triple-class refractory; 35% penta-drug refractory; 85% refractory to their last line of therapy).
• There were no dose-limiting toxicities at the RP2D in part 1. The most common AEs at the RP2D were CRS (70%; grade 3/4 0) and neutropenia (60%; grade 3/4 40%); grade 1 neurotoxicity was reported in 1 (3%) patient.
• Median time to CRS onset was later with SC vs IV dosing (day after SC injection vs day of IV infusion).
• The overall response rate in response-evaluable patients treated at the RP2D (n = 40) was 65%;
  • 58% achieved a very good partial response or better and 30% achieved a complete response (CR) or better;
  • median time to first confirmed response was 1.0 mo (range 0.2–3.1).
• At the RP2D, median duration of response was not reached; 23 of 26 responders (88%), after median follow-up of 5.3 mo (range 1.2–10.4+), were alive and continuing on treatment with responses deepening over time.
• Of 14 evaluable pts across all cohorts, 9 with CR were minimal residual disease–negative at 10^-6. At the RP2D, teclistamab exposure was sustained across the dosing interval and exceeded target levels, and consistent T cell activation was observed.

As of 20 Jul 2020, iv teclistamab (0.3–720 µg/kg) and sc teclistamab (80–3000 µg/kg) were received by 84 and 44 pts, respectively. Overall, median age was 64 y (24–82), median number of prior lines of therapies (LOT) was 6 (2–14), 95%/79% triple-class exposed/refractory, 70%/38% penta-drug exposed/refractory, and 91% refractory to last LOT. AEs in >20% of pts (both iv and sc combined) included anemia (55%), neutropenia (55%), thrombocytopenia (41%), and leukopenia (26%), as well as non-hematologic events of CRS (53%), pyrexia (28%), diarrhea (24%), cough (23%), fatigue (23%), nausea (22%), back pain (20%), and headache (20%). 39% of pts had treatment-related grade ≥3 AEs; neutropenia (23%) and anemia (9%) were most frequent. CRS occurred in 55% and 50% of pts with iv and sc dosing, respectively, tending to occur later (relative to the most recent dose) with sc administration (median time to onset of 1.0 day iv and 2.0 days sc). CRS events were all gr 1 (n=51) or 2 (n=17) and generally confined to initial doses. 5% of pts (all iv) had neurotoxicity (2% gr ≥3), and 12% had treatment-related infusion/injection related reaction (including 4 infusion reactions [all iv, 5%] and 11 injection related reactions [all sc, 25%], all gr 1/2). Gr 3 or higher infection-related AEs were reported in 15% of pts (3% treatment related). Four gr 5 AEs were reported (all iv and considered unrelated to treatment by investigator except for 1 case of pneumonia).

120 pts were evaluable for response, with the highest and most active dose levels of 270 µg/kg and 720 µg/kg weekly for iv and 720 µg/kg and 1500 µg/kg weekly for sc (of note, response data for 3000 µg/kg sc is not yet mature). Combining these 4 iv and sc dose levels, ORR was 30/47 (63.8%, including n=24 with very good partial response [VGPR] or better and n=9 with complete response [CR] or better). 1500 µg/kg sc was selected as a RP2D, and currently at this dose, 6 of 6 pts are in response (3 PR, 1 VGPR, 2 stringent CR) with progressive deepening of responses over time.

• The study involved 78 patients with relapsed/refractory myeloma who received teclistamab — a bispecific duo antibody that binds to BCMA and CD3 – intravenously.
• Median age was 64 years old (range, 24-82), and the median number of prior therapies was 6 (range, 2-14).
• Overall, 72% of participants were triple-class exposed, 62% triple-class refractory, and 51% penta-drug refractory.
• Part 1 of the study was a dose-escalation trial, with a primary objective of finding the doses for part 2. Doses ranged from 0.3-720 µg/kg weekly, and there was a 67% overall response rate (ORR; 50% ≥ VGPR) at 270 µg/kg.
• "Response rates increased with higher doses of teclistamab," Dr. Usmani said.