BACKGROUND

ELRA is a humanized, BCMA/CD3 bispecific antibody. In the phase 2 registrational MagnetisMM-3 (MM-3) trial, SC ELRA given as 2 step-up priming doses (12 mg on day 1 and 32 mg on day 4 of cycle 1) followed by 76 mg QW in patients (pts) with RRMM naive to BCMA-directed therapy resulted in an ORR of 61.0%. With a median follow-up of 28.4 mos, the median DOR, PFS, and OS were not reached (NR; 2-year rate, 66.9%), 17.2, and 24.6 mos, respectively. Overall, 56.3% of pts had CRS (grade 2, 14.3%; no grade ≥3). Most events occurred after doses 1 (44.5%), 2 (20.2%), and 3 (5.9%); 0.8% (1 pt) had CRS with doses ≥4. Recurrent CRS occurred in 15.1% of pts. The phase 1/2 MagnetisMM-9 (MM-9; NCT05014412) study is examining an alternative priming regimen and longer dosing intervals of ELRA. Here, we present updated MM-9 results.

METHODS

In MM-9, pts with RRMM and disease refractory to ≥1 IMiD drug, ≥1 PI, and ≥1 anti-CD38 antibody were given SC ELRA as step-up priming doses of 4 and 20 mg on Day 1 and Day 4 of Cycle 1, respectively. After the priming doses, ELRA 76 mg was given QW for the next 6 cycles (Part 1) or for 1 cycle followed by 116 (dose level 1 [DL1]) or 152 (dose level 2 [DL2]) mg Q2W for the next 5 cycles (Part 2A). After 6 cycles, the dosing frequency was decreased from QW to Q2W (Part 1) or from Q2W to Q4W (Part 2) in pts who achieved ≥PR lasting ≥2 months. The recommended phase 2 dose from Part 2A (152 mg, DL2) was evaluated in Part 2B (dose expansion). The primary endpoint for both parts is grade ≥2 CRS rate per ASTCT criteria during Cycle 1. Secondary endpoints include evaluation of efficacy and adverse events. Data cutoff: February 13, 2024.

RESULTS

Overall, 85 pts (median age, 64.0 y) were treated with ELRA. The majority (72.9%) of pts had R-ISS stage I/II disease (23.5% with R-ISS stage III); 31.8% had high-risk cytogenetics. Median number of prior lines of therapy was 5.0 (range, 1-12).

The median treatment duration was 8.6, 2.9, 1.4, and 3.3 mos, in Part 1, Part 2A DL1, Part 2A DL2, and Part 2B, respectively. Median follow-up for pts overall (n=85), in Part 1 (n=33), Part 2A DL1 (n=12), Part 2A DL2 (n=11), and Part 2B (n=29) was 10.4, 23.3, 16.5, 15.2, and 9.3 mos, respectively. Overall, the ORR was 58.8%. For pts in Part 1, Part 2A DL1, Part 2A DL2, or Part 2B, ORR was 66.7%, 58.3%, 36.4%, and 58.6%, respectively; median DOR was NR (9-mo rate: 86.4%), 10.8 mos (9-mo rate: 80.0%), NR (9-mo rate: 100.0%), and NR (9-mo rate: 84.8%); median PFS was 17.1 (9-mo rate: 62.8%), 11.6 (9-mo rate: 50.9%), 1.6 mos (9-mo rate: 40.0%), and NR (9-mo rate: 57.1%); median OS was NR (9-mo rate: 75.8%), 17.4 mos (9-mo rate: 66.7%), NR (9-mo rate: 60.0%), and NR (9-mo rate: 72.4%), respectively.

For pts in Part 1, Part 2A DL1, Part 2A DL2, and Part 2B, grade ≥2 CRS rates during Cycle 1 were 15.2%, 16.7%, 27.3%, and 6.9%, respectively. For pts in Part 1, Part 2A DL1, Part 2A DL2, and Part 2B, CRS rates were 30.3%, 33.3%, 36.4%, and 24.1% after dose 1, 27.3%, 25.0%, 36.4%, and 24.1% after dose 2, 15.2%, 33.3%, 27.3%, and 20.7% after dose 3, 6.1%, 8.3%, 0%, and 3.4% after dose 4, and 6.1%, 16.7%, 9.1%, and 0% after doses ≥5. Recurrent CRS occurred in 18.2%, 33.3%, 18.2%, and 17.2% of pts in Part 1, Part 2A DL1, Part 2A DL2, and Part 2B.

The most common (>60%) TEAEs (any grade/grade ≥3) were hematologic TEAEs (Part 1, 75.8%/75.8%; Part 2A DL1, 83.3%/83.3%; Part 2A DL2, 81.8%/81.8%; Part 2B, 79.3%/69.0%), infections (Part 1, 78.8%/48.5%; Part 2A DL1, 83.3%/66.7%; Part 2A DL2, 72.7%/63.6%; Part 2B, 62.1%/37.9%), and CRS (Part 1, 60.6%/0%; Part 2A DL1, 83.3%/0%; Part 2A DL2, 90.9%/9.1%; Part 2B, 48.3%/0%). Grade 5 TEAEs not including PD were infection (n=4), fall (n=1), subdural hematoma (n=1), and food poisoning (n=1).

CONCLUSIONS

The 4/20 mg step-up priming regimen and alternative dosing schedules in MM-9 resulted in similar efficacy vs the step-up regimen used in the registrational MM-3 study (12/32 mg). Responses were durable with encouraging PFS and OS with the alternative step up and longer dosing schedule. While the overall safety signals with the alternative step up regimen are similar to those seen with MM-3, the CRS profile differed with more CRS events after each subsequent dose and a higher prevalence of recurrent CRS. Thus, the optimal ELRA step-up regimen remains 12/32 mg from the original regimen in the MM-3 study. In addition, these early results suggest that reducing the dose frequency of ELRA may not compromise efficacy.

Disclosures

Pianko:AbbVie, Ascentage, Bristol Myers Squibb, Janssen, Nektar, Pfizer, Regeneron, Sanofi: Research Funding; Janssen, Karyopharm, Oncopeptides, Pfizer, Sanofi: Honoraria; Janssen, Pfizer: Consultancy. Pawlyn:GSK: Honoraria; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; iTEOS Therapeutics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Menarini Stemline: Honoraria; Abbvie: Honoraria. Sborov:Society of Utah Medical Oncology: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Parexel, Keosys: Other: IRC; University of Utah, Huntsman Cancer Institute: Current Employment; AstraZeneca: Consultancy; Genentech, Inc.: Consultancy; Arcellx: Consultancy; Sanofi: Consultancy; Abbvie: Consultancy; GlaxoSmithKline: Consultancy; Bristol Myers Squibb: Consultancy; Legend Biotech: Consultancy; Janssen: Consultancy; Bioline: Consultancy; Binaytara Foundation: Honoraria. Iida:Pfizer: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; GlaxoSmithKlein: Consultancy, Research Funding; Otsuka: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Shionogi: Research Funding; Alexion: Research Funding; Chugai: Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. Ramakrishnan:Novartis: Research Funding; BMS: Research Funding; Gracell/AstraZeneca: Research Funding; Janssen: Research Funding; Poseida: Research Funding; Pfizer: Research Funding; Kite: Research Funding; Marker: Research Funding; Cellectis: Honoraria; Juno: Research Funding; Autolus: Research Funding; Sumitomo: Research Funding; Schrodinger: Research Funding; Macrogenics: Research Funding; Fate: Research Funding; Chimeric: Research Funding; Sanofi: Research Funding; Kadmon: Research Funding. Benjamin:Alimera Sciences; Servier: Research Funding; Allogene Therapeutics, Arovella Therapeutics, Bristol-Myers Squibb, Janssen, Oncopeptides, Secura Bio: Consultancy. Popat:Regeneron: Other: IDMC member; BMS: Honoraria; GSK: Honoraria, Research Funding; Roche: Honoraria; Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Abbvie: Honoraria; J&J: Honoraria. Kuroda:Kyowa Kirin, Chugai Pharmaceutical, Japan Blood Product Organization, Sumitomo Pharmaceutical, Otsuka Pharmaceutical, Asahikasei, Taiho Pharmaceutical, Mochida Pharmaceutical: Research Funding; Janssen Pharmaceutical, AbbVie, Pfizer, BeiGene, Bristol Myers Squibb: Consultancy; Janssen Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Sanofi, Bristol Myers Squibb, Novartis, AbbVie, Pfizer, Astellas Pharmaceutical, Nippon Shinyaku, Genmab, Pharma Essentia Japan: Honoraria; Bristol Myers Squibb, Pfizer, Janssen Pharmaceutical: Membership on an entity's Board of Directors or advisory committees. Philippe:Pfizer, Inc, Paris, France: Current Employment, Current equity holder in private company. Conte:Takeda, Janssen, Pfizer, and BMS: Research Funding; Pfizer: Current holder of stock options in a privately-held company; Alexion, Bristol Myers Squibb, Janssen, Pfizer, and Takeda: Other: Other intellectual property, grants and contracts, Patents & Royalties; Ono, Takeda, BMS, Janssen, and Sanofi: Honoraria; Pfizer: Current Employment, Current holder of stock options in a privately-held company. Hong:Pfizer, Inc. Cambridge, MA: Current Employment, Current holder of stock options in a privately-held company. Vandendries:Pfizer: Current Employment, Current equity holder in private company. Fonseca:Patent for FISH in MM - ~$2000/year: Patents & Royalties: Patent for FISH in MM - ~$2000/year; Celgene, Bristol Myers Squibb, Bayer, Amgen, Janssen, Kite, a Gilead company, Merck Sharp & Dohme, Juno Therapeutics, Takeda, AbbVie, Aduro Biotech, Sanofi, OncoTracker: Honoraria; Antengene: Membership on an entity's Board of Directors or advisory committees; AbbVie, Adaptive, Amgen, Apple, Bayer, BMS/Celgene, Gilead, GSK, Janssen, Kite, Karyopharm, Merck Sharp & Dohme, Juno Therapeutics, Takeda, Arduro Biotech, Oncotracker, Oncopeptides, Pharmacyclics, Pfizer, RA Capital, Regeneron, Sanofi: Consultancy.

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2024
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