Updated follow‐up of BELLWAVE‐001: an open‐label, single‐arm, phase 1/2 study of the efficacy and safety of nemtabrutinib for the treatment of B‐cell malignancies

Background: Bruton tyrosine kinase inhibitors (BTKis) are standard of care for chronic lymphocytic leukemia/small lymphoma (CLL/SLL), but resistance can develop, most commonly because BTK mutations. Nemtabrutinib inhibits both wild-type and C481S-mutant BTK. Initial results from the phase 1/2 BELLWAVE-001 study (NCT03162536) showed that recommended 2 dose (RP2D) nemtabrutinib (65 mg QD) had a manageable safety profile promising antitumor activity in heavily pretreated patients (pts) with relapsed or refractory (R/R) CLL/SLL, including pts whose disease progressed after prior covalent BTKis. We present updated analyses on efficacy RP2D hematologic malignancies. Methods: Pts CLL/SLL were enrolled cohort A (R/R ≥2 therapies, BTKi, C481-mutated BTK) B intolerant to without B-cell non-Hodgkin cohorts C-I. received 65 QD until unacceptable toxicity, progression, other discontinuation criteria met. Primary end points ORR (for pts, per 2018 iwCLL by investigator), RP2D. Secondary DOR safety. Efficacy included all who ≥1 nemtabrutinib. Results: 112 treated mg; 57 CLL/SLL. Among median age was 66 years (range, 45–86), 16 (28%) female, 51 (89%) ECOG PS ≤1. number lines therapy 4 2–18), BTKi therapy, 27 (47%) BCL2i 36 (63%) C481S-mutated At data cutoff (October 28, 2022), follow-up 9.4 months 0.1–45.5). mg, 32 an objective response (ORR, 56% [95% CI, 42–69]; CR; 15 PR; PR residual lymphocytosis [PR-L]); 26.0 (95% 13.9-not reached [NR]). (n = 25) 10) 35–76; 10 PR-L) 40% 12–74; 1 PR-L), respectively; 16.6 5.7–26.0) NR, respectively. hematological malignancies 82 (73%) any-grade treatment-related AEs, common (≥15%) dysgeusia (21%) decreased neutrophil count (20%). Grade 3 AEs occurred 47 (42%); (≥5%) (17%) platelet (7%). No deaths attributed treatment. Conclusion: With ∼9 follow-up, continued show R/R The research funded by: Merck Sharp & Dohme LLC, subsidiary Co., Inc., Rahway, NJ, USA Keywords: Aggressive lymphoma, Chronic Lymphocytic Leukemia (CLL), Molecular Targeted Therapies Conflicts interests pertinent abstract. H. Eradat Consultant advisory role: Abbvie, Genentech, Morphosys, Incyte, Beigene Honoraria: Beigene, Pharmacyclics Research funding: ATARA, Juno, BMS, Celgene, Pharmacyclics, AstaZeneca, Kite, Gilead Other remuneration: Speaker bureau: J. Woyach AbbVie, ArQule, AstraZeneca, BeiGene, Janssen, MorphoSys, Newave, Karyopharm, Loxo Oncology, Schrodinger I. W. Flinn Consultancy: All payments made Sarah Cannon Institute, not physician. Century Therapeutics, Genmab, Hutchison MediPharma, Iksuda InnoCare Pharma, Kite Myeloid Novartis, Nurix Roche, Secura Bio, Servier Pharmaceuticals, Takeda, TG Verastem, Vincerx Xencor Grants: Acerta Agios, Biopath, Bristol Myers Squibb, CALIBR, CALGB, City Hope National Medical Center, Constellation Curis, CTI Biopharma, Epizyme, Fate Forma Forty Seven, Sciences, IGM Biosciences, Infinity Loxo, Merck, Millennium Nurix, Pfizer, Portola Rhizen Seattle Genetics, Tessa TCR2 Trillium Triphase Development Corp., Unum seventy bio F. T. Awan Astrazeneca, sciences, pharma, MEI Johnson Johnson, Dava Cardinal Health, ADCT therapeutics, Caribou Cellecter Bisosciences D. Brander ArQule/Merck, Therapeutics ArQule,/Merck, Ascentage, Astra Zeneca/Acerta, CATO/SMS Catapult, DTRM, Juno/Celgene/Bms, NeWave, Therapeutics-Grants paid institution S. A. Parikh GlaxoSmithKline, Adaptive Biotechnologies, Amgen, AbbVie Ascentage Pharma Phillips ADC Therapuetics, Bayer, Eli Lily, Gilead, Genentech R. Ghori Employment leadership position: Inc. Stock ownership: Paydar M. Z. Farooqui C. Byrd Abbvie; Zeneca; Kura, Syndax, Trillium, Zencor; Patents/Royalties: OSU Stephens Lilly, CSL Behring, Celgene Acerta, Mingsight, Arqule, JUNO, Newave