DREAMM-9: Phase I Study of Belantamab Mafodotin Plus Standard of Care in Patients with Transplant-Ineligible Newly Diagnosed Multiple Myeloma

ABSTRACT

Introduction: The bortezomib, lenalidomide, and dexamethasone (VRd) regimen is an acceptable standard of care (SoC) for both transplant-eligible and transplant-ineligible newly diagnosed multiple myeloma (TI NDMM). Ongoing development of novel therapies and combinations strive to improve survival outcomes beyond what is expected from SoC. Belantamab mafodotin (belamaf) is a B-cell maturation antigen-binding antibody-drug conjugate that eliminates myeloma cells by a multimodal mechanism and has demonstrated durable responses in patients with relapsed/refractory multiple myeloma (RRMM). Preclinical evidence of belamaf in combination with bortezomib or lenalidomide suggests enhanced anti-myeloma activity, providing rationale for this treatment combination. We report the preliminary findings of belamaf + VRd for TI NDMM patients. Methods: DREAMM-9 (NCT04091126) is an ongoing Phase I, open-label, randomized, dose and schedule evaluation study of belamaf + VRd in patients with TI NDMM. Eligible patients include those ≥18 years old with ECOG status 0-2 and adequate organ system functions. The study evaluates safety and tolerability of belamaf + VRd in up to 8 cohorts, up to 144 patients, to establish the recommended phase 3 dose (RP3D). VRd is administered Q3W until cycle 8, followed by lenalidomide + dexamethasone (Rd) Q4W. Belamaf + VRd is administered until cycle 8, and then in combination with Rd thereafter. The belamaf dose cohorts currently being evaluated are cohort 1 (1.9 mg/kg Q3/4W), cohort 2 (1.4 mg/kg Q6/8W), cohort 3 (1.9 mg/kg Q6/8W), cohort 4 (1.0 mg/kg Q3/4W), and cohort 5 (1.4 mg/kg Q3/4W). After evaluation of safety data for cohort 1, cohorts 2-5 were opened in parallel and enrolled patients were randomized 1111. Safety data, clinical activity, and drug concentrations will be assessed, and used to determine the belamaf RP3D. This analysis reports the preliminary results from cohort 1. Primary endpoints include number of patients with adverse events (AEs). Secondary endpoints include establishing relative dose intensity of lenalidomide and bortezomib in combination with belamaf, cumulative dose of belamaf, pharmacokinetics (PK) profile of belamaf when combined with VRd, overall response rate (ORR), complete response (CR), stringent complete response (sCR), complete response rate ([CRR];% of patients with a confirmed CR or better), and rate of very good partial response or better (≥VGPR). Exploratory endpoints include assessing minimal residual disease (MRD) in patients who achieve ≥VGPR, and safety and efficacy exposure-response relationships. Results: Twelve patients in cohort 1 were included in this preliminary analysis. Eight patients (67%) were male;median age (range) was 72.5 years (63-77). Ten patients (83%) were white and 2 (17%) were Asian. Nine patients (75%), were ISS stage II or III, and 4 (33%) patients had high-risk cytogenetics (consisting of one or more of the following t(4;14), t(14;16), del17p, 17p13del). AEs related to study treatment were experienced by all 12 patients. Dose reductions occurred in 12 (100%) patients, all of whom also experienced a dose delay. Most common AEs leading to dose modification were thrombocytopenia, neutropenia, and corneal events. Grade 3 or 4 AEs related to belamaf occurred in 9 (75%) patients. During the trial, one patient experienced a fatal severe AE due to COVID-19 infection (unrelated to study treatment;Table). All patients, 100% (n=12;95% CI 73.5-100) achieved ≥VGPR. Early deep responses were observed;2 (17%) patients achieved VGPR as early as 4 weeks. As of data cut-off, 5 (42%) remain in CR and 3 (25%) in sCR. Based on real-time data captured in the clinical database, 7 out of 9 patients achieved MRD-negative status at the first test after VGPR. Belamaf PK profile was similar to that observed in patients with RRMM taking into consideration baseline patients characteristics. Conclusion: Preliminary data suggest addition of belamaf to VRd did not reveal new safety signals and demonstrates high response rates, albeit with short follow up. The study is ongoing to confirm safety and evaluate the efficacy of belamaf + VRd. Updated data for cohort 1 will be reported at the congress. Funding: GSK (Study 209664);belamaf drug linker technology licensed from Seagen;belamaf monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. [Formula presented] Disclosures Usmani Pharmacyclics Consultancy, Research Funding;Seattle Genetics Consultancy, Research Funding;Takeda Consultancy, Research Funding, Speakers Bureau;Merck Consultancy, Research Funding;SkylineDX Consultancy, Research Funding;Sanofi Consultancy, Research Funding, Speakers Bureau;Janssen Consultancy, Research Funding, Speakers Bureau;Janssen Oncology Consultancy, Research Funding;Bristol-Myers Squibb Research Funding;EdoPharma Consultancy;GSK Consultancy, Research Funding;Celgene/BMS Consultancy, Research Funding, Speakers Bureau;Array BioPharma Consultancy, Research Funding;Abbvie Consultancy;Amgen Consultancy, Research Funding, Speakers Bureau. Quach Celgene Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Karyopharm Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;GlaxoSmithKline Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Janssen/Cilag Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Sanofi Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Bristol Myers Squibb Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene Consultancy, Membership on an entity's Board of Directors or advisory committees;Takeda Consultancy, Membership on an entity's Board of Directors or advisory committees;CSL Consultancy, Membership on an entity's Board of Directors or advisory committees. Koh Pfizer Consultancy;Jassen Honoraria;AstraZeneca Honoraria;Novartis Honoraria;GSK Honoraria;Roche Honoraria;Takeda Honoraria. Guenther Novartis Consultancy;Celgene Consultancy, Honoraria;Roche Consultancy;Takeda Consultancy, Honoraria;Amgen Consultancy, Honoraria;AbbVie Consultancy;Jazz Pharmaceuticals Honoraria;Janssen Pharmaceuticals Consultancy, Honoraria. Zhou GlaxoSmithKline Current Employment. Kaisermann GlaxoSmithKline Current Employment, Current equity holder in publicly-traded company. Mis GlaxoSmithKline Current Employment. Williams GlaxoSmithKline Current Employment. Yeakey GlaxoSmithKline Current Employment, Current equity holder in publicly-traded company. Ferron-Brady GlaxoSmithKline Current Employment, Current equity holder in publicly-traded company. Figueroa GlaxoSmithKline Current Employment. Kremer GlaxoSmithKline Current Employment. Gupta Novartis Current equity holder in publicly-traded company;GlaxoSmithKline Current Employment, Current equity holder in publicly-traded company. Janowski Celgene Consultancy;AstraZeneca Consultancy, Membership on an entity's Board of Directors or advisory committees;Janssen Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS Membership on an entity's Board of Directors or advisory committees.