Bortezomib, lenalidomide, and dexamethasone (VRd) ± daratumumab (DARA) in patients (pts) with newly diagnosed multiple myeloma (NDMM) for whom transplant is not planned as initial therapy: A multicenter, randomized, phase III study (CEPHEUS).

person Sonja Zweegman Department of Hematology, Amsterdam UMC, Amsterdam, Netherlands info_outline Sonja Zweegman, Saad Zafar Usmani, Katherine Chastain, Jodi Carey, Karen Ren, Elena Smith, Maria Krevvata, Jianping Wang, Jessica Vermeulen, Thierry Facon

Authors person Sonja Zweegman Department of Hematology, Amsterdam UMC, Amsterdam, Netherlands info_outline Sonja Zweegman, Saad Zafar Usmani, Katherine Chastain, Jodi Carey, Karen Ren, Elena Smith, Maria Krevvata, Jianping Wang, Jessica Vermeulen, Thierry Facon Organizations Department of Hematology, Amsterdam UMC, Amsterdam, Netherlands, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Atrium Health, Charlotte, NC, Janssen Research & Development, Raritan, NJ, Janssen Research & Development, Spring House, PA, Janssen Research & Development, LLC, High Wycombe, United Kingdom, Janssen Research & Development, LLC, Leiden, Netherlands, Service des Maladies du Sang, Hôpital Claude Huriez, Lille, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: DARA is a human, anti-CD38 IgGκ monoclonal antibody that significantly reduced the risk of progression/death with a manageable safety profile across several phase 3 studies in relapsed/refractory MM and NDMM. DARA + VRd (D-VRd) demonstrated efficacy and tolerability in the safety run-in cohort of the ongoing phase 2 GRIFFIN study that included transplant-eligible NDMM pts. To determine whether D-VRd demonstrates efficacy and tolerability in NDMM pts for whom transplant is not intended as initial therapy, the phase 3 CEPHEUS study will evaluate the efficacy and safety of D-VRd vs VRd alone in this pt population. Methods: This is an ongoing multicenter, open-label, randomized phase 3 study of D-VRd vs VRd alone in pts with NDMM for whom transplant is not intended as initial therapy. Approximately 360 pts will be stratified by ISS stage and age/transplant eligibility (age < 70 years and transplant-ineligible, or age < 70 years and refusal to transplant, or age ≥70 years) and will be randomized in a 1:1 ratio. All pts will receive eight 21-day cycles of VRd (V: 1.3 mg/m 2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-14; d: 20 mg PO/IV Days 1, 2, 4, 5, 8, 9, 11, 12), followed by 28-day cycles of Rd (R: 25 mg PO Days 1-21; d: 40 mg PO/IV Days 1, 8, 15, 22) until progressive disease (PD). Patients in the DARA group will also receive subcutaneous DARA (1,800 mg co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; Halozyme]) weekly in Cycles 1-2, every 3 weeks in Cycles 3-8, and every 4 weeks in Cycles 9+ until PD. All pts will receive preinfusion medications. Minimal residual disease (MRD)-negative rate at 10 –5 sensitivity threshold by NGS is the primary endpoint. MRD will be evaluated at suspected complete response or better. Secondary endpoints include progression-free survival (PFS), MRD-negative rate at 1-year, durable MRD negativity, overall response rate, time to and duration of response, PFS on next line of therapy, overall survival, clinical efficacy in high-risk molecular subgroups, health-related quality of life, pharmacokinetics, immunogenicity, and safety. Clinical trial information: NCT03652064