DARZALEX® Study Data Show High Response Rate

The Janssen Pharmaceutical Companies of Johnson & Johnson announced results from the randomized Phase 2 GRIFFIN (MMY2004) study showing that the addition of DARZALEX® (daratumumab) to bortezomib, lenalidomide and dexamethasone (VRd) induced higher response rates in newly diagnosed patients with multiple myeloma who were eligible for high-dose therapy and autologous stem cell transplantation (ASCT) compared with VRd alone.

"The GRIFFIN study is the second randomized study to investigate the benefit of daratumumab for patients with newly diagnosed multiple myeloma who are eligible for a transplant, and the first in combination with lenalidomide for this population," said Peter M. Voorhees, M.D., GRIFFIN principal investigator at Levine Cancer Institute. "This study adds to the growing body of evidence for the addition of daratumumab to proteasome inhibitor/immunomodulatory combination therapy in the transplant setting."

Results from the Phase 2 GRIFFIN study showed that by the end of six cycles of therapy and transplant, a greater percentage of patients receiving DARZALEX®-VRd achieved the primary endpoint of stringent complete response (sCR) compared with VRd alone (42 percent vs. 32 percent, respectively; Odds Ratio [OR] = 1.57; 95 percent confidence interval [CI], 0.87-2.82; P=0.1359), meeting the prespecified 2-sided alpha of 0.2 for a positive study. The addition of DARZALEX® to VRd resulted in higher rates of overall response (99 percent vs. 92 percent), very good partial response or better (91 percent vs. 73 percent) and complete response (CR) or better (52 percent vs. 42 percent) compared with VRd alone, respectively. Notably, the rate of minimal residual disease (MRD) negativity among patients achieving a CR or better more than doubled in the DARZALEX®-VRd arm compared with VRd alone (59 percent vs. 24 percent). The most common (≥10 percent) Grade 3/4 treatment-emergent adverse events (TEAEs) for DARZALEX®-VRd were neutropenia (32 percent), lymphopenia (23 percent), thrombocytopenia (16 percent) and leukopenia (15 percent). Grade 1/2 infections occurred more frequently in the DARZALEX®-VRd arm, but there was no difference in the rate of Grade 3/4 infections between the DARZALEX®-VRd and VRd arms. Infusion-related reactions (IRRs) occurred in 41 percent of patients who received DARZALEX®-VRd, which were primarily Grade 1/2 and during the initial infusion.

"This primary analysis of the GRIFFIN study builds on the safety and efficacy data in the initial group of 16 patients presented at the 2018 American Society of Hematology Annual Meeting," said Andree Amelsberg, M.D., MBA, Vice President, Oncology Medical Affairs, Janssen Biotech, Inc. "It provides further support for evaluation of DARZALEX® in the transplant-eligible patient population, which is important as we continue our work to discover new therapeutic approaches to improve outcomes for patients."

In addition to GRIFFIN, data from the Phase 2 PLEIADES (MMY2040) study, presented during an oral session at the IMW meeting, showed that an investigational DARZALEX® subcutaneous (SC) formulation delivered in combination with standard-of-care treatment regimens showed similar clinical activity and safety to DARZALEX® intravenous (IV) regimens. The study is the first to evaluate SC DARZALEX® in different combination regimens for patients with newly diagnosed multiple myeloma as well as those who were relapsed/refractory to current treatment options.

"We're excited about the opportunity to progress the innovation represented by the DARZALEX® subcutaneous formulation, which can be administered over the course of minutes and has the potential to offer a reduction in infusion-related events as compared to the approved intravenous formulation," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development. "Data from the PLEIADES study demonstrates that the DARZALEX® subcutaneous formulation can also be safely administered in combination with standard backbone regimens used for treatment naïve and relapsed/refractory patients with multiple myeloma. It has been included in our recent submission of a Biologics License Application to the U.S. Food and Drug Administration seeking approval of a new DARZALEX® subcutaneous formulation for patients with multiple myeloma."

Results from the PLEIADES study showed the median duration of administration was 5 minutes across all cohorts, compared with more than 3 hours with IV infusions. Rates of any grade IRRs and injection-site reactions were 7.5 percent across all cohorts, with one Grade 3 IRR in one cohort and no Grade 4 IRRs. Grade 3/4 TEAEs were reported by more than 50 percent of patients across cohorts, and TEAEs leading to treatment discontinuation were less than 8 percent in all cohorts. Safety profiles in all cohorts were consistent with the IV administration of DARZALEX® in combination with these regimens.

The open-label Phase 2 GRIFFIN (MMY2004) study has enrolled and treated adult patients, age 29-70 years, with newly diagnosed multiple myeloma who were eligible for high-dose therapy/ASCT, including 16 patients in a safety run-in phase and more than 200 patients in the subsequent randomized portion of the study. During induction (Cycles 1-4) and consolidation (Cycles 5-6) in the randomized part of the study, all patients received 25 mg of lenalidomide orally on Days 1-14, 1.3 mg/m2 of bortezomib subcutaneously on Days 1, 4, 8 and 11, and 20 mg of dexamethasone on Days 1, 2, 8, 9, 15 and 16 every 21 days. In the DARZALEX®-VRd arm, DARZALEX® 16 mg/kg IV was given on Days 1, 8 and 15 of Cycles 1-4 and on Day 1 of Cycles 5-6. During maintenance (Cycles 7-32), all patients received 10 mg daily of lenalidomide (15 mg beginning at Cycle 10 if tolerated) on Days 1-21 every 28 days. In the DARZALEX®-VRd arm, DARZALEX® 16 mg/kg IV was given every 56 days; this has been amended to give DARZALEX® every 28 days based on emerging pharmacokinetic data. Maintenance therapy with lenalidomide may be continued beyond Cycle 32 per local standard of care.

The non-randomized, open-label, parallel assignment Phase 2 PLEIADES (MMY2040) study included 199 adults with either newly diagnosed or relapsed/refractory multiple myeloma. Patients with newly diagnosed multiple myeloma were treated with 1,800 mg of the SC formulation in combination with either bortezomib, lenalidomide and dexamethasone (D-VRd) or bortezomib, melphalan and prednisone (D-VMP). Patients with relapsed or refractory disease were treated with 1,800 mg of the SC formulation plus lenalidomide and dexamethasone (D-Rd). The primary endpoint for the D-VMP and D-Rd cohorts was overall response rate. The primary endpoint for the D-VRd cohort was very good partial response or better rate. An additional cohort of patients with relapsed and refractory multiple myeloma treated with daratumumab plus carfilzomib and dexamethasone was subsequently added to the study.

DARZALEX® (daratumumab), the first CD38-directed antibody approved anywhere in the world, is the only CD38-directed antibody approved to treat multiple myeloma. CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease. DARZALEX® binds to CD38 and inhibits tumor cell growth causing myeloma cell death. DARZALEX® may also have an effect on normal cells. DARZALEX® is being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant hematologic diseases in which CD38 is expressed, such as smoldering myeloma.

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow. When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow. In 2019, it is estimated that 32,110 people will be diagnosed and 12,960 will die from the disease in the U.S. While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, tiredness, high calcium levels, kidney problems or infections.

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