Recurrent Multiple Myeloma

GSK's latest Blenrep data, presented at the American Society of Clinical Oncology 2024 annual meeting in Chicago, marked the second positive phase 3 readout for the multiple myeloma antibody-drug conjugate. Armed with two positive phase 3 trial readouts and the hope that at least one will show a significant patient survival benefit, GSK thinks it has the data to convince doctors and the FDA that the once-failed antibody-drug conjugate (ADC) Blenrep can work in multiple myeloma. In a second phase 3 win, Blenrep cut the risk of cancer progression or death by 48% compared with Takeda’s Velcade (V) in their respective combinations with Bristol Myers Squibb’s Pomalyst (P) and the steroid dexamethasone (d). The results came from the DREAMM-8 trial conducted in multiple myeloma patients who had tried at least one prior line of therapy and were shared at the American Society of Clinical Oncology 2024 annual meeting. After a median follow-up of 21.8 months, the median progression-free survival (PFS) was still not reached for the Blenrep arm, versus 12.7 months for control. The latest data set follows a recent readout from the DREAMM-7 trial, in which Blenrep beat Johnson & Johnson’s Darzalex (D) by 59% on PFS in their respective pairings with Vd. That study also tested the regimens in the second line or later. With the two positive trials, GSK plans to file Blenrep with the FDA in the second half of this year, Hesham Abdullah, M.D., GSK’s head of oncology R&D, told Fierce Pharma. The company hopes to reintroduce Blenrep in the U.S. following a market withdrawal in the late-line setting, which was triggered by the drug’s phase 3 flop as a monotherapy. During an ASCO press briefing on Saturday, Suzanne Trudel, M.D., from Princess Margaret Cancer Centre in Canada, who presented the DREAMM-8 results, and Oreofe Odejide, M.D., an ASCO-invited expert from Dana-Farber Cancer Institute, said the data support Blenrep’s return as a treatment option for relapsed myeloma. If approved, Blenrep, a BCMA-directed ADC, will compete with J&J and Legend Biotech’s powerful BCMA CAR-T therapy, Carvykti, in second-line treatment, plus BMS' rival CAR-T, Abecma, in later lines. By a cross-trial comparison, the 48% PFS benefit seen in Blenrep’s latest DREAMM-8 study looks smaller than the 59% result recorded by Carvykti in its CARTITUDE-4 trial. The Carvykti study used PVd or DPd in the control group. Abdullah said GSK is optimistic that the earlier DREAMM-7 study will be able to meet statistical significance on overall survival. At a prior interim analysis, Blenrep-Vd preliminarily pared down the risk of death by 43% versus PVd. At the time, the showing just narrowly missed statistical significance. By comparison, J&J’s Carvykti was also linked to a preliminary 43% reduction in the risk of death versus PVd or DPd during a recent data cut, although that number remained immature. Bristol Myers’ Abecma, in a third-line setting, didn’t show any patient survival benefit in the phase 3 KarMMa-3 study without adjusting for patient crossovers. Given the progress of that study, the FDA figured it’s unlikely that the BMS trial will eventually hit statistical significance on overall survival. As for the current DREAMM-8 trial, Blenrep showed a favorable trend toward a 23% reduction in the risk of death at the interim analysis. GSK expects the size of benefit will widen over time, Abdullah said, without expressing the same level of confidence on reaching statistical significance. Abdullah also flagged some important differences between the trials. In DREAMM-7, about half of the trial participants had tried BMS’ Revlimid, including 30% who were refractory to the immunomodulating agent. In DREAMM-8, all patients had previously tried Revlimid, including 80% who were refractory. Besides the trials' efficacy results, there’s the CAR-T therapies’ known drawbacks around lengthy manufacturing timelines and complicated administration procedures. The drugs are required to be given at designated treatment centers. Both CAR-T trials recorded an early risk of death for patients in the cell therapy groups. As the early death cases were mostly seen in patients who didn’t live long enough to receive their assigned CAR-T therapies, the FDA has argued that these individualized medicines’ production timelines were to blame. Conversely, Blenrep didn’t have that early death signal. As an off-the-shelf therapy, it could be more accessible to patients in the community setting, where more than 70% of myeloma patients are currently treated, Abdullah noted. “Access, consistency of treatment effects and that effect across multiple patient subgroups, and overall survival” will be the key differentiators for Blenrep, the GSK exec said. Based on the positive results in previously treated patients, both J&J/Legend and BMS have kicked off phase 3 trials for their CAR-Ts in the first-line setting. GSK is taking a pause to dig into Blenrep’s existing data and mull over its earlier-line strategy, Abdullah said.

This conclusion is the result of almost 10 years of research carried out by the International Myeloma FoundationSTUDIO CITY, Calif., April 12, 2024 (GLOBE NEWSWIRE) -- The International Myeloma Foundation (IMF) is exhilarated to share that through the leadership of the organization’s Chief Scientific Officer Dr. Brian G.M. Durie and the presentations from members of the collaborative research group, the i2TEAMM, the Oncologic Drug Advisory Committee (ODAC) unanimously voted in favor (12-0) of using minimal residual disease (MRD) as an early endpoint for accelerated approval in multiple myeloma clinical trials. This means that the FDA may approve multiple myeloma drugs in the development pipeline much sooner. To date, many myeloma drug approvals take 9-12 years and must demonstrate a progression-free survival of 5-8 years. With MRD testing as an early endpoint in clinical trials, researchers can reliably predict progression-free survival and overall survival for multiple myeloma patients, making it a precise early endpoint. The IMF’s President and CEO, who is also a 28-year myeloma survivor, Yelak Biru said, “On the heels of the FDA approvals for two CAR T-cell therapies in the relapsed setting of myeloma, I am thrilled to learn that today’s ODAC meeting will only continue to support the expansion of available treatment options for multiple myeloma patients. It is the IMF’s vision to meet patients where they are in the stage of their disease and to realize a world where every myeloma patient can live life to the fullest, unburdened by this disease.” At this morning’s ODAC meeting, IMF Chief Scientific Officer Brian G.M. Durie, MD (Cedars-Sinai Samuel Oschin Cancer Center) along with his colleagues Bruno Paiva, PhD (University of Navarra – Navarra, Spain); Dr. Qian Shi, PhD; (Mayo Clinic – Rochester, MN); and Kenneth C. Anderson, MD (Dana-Farber Cancer Institute and Harvard Medical School — Boston) gave testimonials at the ODAC meeting on approving minimal residual disease (MRD) testing as an early endpoint for the accelerated approval of multiple myeloma drugs in clinical trials. ODAC is a specialized group that operates under the U.S. Food and Drug Administration (FDA). The committee's primary role is to review and evaluate data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer. Composed of 12 voting members, the ODAC plays a crucial role in the evaluation of new drugs, making recommendations concerning these drugs. The committee's assessments and recommendations are then forwarded to the Commissioner of Food and Drugs. This process ensures that any new oncologic drugs brought to market have been thoroughly reviewed and evaluated for their safety and effectiveness. Dr. Durie submitted an independent new drug application to ODAC on behalf of the IMF. He cited the IMF’s collaboration with the i2TEAMM (or, the International Independent Team for Endpoint Approval in Multiple Myeloma). This collaborative research group along with the IMF has spent nearly 10 years compiling the largest data sets to support the use of MRD as an endpoint for accelerated approval of myeloma drugs in the frontline settings of transplant-eligible, newly diagnosed multiple myeloma and non-transplant eligible, newly diagnosed multiple myeloma as well as for relapsed myeloma. These efforts on the part of Dr. Durie and the i2TEAMM align with the IMF’s mission to improve the quality of life of myeloma patients while working toward prevention and a cure. The IMF is committed to increasing treatment options for patients to ensure they have the best care at the best time during their disease. ABOUT MULTIPLE MYELOMA Multiple myeloma is a cancer of the bone marrow plasma cells — white blood cells that make antibodies. A cancerous or malignant plasma cell is called a myeloma cell. Myeloma is called “multiple” because there are frequently multiple patches or areas in bone where it grows. It can appear as both a tumor and/or an area of bone loss, and it affects the places where bone marrow is active in an adult: the hollow area within the bones of the spine, skull, pelvis, rib cage, and the areas around the shoulders and hips.   ABOUT THE INTERNATIONAL MYELOMA FOUNDATION     Founded in 1990, the International Myeloma Foundation (IMF) is the first and largest global foundation focusing specifically on multiple myeloma. The Foundation’s reach extends to more than 525,000 members in 140 countries worldwide. The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure by focusing on four key areas: research, education, support, and advocacy. The IMF has conducted more than 250 educational seminars worldwide, maintains a world-renowned InfoLine, and in 2001, established the International Myeloma Working Group (IMWG), a collaborative research initiative focused on improving myeloma treatment options for patients. In 2012, the IMF launched the Black Swan Research Initiative®, a groundbreaking research project aimed at curing myeloma. The IMF can be reached at (800) 452-CURE (2873). The global website is www.myeloma.org. Follow the IMF on:X: @IMFmyelomaInstagram: @imfmyeloma Facebook: @myeloma LinkedIn: International Myeloma Foundation Media Contacts: Peter AntonPanton@myeloma.org Jason LondonJlondon@myeloma.org

• HPN217 was well tolerated and demonstrated robust and durable clinical activity at doses ranging from 2.15 to 24 mg in heavily pre-treated patients, including patients with prior exposure to BCMA-targeted therapy • At the 12 mg dose, cohorts demonstrated favorable activity and safety profile: - 63% ORR; with 53% VGPR or better - - CRS reported in 16% of patients, no Grade 3 events, no ICANS - • Findings support further clinical development at the 12 mg RP2D Harpoon Therapeutics, Inc. (Nasdaq: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, today reported data from the Phase 1 study of HPN217 in patients with RRMM in an oral presentation at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego. Harpoon also announced the selection of 12 mg as the HPN217 RP2D. During the trial, 97 patients with RRMM who had received at least three prior therapies were enrolled across 15 dose escalation cohorts and three expansion regimens. As of the data cut-off of October 17, 2023, the data demonstrated: Clinical activity across a wide dose range (2.15 mg to 24 mg). The maximum tolerated dose (MTD) was not reached at the target dose using a step up approach. Optimal activity and safety profile was seen at 12 mg, which was declared the RP2D. The Overall Response Rate (ORR) across 12 mg cohorts was 63% (12/19, 95% CI: 38, 84). In addition, the depth of response was most significant at 12 mg, with 53% (10/19) of patients having a Very Good Partial Response (VGPR) or better. The median time to first response in the 12 mg and 24 mg cohort was 1.2 months, and the median duration of response for all responders was 20.5 months as of the data cutoff date. Out of all the responders, 58% (22/38) remain on treatment. In the 12 mg and 24 mg cohorts, nine patients were previously exposed to BCMA-targeting agents, and six of those patients responded to the HPN217 treatment. The incidence of cytokine release syndrome (CRS) was lowest (16%) in the 12 mg cohorts, all Grade 1-2. No immune effector cell associated neurotoxicity syndrome (ICANS) events were observed at the 12 mg dose. “The data presented at ASH today demonstrates that HPN217 has the potential to provide a meaningful benefit for patients with relapsed/refractory multiple myeloma, even in patients with prior anti-BCMA therapy,” said Sumit Madan, M.D., Hematologist and Oncologist at Banner MD Anderson Cancer Center and Associate Professor (Adj) of Myeloma and Lymphoma at UT MD Anderson Cancer Center. "The low rate of CRS seen in this study is noteworthy and can help enable future studies of HPN217 in combination and in earlier lines of therapy.” “The HPN217 Phase 1 data set represents important progress for the program and validates the potential of HPN217 to deliver a wider therapeutic index. We observed a compelling 63% response rate in patients treated with the 12 mg target dose, with only a 16% rate of CRS,” said Luke Walker, M.D., Chief Medical Officer for Harpoon Therapeutics. “These data and our interactions with the FDA have enabled us to declare a RP2D that can be used to support further clinical development.” HPN217 targets B-cell maturation antigen (BCMA) and is based on Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC®) platform designed to recruit a patient’s own immune cells to kill tumor cells. BCMA, a clinically validated target, is a tumor necrosis factor receptor super family member and is a receptor protein expressed on nearly all multiple myeloma cells. Harpoon Therapeutics is a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases. T cell engagers are engineered proteins that direct a patient’s own T cells to kill target cells that express specific proteins, or antigens, carried by the target cells. Using its proprietary Tri-specific T cell Activating Construct (TriTAC®) platform, Harpoon is developing a pipeline of novel TriTACs initially focused on the treatment of solid tumors and hematologic malignancies. Harpoon has also developed a proprietary ProTriTAC™ platform, which applies a prodrug concept to its TriTAC platform to create a therapeutic T cell engager that remains inactive until it reaches the tumor. Harpoon’s third proprietary technology platform, extended release TriTAC-XR, is designed to mitigate cytokine release syndrome. For additional information about Harpoon Therapeutics, please visit www.harpoontx.com. The content above comes from the network. if any infringement, please contact us to modify.