Teclistamab

THURSDAY, Jan. 9, 2025 -- For patients with relapsed or refractory multiple myeloma, talquetamab plus teclistamab shows response in a high percentage of patients and a higher incidence of grade 3 or 4 infections than with either therapy alone, according to a study published in the Jan. 9 issue of the New England Journal of Medicine . Yael C. Cohen, M.D., from the Tel Aviv Sourasky Medical Center in Israel, and colleagues conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. Five dose levels were investigated in a dose-escalation study in phase 1. The recommended phase 2 regimen was talquetamab at a dose of 0.8 mg/kg body weight plus teclistamab at a dose of 3.0 mg/kg every other week. The primary objective of the study was to evaluate adverse events and dose-limiting toxic effects. Ninety-four patients received treatment; 44 used the recommended phase 2 regimen. Patients were followed for a median of 20.3 months. The researchers found that three patients had dose-limiting toxic effects (including one with grade 4 thrombocytopenia, who received the recommended phase 2 regimen). The most common adverse events across all dose levels were cytokine release syndrome, neutropenia, taste changes, and nonrash skin events. Ninety-six percent of patients had grade 3 or 4 adverse events, most often hematologic events. Sixty-four percent of patients had grade 3 or 4 infections. A response occurred in 80 percent of the patients with the recommended phase 2 regimen and in 78 percent across all dose levels. The likelihood of patients continuing in response at 18 months was 86 and 77 percent with the recommended phase 2 regimen and across all dose levels, respectively. "On the basis of these results, this dual-targeting, off-the-shelf combination therapy warrants further investigation in patients with relapsed or refractory multiple myeloma," the authors write. The study was funded by Janssen, which manufactures talquetamab and teclistamab.

A GSK multiple myeloma medicine that was pulled from the market after failing its confirmatory test has new data from a Phase 3 study evaluating it an earlier line of treatment, and the latest results show the drug is helping patients live longer compared to a standard drug regimen. Clinical trial investigators and the company believe these results could support making the GSK drug, Blenrep, a new standard of care treatment for this type of blood cancer. The new trial results for Blenrep were presented Monday during the annual meeting of the American Society of Hematology. The FDA is reviewing data from the drug’s full Phase 3 program, which tested the drug head to head against two standard of care multiple myeloma drug regimens. An FDA decision is expected in July; Blenrep is also under regulatory review in six additional markets. While many treatments are available for multiple myeloma, frequent relapse in this type of blood cancer means patients need new treatment options that take different approaches to the disease. Blenrep is an antibody drug conjugate (ADC) designed to target BCMA, a protein abundant on the surface of multiple myeloma cells. The drug is administered as an intravenous infusion every three weeks. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech The Blenrep results presented Monday are from a Phase 3 test, DREAMM-7, that enrolled nearly 500 patients whose multiple myeloma relapsed or was refractory to at least one earlier line of therapy. The open-label study evaluated Blenrep in combination with bortezomib, brand name Velcade, and the corticosteroid dexamethasone, a standard multiple myeloma drug regimen typically shortened to BorDex. Blenrep and BorDex were compared against the CD38-targeting Johnson & Johnson multiple myeloma drug daratumumab, brand name Darzalex, combined with BorDex. The main clinical trial goal was measuring progression-free survival. On this endpoint, results showed the study drug achieved a median 36.6 months of progression-free survival versus a median 13.4 months in the comparator arm. On the key secondary goal of duration of response, results showed 40.8 months for the Blenrep arm, more than double the duration of the comparator. On overall survival, the median has not yet been reached in either arm, according to the primary analysis. But with a median follow-up of 39.4 months, GSK projects median overall survival for the Blenrep arm will be 84 months compared to 51 months for the comparator drug regimen. Dr. María-Victoria Mateos, principal investigator for DREAMM-7 and head of myeloma and clinical trials unit, hematology department, and professor of medicine at the University of Salamanca, Spain, sees the new Blenrep results as potentially practice changing. If the drug reaches the market, it could become a new standard of care drug regimen for relapsed and refractory multiple myeloma after at least one prior line of therapy, she said, speaking during a Monday briefing with journalists. In the same briefing, Hesham Abdullah, GSK’s senior vice president, global head oncology, highlighted the near tripling of progression-free survival achieved by Blenrep versus the comparator regimen, along with a strong duration of response to the therapy. He also noted the important marks for overall survival benefit — how long patients live while receiving treatment. Blenrep led to a 42% reduction in the risk of death versus the comparator. Abdullah noted this survival benefit is in line with results from an interim analysis reported earlier this year. Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News Blenrep’s 2020 accelerated FDA approval covered the use of the drug as a fifth-line multiple myeloma therapy, making it the first approved BCMA-targeting therapy. But after the drug, tested as a monotherapy, failed to show statistically signficiant improvement on the main goal of progression-free survival in its confirmatory Phase 3 test, GSK in 2022 withdrew the product from the market. Abdullah said that despite failing the confirmatory trial, results showed Blenrep was an active drug that behaved similarly to two other drug multiple myeloma combination regimens. The company proceeded to test Blenrep again, but as an earlier line of therapy and in combination with existing multiple myeloma therapies. In addition to the DREAMM-7 Phase 3 test against the Darzalex/BorDex combination, the Blenrep regimen was tested separately against the Bristol Myers Squibb drug Pomalyst and dexamethasone. In this Phase 3 study, DREAMM-8, results presented this past June during the annual meeting of the American Society of Clinical Oncology showed the Blenrep regimen led to a 48% reduction in the risk of disease progression or death. The multiple myeloma market has become more crowded in Blenrep’s absence. There are now two FDA-approved cell therapies that target BCMA: Abecma from Bristol Myers Squibb and 2SeventyBio, and Carvykti from Johnson & Johnson and Legend Biotech. Both were initially approved as fifth-line treatments. Earlier this year, the FDA expanded the approvals of both products, permitting Abecma to be used as a third-line therapy and Carvytki as a second-line treatment. J&J’s multiple myeloma portfolio also includes Tecvayli, a BCMA-targeting bispecific antibody. Besides Carvykti, the other BCMA-targeting therapies are approved only for use as later-line therapies, Mateos said. In the second-line setting, not all multiple myeloma patients will be eligible for a CAR T-cell therapy. Also, Carvykti, made by harvesting and engineering a patient’s own immune cells, takes weeks to manufacture, she said. By contrast, Blenrep provides multiple myeloma patients a readily available off-the-shelf treatment option. Abdullah added that Blenrep offers more flexibility compared with CAR T-therapy, which is offered only in certain hospitals equipped to administer these therapies and manage their complications. “We know that the majority of multiple myeloma patients sit within the community setting and oftentimes don’t have access to these more specialized technologies that require hospitalization and carry a different risk/benefit profile,” Abdullah said. Blurred vision and vision loss are known complication risks of ADCs as a drug class. When Blenrep was initially approved, its label carried a black box warning for ocular toxicity. GSK said eye-related side effects were generally manageable in the clinical trial and resolved with dose modification. These complications led to a discontinuation rate of about 10% in DREAMM-7. GSK has broader plans for Blenrep, which the company estimates could achieve £3 billion (about $3.8 billion) in peak sales. By comparison, J&J’s Darzalex posted $8.5 billion in revenue in the first nine months of 2024, a 19.3% increase compared to the same period in the prior year. GSK believes Blenrep could take some of the J&J product’s market share by securing additional approval as a first-line multiple myeloma treatment. A Phase 1 test is ongoing in newly diagnosed patients to identify the dose and drug combination to evaluate in a pivotal study. As GSK explores moving Blenrep into frontline use, Abdullah said the company is focused on improving the overall profile of the drug — maintaining efficacy while enhancing tolerability. Mateos said based on the DREAMM-7 data, BCMA is the better target than the CD38 target hit by Darzalex. The next step is comparing the two drugs in a first-line setting. Positive results for Blenrep could potentially change the treatment landscape for multiple myeloma, she said. Photo by GSK