Belantamab mafodotin

Pictured: GSK building in Dresden, Germany/iStock, 13threephotography GSK on Thursday reported a second Phase III win for its BCMA-directed antibody-drug conjugate Blenrep, boosting its prospects for getting the cancer drug back on the U.S. market. The FDA awarded accelerated approval to Blenrep (belantamab mafodotin) as a treatment for fourth-line multiple myeloma in 2020. However, the antibody-drug conjugate (ADC) failed the confirmatory Phase III trial in November 2022, leading the FDA to ask GSK to withdraw the drug from the U.S. market later that month. Since then, the drugmaker has continued studies in earlier-line patients that could potentially resurrect the product. GSK revealed one trial, DREAMM-7, hit its primary endpoint in November 2023 and shared additional data one month ago. Now, the company has reported the success of DREAMM-8, a head-to-head clinical trial that pitted a Blenrep-based regimen against the standard of care in second line and later multiple myeloma. All 302 patients received pomalidomide plus dexamethasone (PomDex). Investigators randomized people to receive either Blenrep or bortezomib, a molecule sold as Velcade, on top of the PomDex backbone. Progression-free survival was significantly longer in the Blenrep cohort than the control arm at a prespecified interim analysis, prompting the independent data monitoring committee to recommend the early unblinding of the data. GSK is yet to share any data but said the Blenrep regimen “significantly extended the time to disease progression or death versus the standard of care combination.” The company also reported a positive overall survival (OS) trend favoring Blenrep. The wording suggests the OS endpoint was not statistically significant at the interim analysis but that could change as the data matures. GSK is continuing to track patients for OS. A filing to get Blenrep back on the U.S. market could be next. GSK plans to discuss data from the two successful Phase III clinical trials with regulators. Hesham Abdullah, global head of oncology R&D at GSK, said in a statement the Blenrep combinations “have the potential to redefine the treatment of relapsed or refractory multiple myeloma.” GSK will gain a clearer picture of the potential of the combinations as the OS data matures. If GSK’s Blenrep comes to market, it will face intense competition from BCMA-directed CAR-T cell therapies and T-cell engagers already competing for multiple myeloma market share against molecules that hit other targets. Should GSK work through the challenges, Blenrep could enable the company to beat its current mid-term forecasts. The drugmaker raised its 2031 sales target in January but excluded Blenrep from its outlook. Sales of the product crashed after GSK withdrew it from the U.S., falling to £36 million ($46 million) last year. Nick Paul Taylor is a freelance pharmaceutical and biotech writer based in London. He can be reached on LinkedIn.

The company plans for a Phase I dose-escalation and dose-expansion study with CLN-619. Credits: Lightspring/Shutterstock.com Cullinan Oncology is gearing up to advance one of its lead drugs CLN-619 into a Phase I clinical study for multiple myeloma following US Food and Drug Administration (FDA) clearance of its Investigational New Drug (IND). According to the 1 March press release, the planned Phase I study will comprise of a dose escalation and dose expansion phase testing CLN-619 as a potential treatment for relapsed or refractory multiple myeloma. CLN-619, an intravenously administered anti-MICA humanized IgG1 monoclonal antibody, is designed to inhibit MHC class I polypeptide related sequence A (MICA) and MHC class I polypeptide related sequence B (MICB) to induce activation of natural killer group 2D (NKG2D) receptors. In engaging these receptors, CLN-619 is hypothesised to promote the cytotoxicity and lysis of NK-mediated tumour cells. As per Cullinan CMO Dr. Jeffrey Jones, CLN-619 is capable of restoring MICA/B expression on tumor cells and enabling immune recognition. The Phase I study will be the first MICA/B antibody clinical study in hematologic malignancies, according to the company. The Cambridge, Massachusetts-based biotech is also evaluating CLN-619 as a monotherapy and in combination with MSD’s Keytruda (pembrolizumab) in a Phase I study (NCT05117476) for advanced solid tumours. Cullinan expects “updated” clinical data in Q2 2024. See Also: Market cap upturn for top 20 biopharma companies with obesity drug successes in 2023 Lutris wins FDA orphan drug tag for EGFR inhibitor-induced rash candidate Cullinan is far from being the only company playing in the multiple myeloma space. Last month, Starton Therapeutics announced that it had activated another site for its Phase Ib STAR-LLD study (NCT06087653) that is evaluating a continuous subcutaneous low-dose lenalidomide in combination with dexamethasone and Takeda’s Velcade (bortezomib). Also in February, GSK published interim results from the Phase III DREAMM-7 study assessing a combination treatment comprised of its antibody drug conjugate Blenrep (belantamab mafodotin) alongside bortezomib and dexamethasone (BorDex) in a head-to-head comparison against a combination with Janssen Oncology’s Darzalex (daratumumab). The study reported that it found significant improvements in progression free survival (PFS) in patients with relapsed or refractory multiple myeloma.