LINKER-MM1 Study in RRMM | Naresh Bumma, MD | ASH 2022

Hi, my name is Nourish Brahma and I'm part of the multiple myeloma and myelomidosis group at The Ohio State University James Cancer Center. And I would like to talk about the Linker MM1 study, which is a phase 1-2 study of Regeneron 5458, now called Limva-Saltimab in relapsed refractive multiple myeloma. As we have more and more agents being brought to the first line, the sphere of treating relapsed refractive multiple myeloma has become more complex and more interesting. And the emergence of specific T-cell angager antibodies has been sort of pivotal and I believe game-changing in this sphere. B-cell maturation agent or BCMA is one of the most promising targets for treating multiple myeloma and is being targeted using antibody drug conjugates, CAR T-cell, and most importantly, bicepastic T-cell engagers. So Limva-Saltimab or Regeneron 5458 is a bicepastic antibody linking BCMA with CD3 made on the Velocivector platform by Regeneron. We had at last, Ash presented the phase 1 study looking at the safety analysis for this compound where we had enrolled patients with relapsed refractive multiple myeloma and had five doses that patients were dosed upon in a dose escalation pattern. The recommended dose for the phase 2 was 200 milligrams and we'll now discuss the results from it. So this was a fairly heavily predated population. 99 percent of them were triple exposed and 83 percent were penta exposed. 81 percent were triple refractory and 37 were penta refractory. The patients had a significantly high disease of burden with 37 of them having more than 50 percent plasma solenoid bone marrow and a serum BCMA median level of .43. So two doses were explored in the phase 2 cohort, 50 milligrams and 200 milligrams. The safety data is actually fairly interesting. We only saw 44 percent of CRS which occurred predictably with a median of 11 hours after infusion and resolved with a median of 15 hours afterwards. The median tosillizumabuse was only 14 percent of patients. Looking at ICANNs that was seen only 5.6 percent of patients. Infections were seen in 54 percent of patients but only 29 percent had grade 3 or more infections which means severe infections that require admission to the hospital with IV antibiotics or IC state. Opportunistic infections which are described as infections not usually seen in patients multiple myeloma for example, pneumocystis pneumonia or viral infection with a virus called CMV was seen in about 4 percent of patients and severe infections as rated at great few or more were only seen in 3 percent of patients. The efficacy data, the overall response rate in the phase 2 cohort was 64 percent with 45 percent being VGPR better. In patients who were accessible for MRD, MRD was seen in 60 percent of patients. It is interesting that some patients who were on the 50 milligram cohort had an intrapatient dose escalation to 200 milligram when they were found to be not responding and out of the 8 patients who did undergo that 6 patients of them had a response. So kind of to summarize we have this cohort of highly disease burden patients with more than 37 percent having 50 percent of more plasma cell, serum-based level 0.43 which is pretty high and who are fairly far along in the course with 84 percent of them being Penta exposed with a response rate of 64 percent and a very manageable toxicity profile with CRS of only 44 percent. So I believe that this is a very exciting data set from this specific product and we are looking to explore this further in multiple myeloma with a newer trial called Linker MM2 which will be coming out looking at this compound in combination with other drugs such as Dr. Tumumab, Garfalsumab, Lenalidomide and Pomalidomide. Thank you.