Talquetamab and Teclistamab in RRMM: Updated Results from RedirecTT-1 | Yael Cohen, MD | IMS 2024

So hi, my name is Yael Cohen and I'm a myeloma physician practicing in Tel Aviv Medical Center in Israel. And this morning I reported here at IMS Rio the results from the Redirect 1 study which I would like to share with you. So Redirect is actually the first study ever to combine together two bispecific antibodies for the treatment of myeloma. So these were teclistumab which is a bispecific targeted towards BCMA target and talcuetumab which is targeted towards GPRC5D. So both of these drugs have been approved recently for the treatment of myeloma to be taken alone, that is as a monotherapy. But what is unique in this study is that they are combined together and really the rationale for combining two drugs bispecific antibodies to treat myeloma is twofold. First we want to increase the likelihood of hitting the myeloma. So we know there is some heterogeneity, some myeloma cells might express one antigen and some might express the others. So if we are targeting two ways of them at once, we have a greater likelihood to be able to eradicate more of the tumor. But I think the most important thing is actually that we are avoiding tumor escape. We are avoiding tumor escape, that is when we are treating myeloma sometimes one of the cells develops some kind of mutation, some kinds of change and learns how to actually avoid the drug under our therapeutic pressure. But if we are targeting two antigens simultaneously the likelihood of a cell being able to escape and to make these two modifications in the exact same time is really lower. So that can probably translate into a longer effect of a drug or a longer durability of our response. So the findings in this study, we were reporting today 94 patients who were enrolled in this study and this was a phase one study. So we started with cohorts with lower doses and then went up gradually to confirm what is the right dose that works best also in terms of safety, the recommended phase two regimen. We had 44 patients in that recommended regimen and what we saw in terms of safety, safety was in general manageable. The CRS, the cytokine release syndrome and the neurologic effects were no different than those reported for each of the drugs. Also infection wise in the recommended phase two dose actually the rate of severe infections was very close to that, it was reported in each of the individual drugs. Moving towards the efficacy, so here the results were really very encouraging. The overall response rate, so this was very high around 80% in the entire patient population. In those specific hard to treat patients who have what we call extramederal disease, that is disease that actually lost its dependence in the bone marrow. So these are myeloma tumors that are outside of the bone marrow and are even not contingent with any bone, that means they spread through the blood to form a tumor. We know this is very very hard to treat a group of patients and their outcomes tend to be really poor even with the newer drugs, even with CAR T actually or with the bi-specifics given individually, the results are still compromised and here we were really encouraged to see that the response rate for these EMD patients was 61%. This is double what was ever reported with other modalities including CAR T, but I think the most important finding in our study was the durability of the responses. So the responses were long, patients who responded kept their response for extended periods of time and we have an 18 month report of durability of response and in the entire patient population this was as high as the 86%. So it means the patient who responded after a year and a half there was an 86% likelihood this patient remained in response and what's also very encouraging is the durability of response in the EMD patients here. We have a shorter follow-up so we're reporting the 12 month durability of response and this was 61%. Again this is double what was ever reported day before. So I think you know when you test the new combination if you give it like the highest bar the toughest patients and you see the effect there that gives you a really a good sense of what is the advantage comparison to other treatments and what is the real potency. So I think this is a leap forward very encouraging for our patients and indeed there has been another part of the study not yet reported dedicated only to EMD patients. This is the phase two of the redirect it just completed its enrollment so we're looking to see how this will read out and there's also a phase three trial in monumental six which is comparing the TALTEK combination with other arms with TALPOS pomalidomide and with the position's choice of the standard of care. So I think these are encouraging news for our patients and hopefully this will allow us to get a greater disease control for a longer period of time. Thank you.