At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, Yael C Cohen, MD, Tel-Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel presented results of the RedirecTT-1 trial, a phase 1n trial of the combination of teclistamab and talquetamab targeting bispecifics BCMA and GPRC5D for the treatment of patients with relapsed/refractory (R/R) multiple myeloma (MM.)

Notably, this was the first time that data combining 2 bispecifics for treatment of a hematological malignancy has been reported.

Transcript:

Hi. I'm Yael Cohen. I'm a [hematologist-oncologist] from the Tel-Aviv Sourasky Medical Center in Israel and I'll be presenting today the results of the RedirecTT-1 trial, which is a phase 1b trial of the combination teclistamab and talquetamab for the treatment of patients with relapsed/refractory multiple myeloma. 

This is actually the first time ever that the data combining two bispecifics for treatment of a hem malignancy has ever been reported. So that's really exciting. So, with the RedirecTT-1 trial, it was a phase 1b and it included a dose-escalation strategy with a step-up dosing at each dose to identify the recommended phase 2 regimen, or RP2R, which was identified at the dose of 3mg per kg of teclistamab and 0.8 [mg per kg] of talquetamab.

Overall, 93 patients were enrolled in the study. Of them, 34 were in the RP2R. The median age was 65 and the number of prior lines of therapy was a median of 4. And these were really tough patient cohorts, so about a third of the patients had extramedullary soft tissue plasmacytoma and this is known as hard to treat in patients. 25% had prior BCMA exposure. 75% were actually triple-class refractory and almost 90% of the patients were refractory to their last line of therapy. 

So as far as safety, the top message is really that there were no new safety concerns and the safety was comparable to that of each of the monotherapies. So as far as hematologic toxicities, the most frequent was neutropenia. However, only 12.9% of the patients had febrile neutropenia. Non-hem toxicities, there were mostly infections. However, less than 40% of the patients at RP2R had grade 3 to 4 infections. There were 6 deaths due to infection on the study.

As far as mitigating these infections, it should be mentioned that the hypogammaglobulinemia was very prevalent—over 80% of the patients. Less than half of the patients received IVig [intravenous immunoglobulins], which is recommended according to institutional guidelines to mitigate these infections and so perhaps safety could be further improved by broader implementation of this measure. CRS was mostly grade 1 and 2 and it occurred early during the treatment in step up, or in the first cycle. 26% of the patients required tocilizumab to manage this adverse event. There were no discontinuations or deaths due to CRS. 

So switching to the efficacy, in a total of 14 months of follow up for the entire cohort and then 8 months for the RP2R, the overall response rates were very high for this tough to treat refractory population. We're looking at an 86% overall response rate for the entire cohort and up to 96% for the RP2R patients. And these responses were durable, so at data cut-off, 61% of the patients were still on therapy and the median duration of response was not reached. And the responses were also rapid, occurring at around 2 months and the best response was achieved around 4 months and progression-free survival for the entire cohort was over 20 months. 

If we're diving into the patients with extramedullary disease—and these are really tough to treat patients—we know from other off-the-shelf measures treating these patients that responses are expected between 5% to 40%. CAR-Ts do a little better with high response rates, but unfortunately, those responses are limited in their duration. And here with the combination, we found that 85% of the patients at the RP2R had the responses of these soft tissue plasmacytomas. It's important to focus that these are not paraskeletal lesions, but real soft tissue plasmacytomas. So that is really a very encouraging result, and these responses were very durable, actually not reached the duration of response in the RP2R. 

This is the first combination of 2 bispecifics ever to be reported in hem malignancies and the rates of overall response in this very high-risk myeloma population were as high as 96%, and this is comparable only by CAR-Ts in this treatment population. The safety was manageable and comparable to monotherapies, and these encouraging results lead to further investigations of this combination. There's actually further studies planned and then an expansion cohort for extramedullary disease is going to open soon for RedirecTT-1. Thank you for your attention.

Source:

Cohen Y, Morillo D, Gatt M E, et al. First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Presented at ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 8002.