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EHA 2021 | Update on Phase I trial of teclistamab in R/R myeloma

Niels van de Donk, MD, PhD, VU University Medical Center, Amsterdam, The Netherlands, gives an update on the Phase I MajesTEC-1 trial (NCT04557098) investigating the use of teclistamab monotherapy as a treatment for patients with relapsed or refractory (R/R) multiple myeloma administered either intravenously or subcutaneously. Teclistamab targets B-cell maturation antigen (BCMA) by redirecting CD3-positive T-cells to BCMA-expressing myeloma cells. Phase I of the trial aimed to determine the recommended Phase II dose (RP2D) of teclistamab and investigate the safety and tolerability of the drug at that dose. Patients in the trial were intolerant to established therapies, with a median of five prior lines of therapy having been received. The determined RP2D was 1500µg/kg, delivered subcutaneously. Dr van de Donk gives an overview of the patient population and talks through the safety and efficacy findings, concluding that teclistamab monotherapy has demonstrated promising results. The most common adverse effects at this dose were cytokine release syndrome and neutropenia. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.

Transcript (edited for clarity)

At this EHA meeting I gave an overview, an update, on the MAJESTIC-1 study where heavily pretreated patients received teclistamab as a monotherapy, and in this study, up till now patients were either treated intravenously, a total of 84 patients received intravenous teclistamab, or they received subcutaneous teclistamab, a total of 73 patients received subcutaneous administration at this moment...

At this EHA meeting I gave an overview, an update, on the MAJESTIC-1 study where heavily pretreated patients received teclistamab as a monotherapy, and in this study, up till now patients were either treated intravenously, a total of 84 patients received intravenous teclistamab, or they received subcutaneous teclistamab, a total of 73 patients received subcutaneous administration at this moment.

And we also have determined the recommended Phase II dose of teclistamab now. At the recommended Phase II dose 40 patients were treated. The recommended Phase II dose of teclistamab is 1500 micrograms of teclistamab given every week as a subcutaneous administration. This is preceded by two step of doses of 60 and 300 microgram per kilogram.

When we first look at the patient population, we can say that these patients were heavily pretreated. Approximately 80% of these patients were triple-class refractory and they have received a median of five prior lines of therapy. Then let’s look at the safety profile. We see some hematologic toxicity mainly during the first one or two cycles, and in the responding patients, the hematologic values substantially improved thereafter.

When it comes to non-hematologic adverse events, the most important, most common one is cytokine release syndrome, which is observed in approximately 60 to 70% of the patients, but this was never grade 3 or higher in the patients that received subcutaneous teclistamab and never led to treatment discontinuation.

The efficacy of teclistamab as a monotherapy is I think very promising because at the recommended Phase II dose, we observed a 65% overall response rate with a VGPR of 60% and a CR of a better rate of 40%. So, the response rate is not only very high, but also the depth of the response is very good. We have now a follow-up of seven months of the patients that received teclistamab at the recommended Phase II dose, and after this median follow-up of seven months, 85% of the responding patients were still on therapy and alive, and that suggests that the duration of the response will be a quite good one.

So, also here, I can conclude by saying that teclistamab as a monotherapy is a very promising BCMA-targeting bispecific antibody with a managing, with a manageable toxicity profile with low-grade cytokine release syndrome, which was always manageable in all the patients. And teclistamab as a monotherapy was inducing very promising activity with a 65% overall response rate with deep remissions in a majority of those responders and the responses were very durable and also deepened over time.

So, based on these responses and the safety profile in extensively pretreated patients, the promising beneficial, benefit/risk ratio, teclistamab will be evaluated in earlier phases of the disease, and also in combination with other agents, such as CD38 antibodies daratumumab and in combination with [inaudible].

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Disclosures

Niels van de Donk, MD, PhD, has received research support from Janssen Pharmaceuticals, AMGEN, Celgene, Novartis, and BMS; and serves in advisory boards for Janssen Pharmaceuticals, AMGEN, Celgene, BMS, Takeda, Roche, Novartis, Bayer, and Servier.

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