ASCO 2021 | MajesTEC-1: update on RP2D of teclistamab in R/R myeloma
Amrita Krishnan, MD, City of Hope, Duarte, CA, shares an update on the Phase I MajesTEC-1 study (NCT03145181) of teclistamab, an IgG4 bispecific antibody which targets BCMA and CD3, in patients with relapsed/refractory myeloma. Dr Krishnan reports that teclistamab was well-tolerated with mild cytopenias and neurotoxicity and grade one or grade two cytokine release syndrome. The overall response rate among evaluable patients treated at the recommended Phase II dose (RP2D) (n=40) was 65%, with 58% achieving a very good partial response or better, and 30% achieving a complete response or better. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.
Transcript (edited for clarity)
Teclistamab is a BCMA CD3 bispecific T-cell engager. BCMA is highly expressed on myeloma cells and has limited expression on normal tissue, making it an ideal target for anti-myeloma strategies. MAJESTIC was a Phase I first-in-human study studying teclistamab in patients with relapsed/refractory myeloma. It identified the recommended Phase II dose, which was a weekly subcutaneous dosing of 1500 micrograms per kilo with step-up doses of 60 micrograms per kilo and 300 micrograms per kilo...
Teclistamab is a BCMA CD3 bispecific T-cell engager. BCMA is highly expressed on myeloma cells and has limited expression on normal tissue, making it an ideal target for anti-myeloma strategies. MAJESTIC was a Phase I first-in-human study studying teclistamab in patients with relapsed/refractory myeloma. It identified the recommended Phase II dose, which was a weekly subcutaneous dosing of 1500 micrograms per kilo with step-up doses of 60 micrograms per kilo and 300 micrograms per kilo.
The MAJESTIC trial was for patients who had relapsed disease. Of note, patients could not have had prior anti BCMA therapy. As I mentioned, the identified dose 1500 micrograms per kilos, subQ weekly. This was a group of heavily pretreated patients with a median of five prior lines of therapy. 36% of the recommended Phase II dose were penta-drug refractory, 83% were triple class refractory.
We found that teclistamab was well tolerated. Cytopenias were generally mild and confined to the step-up dosing into cycles one and cycle two. There was one episode of neurotoxicity, also mild grade one tremor in a patient and it resolved without any intervention. The injection site reactions also mild and treated with symptomatic therapies, such as topical steroids. We saw CRS in 70% of the patients and all CRS events were grade one and grade two. Median onset to CRS was two days and median duration of the CRS was also two days.
In this group of heavily pretreated patients, we found a very encouraging response rate. At the recommended Phase II dose, the response rate was 65% and also, we found that responses were deep, with 58% of patients achieving a VGPR and 40% achieving a complete response or better. Responses were also rapid. Median time to first response was one month. And in a subgroup of patients, we also found MRD-negative responses.
In regards to durability of responses, follow up is still relatively short, but the responses appear durable and to deepen over time. 85% of the responders after a median follow-up of 7.1 months are alive and continuing on therapy. We also have more data on the IV cohorts with longer follow-up and after a median follow-up of 15.6 months, 59% of the responders remain on therapy. The PK and PD data also support this dosing schedule and show high exposure at this level, as well as evidence of consistent T-cell activation. And this dose is now being evaluated in an open label Phase II expansion study.
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Disclosures
Amrita Krishnan, MD, has participated in consultancy work for GSK, Pfizer, Sanofi, BMS and Oncopeptides; and has participated in a speakers bureau with GSK, Amgen, BMS, Takeda and SAB Sutro.
