Teclistamab is a humanised B-cell maturation antigen CD3 bispecific antibody and I’m reporting on the first in human phase I clinical trial in relapsed refractory multiple myeloma. As we all know, patients who have relapsed refractory multiple myeloma, especially after having seen a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody, it’s poor. The median overall survival has been reported at anywhere between 6-11 months at best. So new therapies are required for this patient population and having a bispecific antibody strategy that targets BCMA would be a good off-the-shelf approach for an immune mediated therapeutic strategy.
Teclistamab is based off of the Janssen dual body antibody platform. In preclinical studies it has shown to not only be effective in killing myeloma cell lines but also primary myeloma cells from a heavily pre-treated patient population. I’m reporting on the dose escalation portion of the study where dosing was done from the start of cohort 1 at 0.3μg/kg all the way up to 720μg/kg. A total of 78 patients were treated on the study with a median time from diagnosis of about seven years, about six prior lines of treatment. 80% of the patients were triple class refractory, 41% of the patients were penta-drug refractory, 87% were refractory to an anti-CD38 monoclonal antibody and 86% were actually refractory to the prior line of treatment that was given.
In terms of safety the key feature to note was the fact that 56% of the patients had cytokine release syndrome but it was all grade 1 and 2 and this is across all the different cohorts. We only observed six neurotoxic events and of those four were grade 1 or 2. Two DLTs were observed, one was a grade 4 delirium and one was a grade 4 thrombocytopenia. 65% of patients did have infections but 21% of them were grade 3 or higher. Looking at the onset of CRS, it was about one day duration, it was also about one day. 54% of the patients received some supportive measure for the cytokine release syndrome.
What’s important to note is that the overall response rate which was available for cohorts up to the 270μg/kg dose saw an overall response rate of 67% for that particular cohort of twelve patients. We saw three CRs and three VGPRs in that group. Of the eight responders, seven were triple class refractory, five were penta-drug refractory and of those patients who were MRD evaluable four out of five were MRD negative at 10-6. Two patients had MRD negative CRs as well. Of the two patients who actually had serial MRD evaluations done they were sustained MRD negative at the five month and fourteen month mark respectively. The responses continued to deepen over time in this particular study.
We did not have the data mature to report for the 720μg/kg dose but we are hoping that we can do that in a subsequent congress.
So across the board, to conclude, we found that teclistamab had a safe profile manageable across all doses. The overall response rate of 67% with 50% having VGPR or higher was seen at the 270μg/kg dose in a highly refractory patient population. The dose escalation and expansion phases of the study are ongoing.
Why is it important to have these different treatment options for multiple myeloma?
We continue to make myeloma a chronically managed disease. As patients become refractory to available drug classes we need new drug classes and targets that will help improve the survival outcome of our patients.
