ASCO 2021 | Efficacy and safety of M-Pola for R/R B-cell NHL

The combination of mosunetuzumab plus polatuzumab was studied pre-clinically and there seemed to be synergy between these two drugs in B-NHL. So, this was a Phase I/II study, which was performed in patients with B-non-Hodgkin lymphoma in the relapse/refractory setting. The results which were presented at EHA were in the Phase I cohort with 22 patients. And this included primarily patients with aggressive B-cell lymphoma, such as diffuse large B-cell lymphoma, follicular lymphoma, grade IIIB or transformed lymphoma. There were three patients with follicular lymphoma grades I to IIIA as well, which were included in this study.

And this was a combination of the CD20, CD3 bispecific antibody mosunetuzumab with the CD79b ADC polatuzumab, and there was step-up dosing of the mosunetuzumab, which was done on day one, day eight and day 15 of cycle one, and then from cycle two onwards, it’s on day one. Polatuzumab was given for six cycles and mosunetuzumab was given for eight cycles for patients who achieved a complete remission, or for 17 cycles for patients who achieved partial remission or stable disease. So, the patient population who enrolled had significant refractory disease. There were 82% of patients were refractory to last line of prior therapy, and 91% of patients were refractory to their last anti-CD20 therapy, so, and also heavily pretreated, with median number of prior therapies being three.

You know, in this population, the safety was really as expected with the individual drugs. The most common side effects which were noted included, you know, neutropenia, which was there, as well as some neuropathy. So, for example, neutropenia was seen in about 55% of patients. Grade three neutropenia or higher was seen in 41% of patients and peripheral neuropathy was seen in 41% of patients with grade three or higher peripheral neuropathy in about 14% of patients.

Most importantly, the adverse events of special interest such as cytokine release syndrome and neurotoxicity were very low. Specifically, the cytokine release syndrome was seen in only two patients. So, just 9% of patients develop cytokine release syndrome, and these were all both grade one. So, there was no grade two or higher cytokine release syndrome, and these patients did not need tocilizumab, they did not need vasopressors, they did not need to get to the intensive care unit, and these were reversible. There was actually no incidents of ICANS, so no neurotoxicity, immune effector cell associated neurotoxicity events noted in the study, which was really excellent in terms of the safety standpoint.

Now, in terms of efficacy, the results were really fantastic in this heavily pretreated and refractory population of patients. The best overall response rate was 68.2% with a complete response rate of 54.5%. In aggressive non-Hodgkin lymphoma, the best overall response rate was 63.2% with a complete response rate of 47.4%. Importantly, the study also included patients who had failed CAR T-cell therapy. There were seven patients in this 22 patient cohort, which had failed CAR T-cell therapy, and complete response rate in that population was 28.6%, with the best overall response rate of 57.1%. And in follicular lymphoma grade 1 to 3A, the complete response rate was 100%.

So overall, you know, really fantastic efficacy results in this difficult to treat population. The most important part was that the complete responses appeared to be durable, and there were several patients who continue to be in a complete response well after stopping their treatment, as I mentioned, the four patients who had received a complete response, treatment stopped at eight cycles. And we have several patients who are in a remission more than a year after that, again, suggesting excellent depth as well as durability of response.