A first-in-human study of MB-CART2019.1, a tandem chimeric antigen receptor (CAR)-targeting CD20 and CD19, found no dose-limiting toxicities (DLT) and no severe grade 3 or worse cytokine release syndrome (CRS) or neurotoxicity in elderly patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Five patients in the study achieved compete response and had an ongoing response at data cutoff.
“There are 2 CAR T-cell [CAR-T] products — tisagenlecleucel and axi-cel — which are approved for use after failure of 2 prior lines of systemic treatment,” said Peter Borchmann, of University Hospital of Cologne, Germany, who presented results during the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. “However, about half of patients will not have benefit from this treatment [and will] show progressive disease or relapse, indicating a significant unmet medical need in this setting.”
The phase 1 study was conducted with a 6+3 design, with 2 predefined dose levels of the bispecific CAR-T construct MB-CART2019.1. Dose level 1 was 1.0 × 106 CAR T cells per kg body weight; dose level 2 was 2.5 × 106 per kg body weight.
The primary objective was to assess safety of the product by determining the maximum tolerated dose (MTD), defined as the highest dose level at which less than 33% of patients experienced DLT until day 28 after infusion.
Patients had CD20- and CD19-positive relapsed or refractory B-cell NHL without curative treatment options. The trial protocol was amended so that dose level 2 was only in second-line, non–transplant eligible diffuse large B-cell lymphoma (DLBCL). Six patients have been enrolled at each dose level.
There were no DLTs. Cytokine release syndrome of grade 3 or worse was not observed at either dose level, but CRS of any grade occurred in 58% of patients. There was also no neurotoxicity of grade 3 or worse. There was only 1 case of mild neurotoxicity at dose level 2. Infections were observed in both cohorts, however, there was no persisting neutropenia. Tocilizumab and dexamethasone were required in 1 patient each.
Seventy-five percent of patients responded to MB-CART2019.1. Five of 12 patients had a complete response. At dose level 1, the ORR was 50% and at dose level 2 the ORR was 100%. Of the 5 patients who achieved complete remission, responses are ongoing in all 5 participants up to 14 months at data cutoff.
Importantly, persistence of MB-CART2019.1 was observed in 12 out of 12 patients at data cutoff, Borchmann noted.
Based on these results, the recommended dose of MB-CART2019.1 is 2.5 × 106 per kg body weight.
Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.
Borchmann P, Juhling A, Godel P, et al. Phase I trial of MB-CART2019.1, a novel CD20 and CD19 targeting tandem chimeric antigen receptor, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. Presented at 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 404.
This article originally appeared on Cancer Therapy Advisor