Autolus presented new data on AUTO1 in relapsed or refractory indolent B cell lymphomas

The results come from nine adults with relapsed or refractory low grade B-cell lymphoma despite high disease burden. All patients went into complete remission. No patients suffered grade 3 CRS, and only one participant had a grade 2 cytokine reaction. There were four cases of grade 1 CRS. It is still early days for the trial—the median duration of response is 3.1 months—and the sample size is small. The available data offer encouragement, though, with complete response rate and level of grade 3 CRS improving on the data generated during the development of Yescarta.

Allogene’s anti-CD19 CAR T shows durability within range of autologous competitors

Phase 1 data unveiled by Allogene suggest allogeneic CAR T cell therapies have the potential to match their autologous counterparts when it comes to durability of response, but more data are needed. Allogene’s readout keeps CD19-targeting ALLO-501 on par with marketed autologous therapies on efficacy, and gives it a leg up on safety with no reported cases of Grade 3 or Grade 4 cytokine release syndrome or graft-versus-host disease and one case of Grade 3 neurotoxicity.  Among 11 CAR T-naïve large B-cell lymphoma patients treated with ALLO-501, 36% maintained a CR at six months following a single infusion, putting it within the range of six-month durability demonstrated by autologous anti-CD19 CAR Ts. Among 21 follicular lymphoma patients, 24% had a CR at six months. The longest ongoing CR in the cohort is 15 months. Additionally, Allogene reported interim Phase I data from the Alpha-2 trial evaluating ALLO-501A, a next-generation version of ALLO-501 that is being prioritized for further development, that showed comparable efficacy and safety. The pivotal Phase 2 portion of Alpha-2 is slated to begin by year-end.

TCR cell therapies continue to gain traction with early Phase 2 readout from Adaptimmune

Adaptimmune’s initial pivotal readout for its MAGEA4-targeted TCR cell therapy adds to a trickle of positive data for cell therapies in solid tumors, where immunosuppressive micro-environments and a dearth of tumor-specific targets have been major barriers. Adaptimmune Therapeutics plc reported afamitresgene autoleucel (afami-cel) led to a 41% objective response rate, with 12 responses among 29 synovial sarcoma patients, in the Phase II SPEARHEAD-1 trial. Detailed data will be presented at ASCO. Data from the first 45-patient cohort of SPEARHEAD-1 will be used to support a BLA submission to FDA next year, which could put Adaptimmune on track to become the first company to bring this modality to the market.

FDA clears IND application for CD20-directed CAR-T to treat B-cell malignancies

FDA cleared an IND application for MB-106, a chimeric antigen receptor T-cell therapy designed to treat patients with relapsed or refractory, CD20-positive B-cell malignancies. The application includes indications for NHL and CLL. MB-106 from Mustang Bio is an autologous, gene-edited CAR T-cell therapy that targets the CD20 protein on the surface of cancer cells. The IND clearance will allow Mustang Bio to begin enrollment of a multicenter phase 1/phase 2 clinical trial that will evaluate the safety and efficacy of MB-106. The study is scheduled to start by the end of 2021. The FDA based the IND clearance on an interim analysis of an ongoing phase 1/phase 2 study at Fred Hutch that uses the same vector deployed to manufacture MB-106. Data from the study presented during last year’s ASH meeting showed an 89% ORR and 44% complete response rate among the first nine patients to receive the therapy for relapsed or refractory B-cell NHL. The therapy also exhibited a favorable safety profile: one patient had grade 3 cytokine release syndrome, but there were no reports of neurotoxicity.

REGULATORY

FDA grants Fast Track designation to novel CAR T-cell therapy for thyroid cancers

FDA has granted a Fast Track designation to the autologous CAR-T cell agent, AIC100, for the treatment of patients with anaplastic thyroid cancer and refractory poorly differentiated thyroid cancer. The agent is developed by AffyImmune Therapeutics and is currently under investigation in the Phase 1 study of patients with relapsed and/or refractory advanced thyroid cancer and ATC. Approximately 24 patients will be enrolled in the study.