The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

AUTO3, an investigational chimeric antigen receptor (CAR) T-cell (CAR-T) therapy with 2 independent CARs (targeting CD19 and CD22), given in combination with pembrolizumab, appears safe and effective in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to phase 1 data presented by Aravind Ramakrishnan, MD, of Sarah Cannon Research Institute, Nashville, Tennessee, at the ASCO20 Virtual Scientific Program.

“AUTO3 aims to address an unmet need in relapsed/refractory diffuse large B-cell lymphoma by targeting 2 escape mechanisms,” Dr Ramakrishnan said.  “Although currently available CD19 CAR T cells are highly active in relapsed lymphomas, durable CRs are only seen in 29%-37% of eligible patients.”

The Alexander study was designed to test if dual-targeting of CD19 and CD22 would reduce the probability of antigen escape. The study included patients with relapsed or refractory disease or transformed DLBCL who experienced relapse after at least 2 prior lines of therapy or autologous stem cell transplant. The median number of prior therapies was 3.


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Lymphodepletion was given with fludarabine and cyclophosphamide prior to AUTO3. Patients received escalating doses of AUTO3 alone, combined with 3 doses of pembrolizumab, or with a single dose of pembrolizumab.

The most commonly occurring adverse events of grade 3 or worse were hematologic events including neutropenia (87%), thrombocytopenia (57%), and anemia (48%). No dose-limiting toxicities were observed. There were no AUTO3-related deaths.

Grade 1 cytokine release syndrome (CRS) occurred in 26.1% of patients and grade 2 in 13% of patients. No grade 3 or worse CRS was observed. The median time to CRS was 7 days with a median duration of CRS of 5 days.

“In our experience this appears better than CRS rates seen with currently approved CD19 CAR T-cell products,” Dr Ramakrishnan said.

There was only 1 case of grade 3 neurotoxicity, which resolved quickly with steroids. No neurotoxicity of any grade was seen with AUTO3 plus pembrolizumab.

Clinical responses were seen in bulky tumors within as few as 28 days, and in the absence of severe CRS or neurotoxicity.

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The overall response rate for all dose levels was 65%, with a complete response rate of 48%. At doses greater than 150 x 106, the overall response rate improved to 69%, with a complete response rate of 56%. For patients at doses of 150 x 106 or greater combined with pembrolizumab, overall response rate was 75%, with a complete response rate of 63%.

Eleven of 23 enrolled patients have achieved a complete remission. All patients treated with pembrolizumab or treated with at least 150 x 106 are still in remission.

“This improved duration of response may be due to the dual targeting of CD19 and CD22 achieved with AUTO3 and the use of pembrolizumab to prevent early T-cell exhaustion,” Dr Ramakrishnan said.

Disclosure: The described study was funded by Autolus Therapeutics. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.

Reference

Osborne W, Marzolini, Tholouli E, et al. Phase I Alexander study of AUTO3, the first CD19/22 dual targeting CAR T cell therapy, with pembrolizumab in patients with relapsed/refractory (r/r) DLBCL. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 8001.