On June 4, 2019 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leading off-the-shelf, allogeneic T-cell immunotherapy company developing novel treatments for patients with cancer, autoimmune and viral diseases, reported that the Company’s collaborators at Memorial Sloan Kettering Cancer Center (MSK), Prasad S. Adusumilli, M.D. and Michel Sadelain, M.D., Ph.D., presented an update on encouraging results from an ongoing MSK investigator-sponsored Phase 1 clinical study (NCT02414269) of a mesothelin-targeted CAR T immunotherapy for patients with mesothelin-associated malignant pleural solid tumors, primarily mesothelioma, who progressed following platinum-containing chemotherapy (Press release, Atara Biotherapeutics, JUN 4, 2019, View Source [SID1234536855]). Mesothelin-targeted, autologous CAR T cells delivered regionally were well-tolerated and showed encouraging anti-tumor activity in combination with pembrolizumab, a PD-1 checkpoint inhibitor. The findings were presented today at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2019 in Chicago.

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"The updates to this study presented by our MSK collaborators reaffirm mesothelin as a promising target for patients with advanced mesothelioma and establishes an important proof-of-concept advancement for CAR T immunotherapy in solid tumors," said Christopher Haqq, M.D., Ph.D., Executive Vice President and Chief Scientific Officer of Atara Biotherapeutics. "Based on these continued encouraging safety results and anti-tumor responses, Atara recently prioritized our mesothelin-targeted CAR T program and anticipate autologous ATA2271 will be Atara’s first next-generation CAR T IND in advanced mesothelioma."

The MSK Phase 1 clinical study has recruited 27 patients, 25 with malignant pleural mesothelioma (MPM), one with metastatic lung cancer and one with metastatic breast cancer, who had a median of 3 prior treatment regimens, to evaluate the safety and potential anti-tumor activity of a CD28-costimulated, mesothelin-targeted autologous CAR T immunotherapy. The study added two higher dose cohorts to the six-dose cohorts reported in March 2019 with administration directly to the tumor site. Twenty-two of the 27 patients were subsequently treated with pembrolizumab, a PD-1 checkpoint inhibitor.

Mesothelin-targeted, autologous CAR T administration was found to be generally well tolerated, with no CAR T-related toxicities higher than grade 2 observed based on monitoring multiple clinical, radiological, and laboratory parameters.

In a subset of 16 MPM patients who also received lymphodepleting chemotherapy and at least 3 doses of pembrolizumab with a minimum follow-up of 3 months following the final dose of PD-1, the 12-month overall survival (OS) was 80% and best overall response rate (ORR) was 63% (10 of 16), consisting of 3 durable investigator-assessed complete responses (CR) and seven partial responses (PR). Eleven of the 16 patients in this subset were programmed cell death ligand 1 (PD-L1) negative, defined as undetectable expression of PD-L1 in tumor cells by immunohistochemistry, with 6 of the 10 total responses observed in PD-L1 negative patients (1 CR and 5 PR). CAR T cells persisted in the pleural fluid and trafficked to the peripheral blood in these 16 patients for up to 42 weeks.

Following progression on standard platinum-containing chemotherapy, the expected 12-month OS, median OS and ORR for patients with MPM treated with a PD-1 containing regimen is 63%, 11-18 months and 5%-29%, respectively.1-5

MSK is also investigating mesothelin-targeted CAR T cells for patients with mesothelin-associated advanced breast cancer (NCT02792114). Additional results from these ongoing studies are expected to be presented at upcoming scientific congresses.

Abstract 2511: Regional delivery of mesothelin-targeted CAR T cells for pleural cancers: Safety and preliminary efficacy in combination with anti-PD-1 agent
Oral Presentation Date and Time:Tuesday, June 4, 2019, 8:36 a.m. – 8:48 a.m. CDT
Session Title: The Who, What, and Where of CAR T
Location: S406, McCormick Place, South Building, Chicago, IL
Authors:Prasad S. Adusumilli, Marjorie G Zauderer, Valerie W Rusch, Roisin E O’Cearbhaill, Amy Zhu, Daniel Ngai, Erin McGee, Navin Chintala, John Messinger, Waseem Cheema, Elizabeth F Halton, Claudia R Diamonte, John Pineda, Alain Vincent, Shanu Modi, Steve Solomon, David R Jones, Renier J Brentjens, Isabelle C Riviere, Michel W Sadelain
Affiliations:Memorial Sloan Kettering Cancer Center