Atara Biotherapeutics Announces Collaborator Presentation Updating Positive Phase 1 Clinical Results for a Mesothelin-Targeted CAR T Immunotherapy in Patients with Advanced Mesothelioma
In a subset of 16 malignant pleural mesothelioma patients with minimum follow-up time of 3 months who also received pembrolizumab and lymphodepleting chemotherapy, 12-month overall survival was 80% and best overall response rate was 63%, including 3 investigator-assessed complete responses
Clinical findings presentedat the
“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
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
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:
Session Title: The Who, What, and Where of CAR T
1Vogelzang NJ, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44.
2Maio M, et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017 Sep;18(9):1261-1273.
3Scherpereel A, et al. Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial. Lancet Oncol. 2019 Feb;20(2):239-253.
4Alley EW, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017 May;18(5):623-630.
5Hassan R, et al. Avelumab in patients with previously treated mesothelioma: Updated phase 1b results from the JAVELIN Solid Tumor trial. Abstract 166,
This press release contains or may imply "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. For example, forward-looking statements include statements regarding: mesothelin as a target for patients with advanced mesothelioma; the use of CAR T immunotherapy for solid tumors; and Atara’s priorities for its CAR T program and the related next-generation CAR T INDs. These forward-looking statements are subject to risks and uncertainties, including those discussed in
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Source: Atara Biotherapeutics, Inc.