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N. Sulai
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-010 - Phase II Study of the Anti-PD-1 Antibody Pembrolizumab in Patients with Malignant Mesothelioma (ID 3020)
09:30 - 09:30 | Author(s): N. Sulai
- Abstract
Background:
Mesothelioma is a frequently "inflamed" tumor. We previously identified PD-L1 expression, a CD8 infiltrative pattern, and the presence of PD-1/PD-L1 immune checkpoints in about 1/3 of mesothelioma tumors, similar to the phenotype found in malignancies such as melanoma that benefit from immune checkpoint blockade (Kindler and Seiwert, ASCO 2014). Based on these data, we have initiated a single-center phase II trial (NCT02399371) of the anti-PD-1 antibody pembrolizumab in previously-treated mesothelioma patients. The rationale for this study is further supported by recent data from a phase IB multi-cohort study of pembrolizumab in PD-L1 positive solid tumors, in which an objective response rate of 28% and a disease control rate of 76% was observed in 25 pleural mesothelioma patients, who received 10 mg/kg pembrolizumab every 2 weeks (Alley, AACR 2015).
Methods:
Eligible patients have histologically-confirmed pleural or peritoneal mesothelioma, measurable disease, PS 0-1, disease progression on or after treatment with pemetrexed plus cis- or carboplatin, no more than 2 prior lines of cytotoxic therapy, normal organ function, and tissue available for correlative studies. Patients receive a flat dose of 200 mg pembrolizumab intravenously every 3 weeks. CT scans are obtained every 9 weeks. The primary objectives are: 1) to determine the objective response rate in A] an unselected population and in B] a PD-L1 positive population, and 2) to determine the optimal threshold for PD-L1 expression using the 22C3 antibody-based IHC assay. Secondary objectives include progression-free and overall survival, disease control rate, and toxicity. Correlative studies are intended to characterize the T-cell inflamed phenotype in mesothelioma via CD8, CD4, and PD-L1 staining, immune related gene expression signatures (Nanostring), and determination of other immune escape mechanisms including T-regulatory cells (FOXP3 expression), IDO expression, MDSCs, and other checkpoints/co-stimulatory signals by immunohistochemistry and/or flow cytometry. A single-stage binomial design will be used. Part A requires ≥ 3 responses in 35 patients. Part B, which uses PD-L1 pre-selection (optimal expression pattern and threshold determined in cohort A), requires ≥ 6 responses in 30 patients. Funded in part by a grant from the Mesothelioma Applied Research Foundation.
Results:
Not applicable.
Conclusion:
Not applicable.
