Virtual Library

Start Your Search

M.I. Ahmad



Author of

  • +

    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
    • +

      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): M.I. Ahmad

      • Abstract
      • Slides

      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.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.