Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
Roisin Eilish O'Cearbhaill , Sacha Gnjatic , Carol Aghajanian , Alexia Iasonos , Jason A. Konner , Nicolle Losada , Debra Sarasohn , Teresa Rasalan , William P. Tew , Dmitriy Zamarin , Phillip Wong , Paul Sabbatini
Background: WT1 is highly expressed in serous ovarian cancer. GPS is WT1-targeting heteroclitic peptide tetravalent non-HLA-restricted vaccine, and has shown promising phase 2 activity in AML, mesothelioma and myeloma. Efficacy of GPS may be enhanced through checkpoint blockade, providing a rationale for combining it with anti-PD1 antibody, nivo. We conducted a phase I study to evaluate the safety and immunogenicity of the combination in WT1+ OC in remission. Methods: Pts with WT1+ OC in ≥2nd remission were enrolled from 06/16-07/2017, and received GPS (800 mcg) x 6 total doses mixed with adjuvant (0.5 ml) and 70 mcg GM-CSF (all s.c. in extremities) and nivo 3 mg/kg IV q2wks over 12 weeks. DLTs were assessed using CTCAE criteria, with detection of > 2/10 DLTs deeming the combination unsafe. Treatment was continued until disease progression or toxicity. Immune responses (IgG & IgM WT1 antibody, T cell assays) induced by the combination were evaluated. The 1-year progression-free survival (PFS) rate, defined as the interval from start of preceding chemo to date of progression or death, is an exploratory objective. Results: n=11; Median age 61 yrs (41-76). 7 pts in 2nd and 4 pts in 3rd remission. 1 DLT (gr 3 myositis with myocarditis post GPS and nivo #2). Most common AEs were Gr ≤2 fatigue and injection site reactions. Immune Response Results: n=9; Serum levels of antigen-specific IgG (against both individual WT1 peptides in GPS and the full-length WT1) significantly increased in 86% of evaluable pts between study wks 6-27. Antigen-specific T cell responses to individual WT1 peptides were observed between 6-15 wks, primarily CD4 and to a smaller extent, CD8 T cells. 1yr PFS rate was 64% in the ITT analysis (7/11) and 70% (7/10) in pts who had > 2 GPS/nivo doses. Conclusions: Administration of GPS in combination with nivo was safe, well tolerated and induced high frequency of T- and B-cell immune responses, warranting further evaluation. The 1yr PFS rate compares favorably to historic rates of approximately 50% in comparable populations. Additional cohorts are planned to receive the current combination along with vaccination against additional tumor-associated antigens. Clinical trial information: NCT02737787
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