A phase I study of concomitant galinpepimut-s (GPS) in combination with nivolumab (nivo) in patients (pts) with WT1+ ovarian cancer (OC) in second or third remission.

Authors

null

Roisin Eilish O'Cearbhaill

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

Organizations

Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, Icahn School of Medicine at Mount Sinai, New York, NY, Memorial Sloan Kettering Cancer Center, New York, NY

Research Funding

NIH

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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Abstract Details

Meeting

2018 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Clinical Trial Registration Number

NCT02737787

Citation

J Clin Oncol 36, 2018 (suppl; abstr 5553)

DOI

10.1200/JCO.2018.36.15_suppl.5553

Abstract #

5553

Poster Bd #

280

Abstract Disclosures