Abstract P2-14-17: A phase 1b study of PVX-410 vaccine in combination with pembrolizumab in metastatic triple negative breast cancer (mTNBC)
Authors: Isakoff Steven J , Tung Nadine M. , Yin Jun , Tayob Nabihah , Parker Joanne , Rosenberg Julie , Bardia Aditya , Spring Laura , Park Hannah , Collins Maya , Barry William T. , Severgnini Mariano , Peterkin Doris , Tolaney Sara M. 
Published: March 2022

Abstract
Background: Immunotherapy with checkpoint inhibition is active in mTNBC. Both pembrolizumab and atezolizumab are FDA approved for programmed cell death ligand 1 positive (PDL1+) mTNBC. Vaccines may further induce host immune response and enhance therapeutic activity of checkpoint inhibitors. PVX-410 (PVX) (OncoPep, Inc.) is a novel, HLA-A2 restricted, tetra-peptide vaccine, with 3 of its 4 antigens (XBP1[2 splice variants] and CD138) commonly overexpressed in TNBC. We present results from a phase 1b study evaluating the immune response, safety and tolerability, and clinical activity of PVX and pembrolizumab (PEM) in mTNBC. Methods: Eligibility for this phase 1b multi-center, single-arm study included HLA-A2+, PD-L1 unselected female patients (pts) ≥18 years with metastatic or inoperable locally advanced TNBC, measurable disease, and any number of prior therapies, including prior checkpoint inhibitor therapy. Pts received 6 doses of 800µg PVX emulsified in Montanide ISA 720 VG by subcutaneous injection co-administered with intramuscular Hiltonol weekly for 6 weeks (wks) followed by booster vaccine doses at wks 10 and 28, with concurrent intravenous 200 mg PEM every 3 wks starting with the second PVX dose. Therapy was given until progressive disease, unacceptable toxicity or a maximum of 24 months. Blood samples were scheduled for immune response assessment at baseline and at weeks 2, 5, 10, 28, and 52 post-treatment initiation. The primary objective was PVX- specific immune response at week 10. Immune response was defined as a ≥2-fold change over baseline in the proportion of CD3+CD8+ T cells that expressed IFNγ and the proportion of CD3+CD8+ T cells positive for PVX tetramers following an in vitro stimulation of PBMC with PVX peptides using a flow cytometric assay. Secondary objectives were immune response at wk 28, safety and tolerability, and clinical endpoints (RR, CBR, DCR, DoR, PFS, and OS). Results: Between 3/2018 and 8/2020, 19 pts enrolled. Median age was 62 yrs (range 46-79), with median 2 (range 0-9) lines of prior therapy for metastatic disease. Median disease-free interval among 16 pts with prior early TNBC was 3.3 years. Among 19 enrolled patients, 16 were available for analysis at the time of abstract submission. Among the 16, 10 pts were evaluable at week 10 and 7(70%) demonstrated a PVX specific immune response. There were 6 patients who progressed before week 10, of whom 3 (50%) had a positive immune response at the EOT visit. Immune response persisted in all evaluable pts assessed at week 28 (n=4). Immune response data for all evaluable patients will be updated at the presentation. Among 19 patients evaluable for safety analysis, the most common adverse events (AEs) attributable to PVX (grade ≥2) included: fatigue (21%), arthralgia (11%) injection site reaction (5 %) pain (5%) lymphocyte count decreased (5%), maculopapular rash (5%) and skin infection (5%) . There were two grade 3 AEs attributed to PEM (AST elevation, hyponatremia) and one grade 4 AE (ALT elevation). There were no grade 5 AEs. The clinical benefit rate (CR+PR+SD for ≥16 weeks) was 31.6% with no confirmed partial or complete responses. Best overall response was SD in 9 (47%) patients. Analysis of additional clinical endpoints including PFS and OS is ongoing and will be presented at the meeting. Conclusions: PVX plus PEM is safe with manageable toxicity in pts with mTNBC. No new unexpected adverse events were identified. Immune response data show PVX induces antigen-specific T cell expansion as observed by increases in PVX tetramer and IFN positive T cells. Clinical disease control was observed with a CBR of 31.6%. Based on these promising immune response results in this pretreated population, a phase 2 study with PVX+PEM in combination with standard chemotherapy in treatment naïve, PD-L1+ mTNBC is underway (NCT04634747).
Citation Format: Steven J Isakoff, Nadine M. Tung, Jun Yin, Nabihah Tayob, Joanne Parker, Julie Rosenberg, Aditya Bardia, Laura Spring, Hannah Park, Maya Collins, William T. Barry, Mariano Severgnini, Doris Peterkin, Sara M. Tolaney. A phase 1b study of PVX-410 vaccine in combination with pembrolizumab in metastatic triple negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-17.