385P - A phase II study of nivolumab, ipilimumab plus bicalutamide in metastatic breast cancer

Background

The androgen receptor (AR) antagonist, bicalutamide, is well tolerated and is associated with best response of stable disease (TBCRC-011) in the treatment of AR+ metastatic breast cancer (MBC). In preclinical models, AR antagonists may modulate T-cell activity and stimulate thymic generation of naïve T-cells. Here we report long-term outcomes and T-cell effects from a phase II trial of bicalutamide (150mg oral daily) combined with immune checkpoint blockade (ICI, nivolumab 240mg IV q2w & ipilimumab 1mg/kg IV q6w).

Methods

This is a Simon 2-stage trial for 1st/2nd line AR+ triple-negative MBC (TNBC, n=15) or hormone positive (HR+) MBC (n=14), with 1° endpoint of iRECIST 24wk clinical benefit rate (CBR); 2° endpoints of survival and safety; and exploratory endpoint of treatment-associated thymic T-cell generation (measured by Mayo Laboratories T-cell receptor excision circle [TREC] assay & blood flow cytometry).

Results

Outcomes are summarized in the Table. Two patients have durable partial response (PR) in the TNBC cohort at 204+ and 72+ weeks: the first patient (PDL1 CPS 3%, AR 2%) discontinued all therapy after cycle 2 (grade 3 colitis); whereas the second (CPS 0%, AR 100%) remains on treatment, achieving PR after 72wk. Toxicity is consistent with the known profile for ICIs. Therapy was associated with CD8+ expansion (23/mcl/month, p=0.03), whereas TREC expansions were restricted to a subset of younger patients (

Conclusions

Durable clinical benefit was observed in a subset of AR+ TNBCs, however 24-week CBR did not exceed the Simon futility boundary for trial expansion in either arm. Further research is needed to identify predictive biomarkers of response and to understand the impact of AR antagonists on T-cells.

Clinical trial identification

NCT03650894 Trial opening/release date: 4/3/2019.

Editorial acknowledgement

Legal entity responsible for the study

Providence Health and Services.

Funding

Bristol-Myers Squibb, Bristol-Myers Squibb II-ON.

Disclosure

D.B. Page: Other, Personal, Advisory Board: Genentech, Merck, Novartis, Lilly, Sanford Burnham Prebys, NGM Biopharmaceuticals, Sanofi, AstraZeneca; Other, Personal, Speaker’s Bureau: Genentech, OncoCyte, Novartis; Other, Personal, Research Funding: Merck, Brooklyn ImmunoTherapeutics, Bristol-Myers Squibb. A.K. Conlin: Other, Advisory Board: Seattle Genetics/Astellas, AstraZeneca, Gilead Sciences; Other, Travel, Accommodations, Expenses: Seattle Genetics/Astellas. S. Stanton: Other, Research Funding: Veanna; Other, Speaker, Consultant, Advisor: Margenza. T.A. Traina: Other, Advisory Role: Aduro Biotech; Other, Advisory Board: Advaxis, AstraZeneca, Athenex, Bristol-Myers Squibb, Eisai, Daiichi Sankyo, Genentech/Roche, Genomic Health, Halozyme, Immunomedics, Innocrin Pharma, Ionis Pharmaceuticals, Merck, Pfizer, Puma Biotechnology, Seagen; Other, Research Funding: AstraZeneca (Inst), Astellas Pharma, Carrick Pharm, Daiichi Sankyo, Eisai, Genentech/Roche, Immunomedics, Innocrin Pharma, Novartis, Pfizer. A. Gucalp: Other, Research Funding: Pfizer, Innocrin Pharmaceuticals, BioAtla, Bristol-Myers Squibb, Merck, Novartis, OncoTherapy Science, Roche, Zenith Epigenetics. All other authors have declared no conflicts of interest.