Initial results from a phase II study of nivolumab (NIVO) plus ipilimumab (IPI) for the treatment of metastatic castration-resistant prostate cancer (mCRPC; CheckMate 650).

Authors

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Padmanee Sharma

University of Texas MD Anderson Cancer Center, Houston, TX

Padmanee Sharma , Russell Kent Pachynski , Vivek Narayan , Aude Flechon , Gwenaelle Gravis , Matt D. Galsky , Hakim Mahammedi , Akash Patnaik , Sumit Kumar Subudhi , Marika Ciprotti , Tao Duan , Abdel Saci , Sarah Hu , G. Celine Han , Karim Fizazi

Organizations

University of Texas MD Anderson Cancer Center, Houston, TX, Washington University School of Medicine, St. Louis, MO, Penn Medicine Abramson Cancer Center, Philadelphia, PA, Centre Léon Bérard, Lyon, France, Medical Oncology, Institut Paoli-Calmettes, Marseille, France, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, Centre Jean Perrin, Clermont-Ferrand, France, University of Chicago Comprehensive Cancer Center, Chicago, IL, Bristol-Myers Squibb, Princeton, NJ, Gustave Roussy, Villejuif, France

Research Funding

Pharmaceutical/Biotech Company

Background: Immune checkpoint inhibitor monotherapy has shown limited clinical benefit in patients (pts) with prostate cancer, likely due to an immunologically “cold” tumor microenvironment. We report preplanned interim efficacy/safety for NIVO + IPI in pts with mCRPC from CheckMate 650. Methods: Asymptomatic/minimally symptomatic pts who progressed after 2nd-generation hormone therapy and have not received chemotherapy for mCRPC (cohort 1) and pts who progressed after taxane-based chemotherapy (cohort 2) were included. Treatment was NIVO 1 mg/kg + IPI 3 mg/kg Q3W for 4 doses, then NIVO 480 mg every 4 weeks. Coprimary endpoints: objective response rate (ORR) and radiographic PFS per PCWG2. Safety is a secondary endpoint. Exploratory endpoints include correlation of biomarkers with efficacy. Results: 78 pts had a minimum follow-up of 6 months; among pts with baseline measurable disease, ORR was 26% and 10% in cohorts 1 and 2 (Table). In both cohorts, ORR was higher in pts with PD-L1 ≥1%, DNA damage repair (DDR), homologous recombination deficiency (HRD), or above-median tumor mutational burden (TMB). Of all PSA responding pts (Table), 4 had PSA <0.2 ng/mL. Grade 3–4 treatment-related adverse events occurred in 39% and 51% of pts in cohorts 1 and 2; one grade 5 event occurred in each cohort. Conclusions: In a malignancy where immune checkpoint inhibitor monotherapy has previously shown limited success, NIVO + IPI demonstrated activity in pretreated pts with mCRPC, particularly in a biomarker-enriched population, with a safety profile consistent with this dosing schedule. Further study is warranted. Clinical trial information: NCT02985957

Cohort 1Cohort 2
ORR % (95% CI), n/Na26 (10–48), 6/2310 (2–27), 3/30
PD-L1b≥1%2/4 (50)2/8 (25)
<1%4/23 (17)0/20 (0)
DDRb+2/5 (40)2/5 (40)
4/14 (29)1/9 (11)
HRDb+2/3 (67)1/2 (50)
4/16 (25)2/12 (17)
TMBb,cHigh6/10 (60)3/6 (50)
Low0/9 (0)0/8 (0)
PSA responsed6/28 (21)5/40 (13)

n/N (%) unless noted aIn pts with baseline measurable disease

bIn pts with quantifiable tissue

cHigh/low TMB = above/below median (74.5 mutations/pt)

dConfirmed/unconfirmed PSA decline ≥50% from baseline in pts with baseline and ≥1 postbaseline PSA result

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Abstract Details

Meeting

2019 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer,Prostate Cancer

Sub Track

Prostate Cancer - Advanced Disease

Clinical Trial Registration Number

NCT02985957

Citation

J Clin Oncol 37, 2019 (suppl 7S; abstr 142)

DOI

10.1200/JCO.2019.37.7_suppl.142

Abstract #

142

Poster Bd #

A6

Abstract Disclosures