Abstract 2673: Association of PD-L1 combined positive score and immune gene signatures with efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients with metastatic gastroesophageal cancer (mGEC)
Authors: Ming Lei, Nathan Siemers, Dimple Pandya, Han Chang, Teresa Sanchez, Cecile Dorange, Christopher Harbison, Peter M. Szabo, Yelena Janjigian, Patrick A. Ott, Padmanee Sharma, Johanna Bendell, Jeffry Evans, Filippo de Braud, Ian Chau, Zachary Boyd
Journal: Cancer Research (2019)

Abstract Background: In the CheckMate 032 phase 1/2 study, NIVO ± IPI demonstrated clinically meaningful antitumor activity in patients with chemotherapy-refractory mGEC. Archival or fresh tumor biopsies were analyzed to determine whether expression of PD-L1 and selected immune gene signatures were predictive of response to NIVO ± IPI. Methods: Pooled analyses included all treatment regimens (NIVO 3 mg/kg, NIVO 1 mg/kg + IPI 3 mg/kg, NIVO 3 mg/kg + IPI 1 mg/kg, and patients treated with NIVO 1 mg/kg + IPI 1 mg/kg in the dose-escalation phase). PD-L1 immunohistochemistry (IHC; Dako PD-L1 IHC 28-8 pharmDx assay) was used to evaluate tumor PD-L1 expression, referred to as tumor proportion score (TPS). Combined positive score (CPS) was determined by evaluating PD-L1 expression on previously stained IHC slides using the CPS algorithm. Gene expression profiling (GEP) by RNA sequencing was used to evaluate immune cell activation and infiltration signatures, a Bristol-Myers Squibb (BMS) inflammatory signature, and PD-L1 gene expression. Results: The pooled CPS (N = 104), TPS (N = 130), and GEP (N = 40) cohorts were mostly representative of the overall CheckMate 032 mGEC cohort (N =163). At a median (range) follow-up of 23.4 (17.0-35.4) months, CPS at higher cutoffs correlated better with efficacy and had higher prevalence than TPS in all analyses (Table). For all immune gene signatures examined, responders had higher signature scores in aggregate. For the BMS inflammatory signature, the association between signature score and response was significant (P = 0.004; false discovery rate = 0.037). Conclusions: CPS demonstrated stronger association with efficacy of NIVO ± IPI than TPS in mGEC. Prevalence of CPS was higher than that of TPS. Among immune gene signatures examined, the BMS inflammatory signature achieved the best association with efficacy and warrants further investigation. All treatments combinedMethodNCutoffResponse rate, %Prevalence, %All patients163NA9.8100CPS1041026.533519.250114.168TPS130109.1857.710117.531NIVO 1 mg/kg + IPI 3 mg/kgMethodNCutoffResponse rate, %Prevalence, %All patients49NA20.4100CPS331054.533541.252128.076TPS421002502140.024CPS = combined positive score (number of PD-L1-staining tumor cells, lymphocytes, and macrophages relative to all viable tumor cells x 100); IPI = ipilimumab; NA, not applicable; NIVO = nivolumab; TPS = tumor proportion score Citation Format: Ming Lei, Nathan Siemers, Dimple Pandya, Han Chang, Teresa Sanchez, Cecile Dorange, Christopher Harbison, Peter M. Szabo, Yelena Janjigian, Patrick A. Ott, Padmanee Sharma, Johanna Bendell, Jeffry Evans, Filippo de Braud, Ian Chau, Zachary Boyd. Association of PD-L1 combined positive score and immune gene signatures with efficacy of nivolumab (NIVO) ± ipilimumab (IPI) in patients with metastatic gastroesophageal cancer (mGEC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2673.