Roy S. Herbst, MD, PhD

3089Background: In Study JVDF (NCT02443324), we combined ramucirumab (VEGFR2 antagonist) and pembrolizumab (PD-1 antagonist) to simultaneously target the tumor microenvironment and immune checkpoints in patients with advanced non-small cell lung cancer (NSCLC), gastric or gastroesophageal junction adenocarcinoma (G/GEJ), urothelial carcinoma (UC) or biliary tract cancer (BTC). We reported that this combination was associated with increased antitumor activity in patients with PD-L1 positive tumors by immunohistochemistry (IHC) compared with PD-L1 negative tumors.1) Here we explore the association between baseline gene expression profiles and clinical outcomes. Methods: JVDF was a nonrandomized phase 1a/b trial that treated patients with intravenous ramucirumab at 8 mg/kg on days 1 and 8 (G/GEJ, BTC) or 10 mg/kg on day 1 (G/GEJ, NSCLC, UC) plus pembrolizumab (200 mg day 1 …

IntroductionThe objective of the Lung-MAP sub-study S1400A was to evaluate the response rate to durvalumab, an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with squamous non–small-cell lung cancer (SqNSCLC).Patients and MethodsPatients who progressed on at least 1 prior platinum-based chemotherapy were eligible. The study was designed as a phase II/III trial comparing durvalumab with docetaxel but was modified to a single-arm, phase II trial with the primary endpoint of objective response when immunotherapy became an approved treatment.ResultsA total of 116 patients were registered to this sub-study; 78 to durvalumab and 38 to docetaxel. Of the 78 patients, 9 were ineligible, and 1 was not evaluable for endpoints. Responses were achieved in 11 patients among the 68 eligible and evaluable patients on durvalumab (overall response rate, 16%; 95% confidence interval [CI], 7 …

e21623Background: IMpower110 evaluated atezo mono in PD-L1–selected, chemo-naive patients (pts) with nonsquamous (nsq) or squamous (sq) NSCLC. At the interim analysis, IMpower110 met its primary OS endpoint, with a statistically significant and clinically meaningful improvement for atezo vs chemo in TC3 or IC3 wild-type (EGFR/ALK-negative) pts. We report on the safety profile of atezo vs chemo in IMpower110. Methods: 572 pts with stage IV nsq or sq NSCLC, PD-L1 expression ≥ 1% on TC or IC and ECOG PS 0-1 were randomized 1:1 to receive atezo (1200 mg IV q3w) or chemo (4 or 6 21-day cycles). In the chemo arm, nsq pts received cisplatin (cis) 75 mg/m2 or carboplatin (carbo) AUC 6 + pemetrexed (pem) 500 mg/m2 IV q3w; sq pts received cis 75 mg/m2 + gemcitabine (gem) 1250 mg/m2 or carbo AUC 5 + gem 1000 mg/m2 IV q3w. Safety was assessed in all treated pts (safety evaluable [SE …

Background: Cancer incidence rates in Connecticut are well above the national average with the greatest burden on African Americans, Hispanic/Latinos, and those with low socioeconomic status. In 2018, we launched the Yale Cancer Center’s (YCC) Cancer Disparities Firewall Project with the goal of providing a protective firewall around our catchment’s at-risk populations, specifically targeting breast, prostate, lung, and colorectal cancer. Methods: The Aims of the Cancer Disparities Firewall Project are to: 1) expand community outreach & education; 2) establish a “health” navigation program; 3) create infrastructure to support sustainable change. Strategies to accomplish Aims 1 & 2 require our presence in communities, workplaces, and other venues that are not always associated with health care institutions. Focusing on 2 key components of the cancer control continuum, prevention and early detection, and …

Introduction.VISTA/PD-1H is an Ig domain-containing type I transmembrane protein able to suppress T-cell activation and is being evaluated as a candidate anti-cancer immunotherapy target. VISTA can bind P-selectin glycoprotein ligand-1 (PSGL1) and V-set and immunoglobulin domain containing 3 (VSIG3) suggesting these interactions could mediate VISTA's immunomodulatory effect. We studied the tissue distribution of VISTA, PSGL1 and VSIG3 in human non-small cell lung cancer (NSCLC).MethodsWe used multiplexed quantitative immunofluorescence (QIF) to simultaneously measure DAPI, cytokeratin (CK), VISTA, PSGL1 and VSIG3 in 48 paired tumor/normal lung samples and in 850 stage I-IV NSCLCs from four independent cohorts represented in tissue microarray format. The first 2 NSCLC cohorts (Cohorts #1, n=382 and #2, n=282) included cases treated with standard of care non-immunotherapy …

Background The efficacy and safety of the anti–programmed death ligand 1 (PD-L1) monoclonal antibody atezolizumab, as compared with those of platinum-based chemotherapy, as first-line treatment for patients with metastatic non–small-cell lung cancer (NSCLC) with PD-L1 expression are not known. Methods We conducted a randomized, open-label, phase 3 trial involving patients with metastatic nonsquamous or squamous NSCLC who had not previously received chemotherapy and who had PD-L1 expression on at least 1% of tumor cells or at least 1% of tumor-infiltrating immune cells as assessed by the SP142 immunohistochemical assay. Patients were assigned in a 1:1 ratio to receive atezolizumab or chemotherapy. Overall survival (primary end point) was tested hierarchically according to PD-L1 expression status among patients in the intention-to-treat population whose tumors were wild-type with …

Osimertinib as adjuvant therapy in patients with stage IB–IIIA EGFR mutation positive NSCLC after complete tumor resection: AD Page 1 Osimertinib as adjuvant therapy in patients with stage IB–IIIA EGFR mutation positive NSCLC after complete tumor resection: ADAURA Roy S. Herbst1, Masahiro Tsuboi2, Thomas John3, Christian Grohe4, Margarita Majem5, Jonathan W. Goldman6, Sang-We Kim7, Dominika Marmol8, Yuri Rukazenkov8, Yi-Long Wu9 1 Roy S. Herbst 1 Medical Oncology, Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA; 2 Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Kashiwa, Japan; 3 Department of Medical Oncology, Austin Health, Melbourne, Australia; 4 Klinik für Pneumologie - Evangelische Lungenklinik Berlin Buch, Berlin, Germany; 5 Medical Oncology Services, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 6 David …

Purpose Programmed death ligand 1 (PD-L1) is expressed in tumor cells and immune cells, and both have been associated with response to anti-PD-1 axis immunotherapy. Here, we examine the expression of PD-L1 to determine which cell type carries the predictive value of the test. Experimental Design We measured the expression of PD-L1 in multiple immune cells with two platforms and confocal microscopy on three retrospective Yale NSCLC cohorts (425 nonimmunotherapy-treated cases and 62 pembrolizumab/nivolumab/atezolizumab-treated cases). The PD-L1 level was selectively measured in different immune cell subsets using two multiplexed quantitative immunofluorescence panels, including CD56 for natural killer cells, CD68 for macrophages, and CD8 for cytotoxic T cells. Results PD-L1 was significantly higher in macrophages in both tumor …