Abstract 1202TiP
Background
Hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) constitute leading global causes of cancer-related death. PD-1/PD-L1 inhibitor monotherapy exhibits poor efficacy in advanced HCC and NSCLC with liver metastases. Emerging data suggests that advanced HCC and NSCLC with liver metastases may be uniquely sensitive to combination therapy with atezolizumab-bevacizumab. The liver microenvironment possesses unique immunologic characteristics that may underpin this responsiveness but are presently poorly characterized. The study of the evolution of the liver tumor immune microenvironment in HCC and NSCLC with liver metastases following treatment with atezolizumab-bevacizumab represents a unique opportunity to elucidate the key immunologic mechanisms that underpin the aforementioned patterns of response/resistance. The INTEGRATE trial (NCT04563338) is an ongoing imCORE network investigator-initiated phase II study evaluating the response of both advanced HCC and NSCLC with liver metastases to treatment with atezolizumab +/- bevacizumab.
Trial design
Unresectable HCC (12 patients) and NSCLC with liver metastases (24 patients) are presently being recruited to a phase II study of atezolizumab +/- bevacizumab. HCC patients (Arm A) will be treated with atezolizumab-bevacizumab only. NSCLC patients with liver metastases will be randomized to receive either atezolizumab-bevacizumab (Arm B) or atezolizumab alone (Arm C). Radiographic response will be assessed as per RECIST v1.1 and progression-free survival (PFS) will be the primary study endpoint. Patients will undergo pre-treatment, on-treatment (3-4 weeks) and post-progression biopsies of both liver metastases and adjacent normal liver. Serial microbiome and blood collections will be performed. Deep immune profiling will be performed on serial tumor biopsies using CITE-seq and IMC. This approach has significant potential to identify novel immune cell subsets and interactions that underpin both resistance to PD-L1 monotherapy and sensitivity to PD-L1/VEGF combination therapy.
Clinical trial identification
NCT04563338.
Editorial acknowledgement
Legal entity responsible for the study
University Health Network - Princess Margaret Cancer Centre.
Funding
imCORE.
Disclosure
A. Sacher: Financial Interests, Institutional, Invited Speaker: Genentech-Roche, BMS, AstraZeneca, Amgen, Iovance, CRISPR Therapeutics, Merck, Pfizer, GSK, Spectrum, Lilly. S. Lau: Financial Interests, Personal, Other, Honoraria: AstraZeneca. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Lilly, MSD, Pfizer, Roche, Takeda. R. Garonce-Hediger: Financial Interests, Personal, Other, Employee: Roche-Genentech. J. Knox: Financial Interests, Personal, Advisory Board, advisor on HB portfolio and trials: AstraZeneca; Non-Financial Interests, Principal Investigator, Emerald 2. (not compensated): AstraZeneca; Non-Financial Interests, Principal Investigator, Nutide trial: Nucana. All other authors have declared no conflicts of interest.