Abstract 1191TiP
Background
The majority of newly diagnosed metastatic non-small cell lung cancer (mNSCLC) patients will receive chemotherapy with a single-agent PD1 inhibitor as initial therapy. Combination immunotherapy with PD1-CTLA4 inhibitors either alone or with chemotherapy represent competing alternative treatment strategies. However, there exists a limited understanding of the immunologic factors that predict for preferential response to combination immunotherapy versus chemo-immunotherapy and no definitive biomarkers exist to select patients preferentially for either strategy. We seek to develop a novel chemotherapy-sparing strategy utilizing nivolumab-ipilimumab combined with intense cfDNA monitoring as initial treatment in mNSCLC patients with rapid treatment-intensification with chemotherapy in the subset of patients with unfavorable cfDNA response.
Trial design
The ATLAS trial (NCT04966676) is a phase II biomarker-driven study of combination immunotherapy with cfDNA-based treatment intensification. Newly diagnosed mNSCLC patients (n=50 pts, PD-L1 expression <50%) are treated initially with nivolumab (360 mg IV q3weeks) and ipilimumab (1 mg/kg q6weeks). Patients undergo blood collection for cfDNA analysis at baseline and before each cycle of nivolumab. Detectable tumor cfDNA is assessed after 4 weeks of therapy and patients without a significant tumor cfDNA response will undergo treatment intensification with 2 cycles of platinum-doublet chemotherapy. 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. Serial tumor tissue will be evaluated using CITEseq as well as imaging mass cytometry (IMC) to evaluate the frequency, activation state and spatial relationships of key immune populations and their evolution in response to therapy. The deep characterization of the evolving tumor immune microenvironment will be utilized to define novel biomarkers response/resistance to ipilimumab-nivolumab.
Clinical trial identification
NCT04966676.
Editorial acknowledgement
Legal entity responsible for the study
University Health Network - Princess Margaret Cancer Centre.
Funding
Princess Margaret Cancer Foundation.
Disclosure
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. A. Sacher: Financial Interests, Institutional, Invited Speaker: Genentech-Roche, BMS, AstraZeneca, Amgen, Iovance, CRISPR Therapeutics, Merck, Pfizer, GSK, Spectrum, Lilly. All other authors have declared no conflicts of interest.