BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the NSCLC cohort.

8563 Background: Patient selection, dosing regimens and resistance mechanisms for immune checkpoint inhibitor combination therapy remain unmet medical needs in lung cancer. We present interim data from the small-cell lung cancer (SCLC) cohort of the ongoing BIOLUMA trial which evaluates efficacy and safety of nivolumab and ipilimumab in lung cancer with a broad translational program to identify potential biomarkers predictive of response and/or resistance including whole exome sequencing (WES) of serial biopsies, functional analysis of peripheral T-cells and gut microbiome analyses. Methods: BIOLUMA is an investigator initiated, multicentre non-randomised phase II trial in 2nd line patients with SCLC. The initial all-comer SCLC cohort was recently amended for inclusion of patients with high tumor mutation burden (TMB) only. Patients are pre-screened for TMB by WES at the time of first diagnosis. After progression on platinum-based therapy, 4 cycles of nivolumab 1 mg/kg q3w in combination with ipilimumab 3 mg/kg q3w and subsequent nivolumab 240 mg flat dose as monotherapy are given. Primary endpoint is overall response rate (ORR) of the upfront combination therapy. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. Results: The SCLC cohort was amended to include TMB high patients only, after two treatment-related deaths had occurred and emerging data indicated treatment benefit depends on high TMB status for the combination therapy. Both patients with treatment-related death had a CT-scan documented partial response (not confirmed according to RECIST due to death). One each died of pneumonitis and encephalitis. From the all-comer cohort, efficacy data are available for 18 patients. ORR was 38.8% with 7 partial and no complete responses. Stable disease occurred in 16.7% (n = 3) resulting in a DCR of 55.5%. TMB pre-screening for the amended cohort is currently ongoing. Conclusions: In the SCLC cohort, upfront combination therapy of nivolumab and ipilimumab shows remarkable ORR but is accompanied by high toxicity rates. In order to ensure a reasonable balance of risks and treatment benefit, only TMB high patients are included after an amendment of the cohort to improve the risk/benefit ratio. Clinical trial information: NCT03083691.