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.

Abstract

e20550 Background: Patient selection, dosing regimens and resistance mechanisms for immune checkpoint inhibitor combination therapy remain unmet medical needs in lung cancer. Combining blockade of PD-1 and CTLA-4 can be more effective than monotherapy but is accompanied by an increase in toxicity. Thus, to circumvent unnecessary toxicity it is of great interest to identify patients who will benefit from PD-1/PD-L1 blockade alone and to add ipilimumab only in case of primary or secondary progression. We present interim data from the non-small-cell lung cancer (NSCLC) 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 a multicentre non-randomised phase II trial in 2nd line patients with non-squamous NSCLC. Patients are treated with nivolumab 240 mg until disease progression and subsequently with a combination therapy of nivolumab 3 mg/kg q2w and ipilimumab 1mg/kg q6w. Primary endpoint is overall response rate (ORR) after addition of ipilimumab to nivolumab treatment. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. Results: To date, 26 patients have been enrolled and 9 patients were transferred to the combination therapy after progression on nivolumab monotherapy. Drop out rate between the treatment arms is high, mainly due to rapid disease progression and adverse events which don’t allow addition of ipilimumab. ORR is available for 8 of these patients: 6 patients (75%) had PD as best response, and 1 (12.5%) each had a stable disease and partial response, respectively. The patient who achieved a PR had experienced primary tumor progression on nivolumab monotherapy before. Toxicity rate was similar to what has been reported from other trials. Conclusions: In NSCLC, addition of ipilimumab to nivolumab in nivolumab refractory patients seems to be safe, but the response rate is low and the drop out between the treatment parts high. Given these data, early termination of this cohort is currently discussed. Clinical trial information: NCT03083691.