OA15.05 BIOLUMA: A Phase II Trial of Nivolumab and Ipilimumab in Lung Cancer – Prospective Evaluation of TMB in SCLC Patients

Therapeutic options and prognosis for patients with small-cell lung cancer (SCLC) remain poor. Treatment with checkpoint inhibition can achieve remarkable responses, but this holds true for a small percentage of SCLC patients only. Recently, tumor mutation burden (TMB) emerged as promising predictive biomarker for nivolumab and ipilimumab combination therapy in terms of tumor response and overall survival in SCLC patients. Here, we present the SCLC TMB cohort of the BIOLUMA trial, which prospectively evaluates TMB as predictive biomarker in SCLC patients. 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 TMB only. FFPE tumor tissue is used for TMB pre-screening by whole exome sequencing (WES) at 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 combination therapy. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. The SCLC cohort was amended to include TMB high patients only, after two treatment-related deaths in the SCLC all-comer cohort had occurred and emerging data indicated treatment benefit depends on high TMB status for the combination therapy. TMB analysis seems to be feasible for most patients without the necessity of performing an additional tumor biopsy as evaluation of TMB on FFPE tumor tissue which was obtained at first diagnosis was sufficient in 90.1% of cases. To date, 53 patients are enrolled for pre-screening, sequencing result ist pending for 33 and TMB status has been determined for 20 patients. Of these, 45% belong to the TMB high group, while 55% have low or medium TMB. TMB pre-screening for the amended cohort is ongoing and enrolment of TMB high patients in the BIOLUMA trial recently started. Combination therapy of nivolumab and ipilimumab shows remarkable clinical results but is accompanied by high toxicity rates. Thus, in order to ensure a reasonable balance of risks and treatment benefits, it is an unmet need to evaluate predictive biomarker with TMB being the most promising which recently emerged in SCLC. To our knowledge, this is the first clinical trial which prospectively evaluates tumor mutation burden as predictive biomarker in SCLC patients. TMB screening is feasible on tumor material which is routinely obtained at first diagnosis.