1575PPreliminary results from phase Ib study of spartalizumab plus chemotherapy for advanced non-small cell lung cancer (NSCLC)

Abstract Background Spartalizumab (PDR001) is an anti-PD-1 monoclonal antibody that is been explored in different tumor types. Preliminary safety and efficacy results from Groups B (B) and C (C) of a phase Ib study investigating spartalizumab with platinum-based chemotherapy in PD-L1 unselected advanced NSCLC (NCT03064854) are reported here. Methods Treatment-naive, stage IIIB/IV NSCLC, EGFR/ALK/ROS-1(-) pts, PS 0-1, were assigned to B (non-squamous NSCLC) or C (squamous/non-squamous NSCLC) for 4 cycles (21 day/cycle) of spartalizumab (initial dose – 300 mg Q3W) + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 followed by maintenance spartalizumab + pemetrexed (in B), or 4 cycles of spartalizumab (initial dose – 300 mg Q3W) + paclitaxel 200 mg/m2 + carboplatin AUC 6 followed by maintenance with spartalizumab (in C). Primary endpoints are recommended dose for expansion (RDE) and ORR by investigator assessment. Results At data cutoff of 15 May 2019, 38 pts in B and 33 pts in C were treated; 14 pts (36.8%) in B and 4 pts (12.1%) in C are still receiving treatment. Primary reason for discontinuation was progressive disease: 13 of 38 pts (34.2%) in B and 25 of 33 pts (75.8%) in C. DLTs were grade 4 hyponatremia and grade 2 posterior reversible encephalopathy syndrome in B (2 pts) and grade 4 neutropenic colitis in C (1 pt). RDE of spartalizumab in combination with platinum-based chemotherapy for both groups was 300 mg Q3W. Most common AEs (≥50%, any grade) were nausea (73.7%) and neutropenia (50%) in B; neutropenia (57.6%) and anemia (54.5%) in C. ORR and complete response rate were 50% and 5.3% in B, and 51.5% and 3% in C. Median DOR (months; 95% CI) by investigator assessment was 13.8 (4.9, NE) in B and 8.2 (5.1, 15.4) in C. Median PFS (months; 95% CI) by investigator assessment was 10.4 (5.4, 15.0) in B and 6.3 (4.1, 10.1) in C. Responses were observed at different PD-L1 expression levels with higher rate in PD-L1 tumor proportion score (TPS) ≥ 50%. Assessment of additional immune biomarkers is ongoing. Conclusions RDE of spartalizumab in combination with platinum-based chemotherapy is 300 mg Q3W. Safety profile and preliminary clinical activity are consistent with prior experience with spartalizumab, other immune checkpoint inhibitors and chemotherapy treatments administered. Clinical trial identification NCT03064854. Editorial acknowledgement Shiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd, Hyderabad, India. Legal entity responsible for the study Novarti