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

Abstract

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\xa0day/cycle) of spartalizumab (initial dose – 300\xa0mg Q3W) + pemetrexed 500\xa0mg/m2 + cisplatin 75\xa0mg/m2 followed by maintenance spartalizumab + pemetrexed (in B), or 4 cycles of spartalizumab (initial dose – 300\xa0mg Q3W) + paclitaxel 200\xa0mg/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\xa0pt). RDE of spartalizumab in combination with platinum-based chemotherapy for both groups was 300\xa0mg 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\xa0mg 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 Novartis Pharmaceuticals Corporation. Funding Novartis Pharmaceuticals Corporation. Disclosure A. Santoro: Advisory / Consultancy: BMS, Servier, Gilead, Pfizer, Eisai, Bayer, Msd, Arqule; Speaker Bureau / Expert Testimony: Takeda, BMS, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, Astrazeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, MSD. P. Garrido Lopez: Advisory / Consultancy: Roche, MSD, BMS, Boerhinger Ingelheim, Pfizer, AbbVie, Guardant Health, Novartis, Lilly, AstraZeneca, Janssen, Sysmex, Blueprint Medicines, Takeda; Speaker Bureau / Expert testimony: Roche, MSD, BMS, Pfizer, Novartis, Boerhinger Ingelheim, Rovi; Research grant / Funding (institution), For Clinical Trails: Roche, MSD, BMS, Takeda, Lilly, Pfizer, Novartis, PharmaMar, Celgene, Sanofi, GSK, Theradex Oncology, BluePrint Medicines; Research grant / Funding (institution), For Contracted Research: Guardant Health, Sysmex. D.S.W. Tan: Honoraria (self): Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda ; Advisory / Consultancy: Novartis, Bayer, Boehringer Ingelheim, Celgene, AstraZeneca, Eli-lily, Loxo; Research grant / Funding (self): Novartis, AstraZeneca, GlaxoSmithKline, Bayer, Pfizer ; Travel / Accommodation / Expenses: Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche,Takeda . L. Paz-Ares: Honoraria (self): Roche, Novartis, Pfizer, Lilly, BMS, MSD, Merck, Boehringer Ing., AstraZeneca, Amgen, Sanofi, PharmaMar, Takeda; Leadership role: Genomica. F. Shepherd: Honoraria (self): Novartis, AstraZeneca, Roche, BMS, Merck, EMD Serono; Advisory / Consultancy: Novartis, AstraZeneca, Roche, BMS, Merck, EMD Serono; Shareholder / Stockholder / Stock options: AstraZeneca. A. Bearz: Advisory / Consultancy: Takeda; Boehringer Ingelheim, Roche , MSD, Novartis; Speaker Bureau / Expert testimony: Takeda; Boehringer Ingelheim, Roche , MSD; Pfizer; Research grant / Funding (institution): AstraZeneca. F. Barlesi: Honoraria (self): AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda; Research grant / Funding (institution): AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer–Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, MedImmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-remunerated activity/ies: Principal Investigator for AstraZeneca, BMS, Merck, Pierre Fabre and F. Hoffmann-La Roche, Ltd, sponsored trials (or ISR). J.F. Vansteenkiste: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Roche, Apotex; Research grant / Funding (institution): MSD. T.M. Kim: Research grant / Funding (institution): Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan ; Research grant / Funding (self): AstraZeneca ; Non-remunerated activity/ies, Advisory / Consultancy: AstraZeneca, Novartis, Sanofi, and Bayer . T.R. Overbeck: Advisory / Consultancy, Consulting fees: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Medac, MSD, Novartis, Roche/Genentech; Research grant / Funding (institution), sponsored research agreements: AstraZeneca, Eli Lilly, Roche/Genentech, Sanofi-Aventis; Travel / Accommodation / Expenses, Travel Support: AstraZeneca, Boehringer Ingelheim, Eli Lilly and Roche/Genentech. I.I. Rybkin: Research grant / Funding (institution): Merck, AbbVie, ARMO Biosciences, Beyond Spring Pharmaceutical, Bristol-Myers Squibb, Novartis, Mirati Therapeutical Inc., Nilogen, Inc., Pfizer, Polaris Group, Syndax Inc., Xcovery Inc., BerGenBio AS, Incyte Corporation, AstraZeneca, Amgen; Advisory / Consultancy: AstraZeneca. E. Felip: Advisory / Consultancy: AbbVie, AstraZeneca, Blue Print Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Helath, Janssen, Medscape, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Speaker Bureau / Expert Testimony: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Kgaa, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; Research Grant / Funding (Self): Fundacion Merck Salud Grant For Oncology Innovation Emd Serono. W. Zhou: Full / Part-time employment: Novartis. L. Santarpia: Full / Part-time employment: Novartis. S. Eddy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Novartis. All other authors have declared no conflicts of interest.