Abstract 5069
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
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): Fundación 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.
Resources from the same session
4242 - HIV, HBV and HCV screening practices in oncology: a cross-sectional interregional survey
Presenter: Isabelle Poizot-Martin
Session: Poster Display session 1
Resources:
Abstract
1267 - Genetic landscape of KEAP1 and NFE2L2 mutated cancers from the AACR GENIE database
Presenter: Mark Zaki
Session: Poster Display session 1
Resources:
Abstract
878 - β-arrestin1 is involved in the Ras-induced malignant transformation
Presenter: Takashi Shibano
Session: Poster Display session 1
Resources:
Abstract
4143 - Incidence of second cancer among PLWHIV: retrospective observational study of a series of 601 patients in the French CANCERVIH network
Presenter: Jean-Philippe Spano
Session: Poster Display session 1
Resources:
Abstract
5145 - A challenging task – Identifying carcinoma of unknown primary (CUP) patients according to ESMO guidelines: the CUPISCO trial experience
Presenter: Chantal Pauli
Session: Poster Display session 1
Resources:
Abstract
1737 - Incidence and Outcome of chronic lymphocytic leukemia with Deletion 17p: An Indian experience; challenges and opportunities
Presenter: Ajay Gogia
Session: Poster Display session 1
Resources:
Abstract
2596 - Driving solo? Investigation into collaborating mutations in SDH-deficient neoplasia
Presenter: Jonathan Killian
Session: Poster Display session 1
Resources:
Abstract
1499 - The potential of a novel antiangiogenic VEGFR1-D2 binding peptide in oncology therapeutics
Presenter: Afsaneh Sadre Momtaz
Session: Poster Display session 1
Resources:
Abstract
1775 - First-in-human phase I study of TAS-117, an allosteric AKT inhibitor, in patients with advanced solid tumors
Presenter: Mayu Yunokawa
Session: Poster Display session 1
Resources:
Abstract
4584 - First-in-human study of ABBV-621 in patients (pts) with previously treated sold tumors: Dose-optimization cohorts
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract