Abstract 1315P
Background
The MORPHEUS platform comprises multiple phase Ib/II trials to identify early efficacy signals and safety of treatment combinations across cancers. Within MORPHEUS, atezo, a PD-L1 inhibitor, was tested in combination with CPI-444, an adenosine-A2A inhibitor, in patients with metastatic NSCLC.
Methods
MORPHEUS-NSCLC enrolled patients who had disease progression during or after receiving a platinum-based regimen and a PD-L1/PD-1 checkpoint inhibitor, given in combination as 1 line of therapy or as 2 separate lines of therapy. Patients in the atezo + CPI-444 arm received atezo 1200 mg intravenously (IV) on Day 1 of each 21-day cycle plus CPI-444 100 mg orally twice daily on Days 1–21. Control treatment was docetaxel 75 mg/m2 IV on Day 1 of each 21-day cycle. Primary endpoints were confirmed objective response rate (ORR; investigator [INV]-assessed per RECIST 1.1) and safety. Secondary endpoints included progression free survival (PFS; INV-assessed per RECIST 1.1) and overall survival (OS).
Results
As of February 14, 2020, 15 patients received atezo + CPI-444 and 14 patients received docetaxel. In the atezo + CPI-444 arm, 1 patient has an ongoing partial response (PR; > 14 mo) for a confirmed ORR of 6.7%. Of the 6 patients (40%) with stable disease (SD), 1 SD has been ongoing for > 15 mo. Two patients (13.3%) still on treatment were PD-free at 12 mo. In the docetaxel arm, 3 patients had PR, for a confirmed ORR of 21.4%, and 5 patients (36%) had SD. All patients in the docetaxel arm have discontinued treatment. Median PFS was 2.3 mo and 3.2 mo (HR, 1.0; 95% CI: 0.4, 2.3) in the atezo + CPI-444 and docetaxel arms, respectively. No patients receiving atezo + CPI-444 had Grade 5 AEs or AEs that led to treatment withdrawal. Of the patients receiving docetaxel, 1 experienced a Grade 5 AE and 4 had AEs that led to treatment withdrawal. OS, biomarker and PK data will be presented.
Conclusions
Confirmed responses were seen in 1 patient receiving atezo + CPI-444 and in 3 patients receiving docetaxel in this small, randomised study. No new safety signals were observed, and AEs were in line with the known safety profile of individual study treatments.
Clinical trial identification
NCT03337698.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Bena Lim, PhD of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study
The legal entity is F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
E. Felip: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy: Blueprint Medicines; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy: Celgene; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy: Guardant Health; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Speaker Bureau/Expert testimony: Medscape; Honoraria (self), Advisory/Consultancy: Merck KGaA; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (self), Speaker Bureau/Expert testimony: prIME Oncology; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy: Samsung; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Speaker Bureau/Expert testimony: Touchime; Honoraria (self), Advisory/Consultancy: GSK; Honoraria (self), Advisory/Consultancy: Bayer. F.L. Lim: Advisory/Consultancy: Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: GLG Consultancy; Advisory/Consultancy: Pfizer. M. Johnson: Research grant/Funding (institution): AbbVie, Acerta, Adaptimmune, Apexigen, Array Biopharma, AstraZeneca, Atreca; Research grant/Funding (institution): BeiGene, Boehringer Ingelheim, Checkpoint Therapeutics, Corvus Pharmaceuticals, CytomX; Research grant/Funding (institution): Daiichi Sankyo, Dynavas, Lilly, EMD Serono, Genentech/Roche, Genmab, Genocea Biosciences, GSK; Research grant/Funding (institution): Gritstone Oncology, Guardant Health, Hengrui Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics; Research grant/Funding (institution): Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Merck, Mirati Therapeutics, Neovia Oncology, Novartis, OncoMed Pharmaceuticals; Research grant/Funding (institution): Pfizer, Regeneron, Sanofi, Seven and Eight Pharmaceuticals, Shattuck Labs, Stem CentRx, Syndax Pharmaceuticals; Research grant/Funding (institution): Takeda Pharmaceuticals, Tarveda, University of Michigan, WindMIL, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, Amgen; Honoraria (self), Spouse/Financial dependant: Astellas, Otsuka Pharmaceuticals; Honoraria (self): AbbVie, Achilles Therapeutics, AstraZeneca, Atreca, Boehringer Ingelheim, Calithera Biosciences; Honoraria (self): Genentech, GSK, Gritstone Oncology, Guardant Health, Incyte; Honoraria (self): Janssen, Lilly, Loxo Oncology, Merck, Mirati Therapeutics; Honoraria (self): Novartis, Pfizer, Ribon Therapeutics, Sanofi, Association of Community Cancer Centers; Travel/Accommodation/Expenses: AbbVie, Astellas, AstraZeneca, Boehringer Ingelheim; Travel/Accommodation/Expenses: Clovis, Daiichi Sankyo, EMD Serono, Bristol-Myers Squibb, Exelixis; Travel/Accommodation/Expenses: Genentech/Roche, Incyte, Merck, Pfizer; Travel/Accommodation/Expenses: Sysmex Inostics, Vapotherm, Janssen, Lilly, Novartis, Sanofi. F. Barlesi: Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Honoraria (institution): Bayer; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: BMS; Honoraria (self), Honoraria (institution): Boehringer Ingelheim; Honoraria (self), Honoraria (institution): Eli Lilly Oncology; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Roche; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Merck; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution), Non-remunerated activity/ies: Pierre Fabre; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): Takeda; Honoraria (institution): AbbVie; Honoraria (institution): ACEA; Honoraria (institution): Amgen; Honoraria (institution): Eisai; Honoraria (institution): Genentech; Honoraria (institution): Ipsen; Honoraria (institution): Ignyta; Honoraria (institution): Innate Pharma; Honoraria (institution): Loxo; Honoraria (institution): MedImmune; Honoraria (institution): Sanofi-Aventis. J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Merck & Co.; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Hengruii; Advisory/Consultancy: Daiichi; Advisory/Consultancy: Boehringer ; Advisory/Consultancy: Takeda. B. Solomon: Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Loxo Oncology; Honoraria (self), Advisory/Consultancy: Amgen. V. Moreno: Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer. V. Boni: Advisory/Consultancy: Ideaya Biosciences; Advisory/Consultancy: Loxo Therapeutics. A. Swalduz: Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca. S. Goldberg: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy: Amgen; Advisory/Consultancy: BMS; Advisory/Consultancy: Genentech; Advisory/Consultancy: Spectrum; Advisory/Consultancy: Eli Lilly. B. Keam: Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Merck & Co. Oncology; Advisory/Consultancy: Genexin; Research grant/Funding (self): Ono Pharmaceutical. S. Allen: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche. H-J. Helms, J. Pintoffl, P. Sayyed: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. C. Shemesh: Shareholder/Stockholder/Stock options: Genentech. N. Al-Sakaff, L. Bailey: Full/Part-time employment: Roche. B.C. Cho: Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): MOGAM Institute; Research grant/Funding (self): Dong-A ST; Research grant/Funding (self), Licensing/Royalties: Champions Oncology; Advisory/Consultancy, Research grant/Funding (self): Janssen; Advisory/Consultancy, Research grant/Funding (self): Yuhan; Advisory/Consultancy, Research grant/Funding (self): Ono; Research grant/Funding (self): Dizal Pharm; Advisory/Consultancy, Research grant/Funding (self): MSD; Research grant/Funding (self): AbbVie; Advisory/Consultancy: Medpacto; Research grant/Funding (self): GIInovation, Eli Lilly; Advisory/Consultancy, Research grant/Funding (self): Blueprint Medicines; Shareholder/Stockholder/Stock options: TherCanVac Inc, Gencurix Inc, Bridgebio Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Kanaph Therapeutics Inc; Advisory/Consultancy: Takeda, Pfizer, BMS, Boehringer Ingelheim; Officer/Board of Directors: Daan Therapeutics. All other authors have declared no conflicts of interest.