LBA42 - COAST: An open-label, randomised, phase II platform study of durvalumab alone or in combination with novel agents in patients with locally advanced, unresectable, stage III NSCLC

Background

PACIFIC established consolidation durvalumab (D) as SoC for unresectable Stage III NSCLC with no progression after cCRT. Combination therapy may improve outcomes. CD73 is involved in RT resistance. RT induces NKG2A ligand and shows additive antitumour effects with PD-1 blockade preclinically. COAST (NCT03822351) is a global phase 2 study of D alone or combined with the anti-CD73 mAb oleclumab (O) or anti-NKG2A mAb monalizumab (M) as consolidation therapy.

Methods

Pts with histologically/cytologically documented unresectable Stage III NSCLC, ECOG PS 0/1 and no progression after cCRT were randomised 1:1:1 ≤42 days post cCRT to receive D 1500 mg IV Q4W alone or combined with O 3000 mg IV Q2W (first 2 cycles, then Q4W) or M 750 mg IV Q2W for up to 12 months, stratified by histology. The primary endpoint was investigator-assessed post cCRT ORR per RECIST v1.1. Key secondary endpoints included PFS and safety.

Results

Between Jan 2019 and Jul 2020, 189 pts were randomised, of whom 186 received D (n=66), D+O (n=59) or D+M (n=61). As of 17 May 2021, median follow-up was 11.5 months (range, 0.4–23.4; all pts). D+O and D+M numerically increased ORR (odds ratio [95% CI] 1.83 [0.80, 4.20] and 1.77 [0.77, 4.11] respectively) and significantly improved PFS versus D alone. Grade ≥3 treatment-emergent AE (TEAE, all-cause) incidence was 39.4%, 40.7% and 27.9% with D, D+O and D+M respectively. Overall, the most common grade 3/4 TEAEs were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were more common with D and D+O than with D+M. Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with D, 28.8% with D+O and 21.3% with D+M, with grade ≥3 events in 3.0%, 3.4% and 1.6%. Biomarker data will be presented.

Conclusions

Addition of both novel agents improved ORR, PFS and 10-month PFS rate over D alone. Safety was similar across arms with no new safety signals identified. Table: LBA42

^aConfirmed and unconfirmed ^b95% CI by Clopper-Pearson exact method ^c10-month minimum follow-up for all pts; Kaplan-Meier estimates for PFS, PFS rate and 95% CIs^dPFS HR and 95% CI estimated by Cox regression model, stratified by histology ^eCompared to 67 D+O pts and 64 D+M pts enrolled concurrently with D pts

Clinical trial identification

NCT03822351 (release date: January 30, 2019).

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Connor Keating, BSc, and Andrew Gannon, MS, MA, of Ashfield MedComms (New York, NY), an Ashfield Health company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

A. Martinez-Marti: Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: F Hoffmann-La Roche; Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: Merck Sharp and Dohme; Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: Pfizer; Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: MSD Oncology; Financial Interests, Personal, Other, Honoraria/Advisory Board, Personal Fees and Travel Expenses: Boehringer Ingelheim. M. Majem: Financial Interests, Personal, Other, Honorarium received from promotional activities: Bristol Myers Squibb; Financial Interests, Personal, Other, Honorarium received from promotional activities: MSD; Financial Interests, Personal, Other, Honorarium received from promotional activities: Boehringer Ingelheim; Financial Interests, Personal, Other, Honorarium received from promotional activities: AstraZeneca; Financial Interests, Personal, Other, Honorarium received from promotional activities: Roche; Financial Interests, Personal, Other, Honorarium received from promotional activities: Kyowa Kirin; Financial Interests, Personal, Other, Honorarium received from promotional activities: Pierre Fabre; Financial Interests, Personal, Other, Honorarium received from promotional activities: Takeda; Financial Interests, Personal, Other, Honorarium received from promotional activities: Bayer; Financial Interests, Personal and Institutional, Research Grant, Contracted support/research grant: Bristol Myers Squibb. F. Barlesi: Financial Interests, Personal, Other, Personal Fees: AstraZeneca; Financial Interests, Personal, Other, Personal Fees: Bayer; Financial Interests, Personal, Other, Personal Fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Personal Fees: Boehringer Ingelheim; Financial Interests, Personal, Other, Personal Fees: Eli Lilly; Financial Interests, Personal, Other, Personal Fees: F Hoffmann-La Roche; Financial Interests, Personal, Other, Personal Fees: Novartis; Financial Interests, Personal, Other, Personal Fees: Merck; Financial Interests, Personal, Other, Personal Fees: MSD; Financial Interests, Personal, Other, Personal Fees: Pierre Fabre; Financial Interests, Personal, Other, Personal Fees: Pfizer; Financial Interests, Personal, Other, Personal Fees: Takeda. Q. Chu: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Takeda; Other, Personal, Member, Data Safety and Monitoring Board: Merck KgAa; Financial Interests, Personal, Writing Engagements: Kaleidoscope Strategic Inc.; Non-Financial Interests, Personal, Leadership Role: Lung Cancer Canada; Non-Financial Interests, Personal, Leadership Role: Canadian Mesothelioma Foundation; Financial Interests, Personal, Research Grant: Exactis. I. Monnet: Non-Financial Interests, Personal, Other, ESMO 2019 Congress Invitation: Pfizer; Non-Financial Interests, Personal, Other, ESMO 2018 Congress Invitation: Roche. A. Sanchez: Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Janssen; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Eli Lilly; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Amgen; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Roche; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: MSD; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Novartis; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Sanofi; Financial Interests, Personal, Other, Honoraria, Personal Fees and Travel Expenses: Pfizer. D.R. Camidge: Financial Interests, Personal, Other, Personal Fees: AstraZeneca. P. He: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. Y. Soo-Hoo: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Z. Cooper: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Kumar: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Other, Personal, Other, Patent planned/pending: AstraZeneca. J. Bothos: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C. Aggarwal: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Roche. R.S. Herbst: Financial Interests, Personal, Other, Personal Fees: AbbVie; Financial Interests, Personal, Other, Personal Fees: ARMO Biosciences; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other, Personal fees: Biodesix; Financial Interests, Personal, Other, Personal fees: Bolt Biotherapy; Financial Interests, Personal, Other, Personal fees: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Eli Lilly and Company; Financial Interests, Personal, Other, Personal fees: EMD Serono; Financial Interests, Personal and Institutional, Research Grant: Genentech/Roche; Financial Interests, Personal, Other, Personal fees: Genmab; Financial Interests, Personal, Other, Personal fees: Halozyme; Financial Interests, Personal, Other, Personal fees: Heat Biologics; Financial Interests, Personal, Other, Personal fees: IMAB Biopharma; Financial Interests, Personal, Other, Personal fees: Immunocore; Financial Interests, Personal, Other, Personal fees: Infinity Pharmaceuticals; Other, Personal, Member, Board Member (non-executive/ independent): Junshi Pharmaceuticals; Financial Interests, Personal, Other, Personal fees: Loxo Oncology; Financial Interests, Personal and Institutional, Research Grant: Merck and Company; Financial Interests, Personal, Other, Personal fees: Mirati Therapeutics; Financial Interests, Personal, Other, Personal fees: Nektar; Financial Interests, Personal, Other, Personal fees: Neon Therapeutics; Financial Interests, Personal, Other, Personal fees: NextCure; Financial Interests, Personal, Other, Personal fees: Novartis; Financial Interests, Personal, Other, Personal fees: Seattle Genetics; Financial Interests, Personal, Other, Personal fees: Shire PLC; Financial Interests, Personal, Other, Personal fees: Spectrum Pharmaceuticals; Financial Interests, Personal, Other, Personal fees: Symphogen; Financial Interests, Personal, Other, Personal fees: Takeda; Financial Interests, Personal, Other, Personal fees: Tesaro; Financial Interests, Personal, Other, Personal fees: Tocagen; Financial Interests, Personal, Other, Personal fees: Cybrexa; Financial Interests, Personal, Other, Personal fees: Oncternal Therapeutics; Financial Interests, Personal, Other, Personal Fees: Pfizer; Financial Interests, Personal, Other, Personal Fees: Sanofi. All other authors have declared no conflicts of interest.