Abstract 1209MO
Background
Neoadjuvant (neo) and perioperative immune checkpoint blockade (ICB) have revolutionized the treatment of resectable non-small cell lung cancer (NSCLC). We report the first pooled analysis of 5-year clinical outcomes from 2 early phase trials of neo ICB in NSCLC – NEOSTAR & CA209-159.
Methods
In NEOSTAR (NCT03158129), patients (pts) were randomized 1:1 to IV nivolumab (N) 3mg/kg every 2 weeks (q2w) x 3 (doses) with (w/) or without IV ipilimumab (I) 1mg/kg on day 1 only. In CA209-159 (NCT02259621), pts were enrolled into sequential arms: N 3mg/kg q2w x 2, N 3 mg/kg q2w x 3 w/ I 1mg/kg on day 1 only, N 3mg/kg q2w x 3. Both trials enrolled pts w/ stage I-IIIA NSCLC (AJCC 7th). Individual pt data meta-analysis to account for cohort effect was performed to estimate weighted major pathologic response (MPR), pathologic complete response (PCR), event-free (EFS), and overall survival (OS) rates and hazard ratios (HR).
Results
60 pts were treated w/ N and 30 w/ NI. MPR rates were 28.1% (95% CI: 17.4, 42.1) and 33.3% (95% CI: 19.0, 51.7) in N and NI cohorts, respectively. PCR rates were 8.3% (95% CI: 3.5, 18.5) and 26.7% (95% CI: 13.9, 45.0), respectively. At median (m) follow-up of 68.4 months (mo) in N and 62.1mo in NI, mEFS and mOS were not reached in either group. In the combined 90 pt cohort, pts w/ MPR had a 5-year EFS and OS of 74.0% (95% CI 52.9, 86.8) and 81.7% (95% CI: 61.4, 92.0), respectively. Pts w/ PCR had a 5-year EFS and OS of 77.5% (95% CI: 44.9, 92.2) and 85.5% (95% CI: 52.9, 96.2), respectively. MPR was associated w/ trend toward improved EFS w/ NI but not N. In N, pre-treatment PD-L1 ≥1% was associated w/ significantly improved EFS. In N, but not NI, known KRAS co-mutation w/ STK11, KEAP, and/or SMARCA4 was associated w/ significantly worse EFS. Table: 1209MO
| EFS Cox Regression∗ | N cohort | NI cohort | ||||||
| Factor | Event | Total | HR (95% CI) | p | Event | Total | HR (95% CI) | p |
| Stage (AJCC 7th) | ||||||||
| I/II | 16 | 45 | Ref | 9 | 20 | Ref | ||
| IIIA | 8 | 15 | 2.00 (0.85, 4.69) | 0.113 | 6 | 10 | 2.03 (0.69, 6.02) | 0.201 |
| Pre-treatment PD-L1 | ||||||||
ConclusionsNeo ICB w/ N and NI demonstrates favorable long-term clinical efficacy in resectable NSCLC. Biomarker-driven studies are needed to identify pt subgroups who would benefit from neo single or combined ICB. Clinical trial identificationNCT03158129; NCT02259621. Editorial acknowledgementLegal entity responsible for the studyThe authors. FundingBMS, NCI/NIH, Conquer Cancer Foundation of ASCO, Stand up 2 Cancer, LUNGevity Foundation, International Immuno-Oncology Network, IASLC, Prevent Cancer Foundation, Lung cancer Foundation of America, MacMillan Foundation, ECOG-ACRIN, Johns Hopkins Sidney Kimmel Cancer Center, MD Anderson Cancer Center, Memorial Sloan Kettering, Cancer Center, Khalifa Bin Zayed Al Nahyan Foundation, Ford Petrin Donation, Rexanna’s Foundation for Fighting Lung Cancer, Bob Mayberry Foundation. DisclosureJ. Reuss: Financial Interests, Personal, Advisory Board: Guardant, AstraZeneca, Bristol Myers Squibb, Arcus, AbbVie, Catalym, Seagen, Gilead, Janssen, Novocure, Regeneron, Summit Therapeutics, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Genentech/Roche; Financial Interests, Institutional, Local PI: Verastem, Nuvalent, Exelixis. S. Rosner: Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Other, Honoraria: MJH Life Sciences, Dava Oncology, EM Partners, Cardinal Health, Life Sciences FGI, Axiom. W. Nassib William Junior: Financial Interests, Personal, Invited Speaker: Amgen, Genentceh / Roche, Eli Lilly, BMS, Pfizer, Janssen, United Medical; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Merck, Bayer, Sanofi, Takeda, Novartis. S. Broderick: Financial Interests, Personal, Advisory Role: BMS. J.D. Spicer: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, Roche, BMS, Novartis, Amgen, Protalix Biotherapeutics, Xenetic Biosciences, Regeneron, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck, BMS; Financial Interests, Institutional, Coordinating PI, In kind contribution of investigational drug.: AstraZeneca, BMS; Financial Interests, Institutional, Coordinating PI, Grant to institution for research within my laboratory.: CLS Therapeutics; Financial Interests, Institutional, Coordinating PI, Grant to institution for execution of research within my laboratory.: Protalix Biotherapeutics; Financial Interests, Institutional, Coordinating PI, Grant to institution for execution of multi-center clinical trial.: Roche; Financial Interests, Institutional, Coordinating PI, Grant to institution for execution of clinical trial.: Merck; Non-Financial Interests, Principal Investigator, Clinical trial chair for IND 242 Neoadjuvant Platform Trial in Patients with Surgically Resectable Non-Small Cell Lung Cancer (NSCLC): Canadian Cancer Trials Group. D.R. Jones: Financial Interests, Institutional, Research Funding: Merck; Financial Interests, Personal, Advisory Board: AstraZeneca, Medtronic; Financial Interests, Personal, Other, Clinical Trial Steering Committee: AstraZeneca; Financial Interests, Personal, Advisory Role: NCI. J.V. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co., Janssen Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK, Spectrum; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Institutional, Other, International PI for clinical trials: AstraZeneca; Financial Interests, Institutional, Other, International PI for two clinical trials: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Institutional, Coordinating PI: Takeda. B. Sepesi: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca. J. Chaft: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Genentech, Merck, Regeneron, Sanofi, Guardant Health, Lilly, Janssen; Financial Interests, Institutional, Research Funding: AstraZeneca, BMS, Genentech, Merck, Novartis, Beigene. P.M. Forde: Financial Interests, Institutional, Research Funding: AstraZeneca, BMS, Novartis, Regeneron, BioNTech; Financial Interests, Personal, Advisory Board: Ascendis, AstraZeneca, BMS, Curevac, Foresight, Novocure, Regeneron, G1, Genelux, Genentech, Gritstone, Merck, Janssen, F Star, Sanofi, Amgen, Fosun, Teva, Synthekine, Iteos, Tavotek, Veracyte. T. Cascone: Financial Interests, Personal, Invited Speaker, Speaker Fees/Co-Chair Honorarium: AstraZeneca; Financial Interests, Personal, Invited Speaker, Speaker Fees/Interview Honorarium: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory Board Fees: AstraZeneca, Bristol Myers Squibb, Pfizer; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meeting/Conference as Invited Panelist/Co-Chair: AstraZeneca; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Advisory Board as Invited Member: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, Speaker Fee: Clinical Care Options, Peerview, Physician's Education Resource; Financial Interests, Personal, Invited Speaker, Speaker Fees/Invited Panelist Honoraria: IDEOlogy Health; Financial Interests, Personal, Other, Conference Co-Chair Honorarium: IDEOlogy Health; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meetings as Invited Speaker or Conference Co-Chair: IDEOlogy Health; Financial Interests, Personal, Invited Speaker, Speaker Fee/Panelist Honorarium: Medscape; Financial Interests, Personal, Invited Speaker, Speaker Fees/Panelist Honoraria: OncLive; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meeting as Invited Speaker and Panelist: OncLive; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses to Meeting as Invited Speaker: Physician's Education Resource; Financial Interests, Personal, Other, Grant Reviewer Honorarium: Mark Foundation For Cancer Research; Financial Interests, Personal, Advisory Board, Advisory Board Fee: Merck, Regeneron; Financial Interests, Personal, Other, Travel/Food/Beverage for Advisory Board as Invited Member: Merck; Financial Interests, Personal, Other, Travel Expenses For Conferences as Invited Speaker: ESMO; Financial Interests, Personal, Other, Speaker Fee and Travel Expenses For Conferences as Invited Speaker: SITC; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses For Conferences as Invited Speaker: IASLC; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses for Meeting as Invited Panelist: AATS; Financial Interests, Personal, Other, Travel/Food/Beverage Expenses for Conference as Invited Speaker: Dava Oncology; Financial Interests, Institutional, Coordinating PI, Institutional Clinical Research Funding: AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Institutional Research Grant Funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Steering Committee Member, Clinical Research: AstraZeneca; Non-Financial Interests, Leadership Role, The Leading Edge of Cancer Research Symposium Co-chair and Chair (2021 and 2022)Co-Chair, Data and Biospecimen Access Committee (DBAC), 2022 – present: The University of Texas MD Anderson Cancer Center; Non-Financial Interests, Leadership Role, Co-Chair, Neoadjuvant Immunotherapy Session, 36th SITC Annual Meeting, 11/2021: SITC; Non-Financial Interests, Leadership Role, Co-Chair, Texas Lung Cancer Conference 2023, and 2024. Austin, TX 4/2023 and 4/2024.: IDEOlogy Health; Non-Financial Interests, Leadership Role, Co-Chair, The Future of immunotherapy in Thoracic Oncology, Educational Session, ESMO Immuno-Oncology Congress, Geneva, Switzerland, 12/6/2023: ESMO; Non-Financial Interests, Leadership Role, Co-Chair, Lung Cancer Summit Post-ESMO Congress 2023, sponsored by AstraZeneca, Madrid, Spain 10/24-10/25/2023: AstraZeneca; Non-Financial Interests, Leadership Role, Chair, Early-Stage NSCLC Session. IASLC Targeted Therapies of Lung Cancer Meeting (TTLC) 2021, Santa Monica, CA, 2/2021Chair, IASLC 2022 World Conference on Lung Cancer, Neoadjuvant and Adjuvant Treatment of NSCLC Session, Vienna, Austria, 8/2022Chair, IASLC 2022 World Conference on Lung Cancer, Immune Landscape and Molecular Profiling of Lung Cancer Session, Vienna, Austria, 8/2022Chair, IASLC 2023 World Conference on Lung Cancer, Pushing the Boundaries: Adjuvant and Neoadjuvant Approaches in Early-Stage Non-small Cell Lung Cancer, Singapore 9/2023: IASLC; Non-Financial Interests, Member: ESMO, ASCO, AACR, SITC, IASLC; Other, Food/Beverage Expenses at Conferences: Genentech, Daiichi Sankyo. All other authors have declared no conflicts of interest. 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