Integration of immunotherapy into adjuvant therapy for resected non-small-cell lung cancer: ALCHEMIST chemo-IO (ACCIO)

Jacob M Sands, Sumithra J Mandrekar, David Kozono, Geoffrey R Oxnard, Shauna L Hillman, Dennis A Wigle, Ramaswamy Govindan, Jennifer Carlisle, Jhanelle Gray, Joseph K Salama, Luis Raez, Apar Ganti, Nathan Foster, Shakun Malik, Jeffrey Bradley, Karen Kelly, Suresh S Ramalingam, Thomas E Stinchcombe, Jacob M Sands, Sumithra J Mandrekar, David Kozono, Geoffrey R Oxnard, Shauna L Hillman, Dennis A Wigle, Ramaswamy Govindan, Jennifer Carlisle, Jhanelle Gray, Joseph K Salama, Luis Raez, Apar Ganti, Nathan Foster, Shakun Malik, Jeffrey Bradley, Karen Kelly, Suresh S Ramalingam, Thomas E Stinchcombe

Abstract

Non-small-cell lung cancer (NSCLC) causes significant mortality each year. After successful resection of disease stage IB (>4 cm) to IIIA (per AJCC 7), adjuvant platinum-based chemotherapy improves median overall survival and is the standard of care, but many patients still experience recurrence of disease. An adjuvant regimen with greater efficacy could substantially improve outcomes. Pembrolizumab, a programmed cell death-1 inhibitor, has become an important option in the treatment of metastatic NSCLC. ALCHEMIST is a clinical trial platform of the National Cancer Institute that includes biomarker analysis for resected NSCLC and supports therapeutic trials including A081801 (ACCIO), a three-arm study that will evaluate both concurrent chemotherapy plus pembrolizumab and sequential chemotherapy followed by pembrolizumab to standard of care adjuvant platinum-based chemotherapy. Clinical trial registration: NCT04267848 (ClinicalTrials.gov).

Keywords: NSCLC; adjuvant chemotherapy; lung adenocarcinoma; lung squamous cell carcinoma; pembrolizumab.

Conflict of interest statement

Financial & competing interests disclosure

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), UG1CA233180, UG1CA233253, UG1CA233247, UG1CA233339, and UG1CA232760. https://acknowledgments.alliancefound.org. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. JM Sands reports honoraria for consulting from AstraZeneca, Takeda, Boehringer Ingeheim, Medtronic, Jazz Pharmaceuticals, Pharma Mar, Blueprint Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Loxo, Foundation Medicine, Guardant and Abbvie. GR Oxnard reports employment with Foundation Medicine and equity in Roche. R Govindan reports honoraria for advisory board from Genentech, Pfizer, Roche, Nektar, Bristol Myers Squibb, Partner Therapeutics, GlaxoSmithKline, Jounce and Achilles; and consulting from AstraZeneca, Amgen, Horizon Pharmaceuticals, GenePlus and Inivata. J Gray reports honoraria for consulting from AstraZeneca, Blueprint Medicines, Bristol Myers Squibb, EMD Serono, Inivata, Merck and Novartis; and research support from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Genentech, GI Therapeutics, Merck, Novartis, Pfizer and Ludwig Institute of Cancer Research. JK Salama reports research support to institution by Abbvie; and support to institution of spouse by Bristol Myers Squibb, Genentech, Immunocore and Merck. L Raez reports research support to institution from Bristol Myers Squibb, Genentech/Roche, Pfizer, Nanthealth, MSD, Merck Serono, Lilly Oncology, Boehringer Ingelheim, Syndax, Novartis, Heat Biologics, AstraZeneca, Exosomes DX, Liquid Genomics and Loxo Oncology. A Ganti reports honoraria for consulting from Genentech, AstraZeneca and Flagship Biosciences; honoraria for advisory board from Genentech, AstraZeneca, G1 Therapeutics and Jazz Pharmaceuticals; DSMC for Y-mAbs Therapeutics; and research support to institution from Merck, NEKTAR, Takeda, AstraZeneca and TAB Biosciences. J Bradley reports honoraria for consulting from Varian, Inc. and Genentech; and scientific advisory board from Mevion Medical systems, Inc. SS Ramalingam reports honoraria for consulting from Amgen, Bristol Myers Squibb, Genentech/Roche, Merck, AstraZeneca, Takeda, Eisai, Daiichi Sankyo, Sanofi, GlaxoSmithKline and Eli Lilly; and grants from Tesaro, Merck, AstraZeneca, Advaxis, Bristo Myers Squibb, Amgen, Takeda, Genmab and GlaxoSmithKline. TE Stinchcombe reports honoraria for consulting from Takeda, AstraZeneca, Genentech/Roche, Foundation Medicine, Pfizer, EMD Serono, Novartis, Daiichi Sankyo, Lilly, Medtronic, Puma Biotechnology, Janssen Oncology and Regeneron; and research funding to institution by Genentech/Roche, Blueprint Medicines, AstraZeneca, Takeda, Advaxis and Regeneron. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.. Schema of the ACCIO trial…
Figure 1.. Schema of the ACCIO trial including three arms.
Pembrolizumab dosing is every 6 weeks. Sequential and concurrent arms each include about 1 year of pembrolizumab. PORT: Postoperative radiation therapy.

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Source: PubMed

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