Phase 1/2 Study of the Safety and Tolerability of Nivolumab Plus Crizotinib for the First-Line Treatment of Anaplastic Lymphoma Kinase Translocation — Positive Advanced Non–Small Cell Lung Cancer (CheckMate 370)
Open accessAbstract
Introduction Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses. Herein we report data from a study assessing nivolumab plus crizotinib in patients with previously untreated advanced ALK translocation-positive NSCLC.Methods Group E in CheckMate 370 was a single-arm cohort designed to evaluate the safety of first-line nivolumab (240 mg every 2 weeks) plus crizotinib (250 mg twice daily) in patients with ALK translocation-positive NSCLC. The primary endpoint of safety would be met if ≤20% of patients discontinued treatment due to treatment-related adverse events by week 17. Objective response rate was a secondary endpoint. A planned safety review occurred in November 2016; the data cutoff was May 26, 2017.Results Of the first 13 patients treated with nivolumab plus crizotinib, 5 (38%) developed severe hepatic toxicities leading to the discontinuation of the combination. Of these, two patients died and the presence of severe hepatic toxicities may have contributed to death. Enrollment was closed and combination treatment discontinued due to observed grade ≥3 hepatic toxicities. Five patients (38%) had a partial response.Conclusions These findings do not support further evaluation of nivolumab 240 mg every 2 weeks plus crizotinib 250 mg twice daily.
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ALK-TKI combined with α-PD-1/PD-L1 might increase treatment-associated hepatotoxicity.
“It should be noted that ALK-TKI combined with α-PD-1/PD-L1 might increase treatment-associated hepatotoxicity.”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [203]
In the phase 1/2 study CheckMate-370, 38% of patients receiving nivolumab plus crizotinib developed severe hepatic toxicities, leading to termination of enrollment.
“In the phase 1/2 study CheckMate-370, 38% of patients receiving nivolumab plus crizotinib developed severe hepatic toxicities, leading to the termination of the enrollment [203].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [203]
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New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., Dancey, J., Arbuck, S., Gwyther, S., Mooney, M., et al. (2009) · European Journal of Cancer · doi:10.1016/j.ejca.2008.10.026 · Cited by 29,534 · see citing works
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · see citing works
Self-citationNivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447 · see citing works
Self-citationIdentification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer
Soda, M., Choi, Y. L., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S.-I., Watanabe, H., Kurashina, K., Hatanaka, H., et al. (2007) · Nature · doi:10.1038/nature05945 · Cited by 5,439 · see citing works
First-Line Crizotinib versus Chemotherapy in <i>ALK</i> -Positive Lung Cancer
Solomon, B. J., Mok, T., Kim, D.-W., Wu, Y.-L., Nakagawa, K., Mekhail, T., Felip, E., Cappuzzo, F., Paolini, J., Usari, T., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408440 · Cited by 3,190 · see citing works
First-Line Nivolumab in Stage IV or Recurrent Non–Small-Cell Lung Cancer
Carbone, D. P., Reck, M., Paz-Ares, L., Creelan, B., Horn, L., Steins, M., Felip, E., van den Heuvel, M. M., Ciuleanu, T.-E., Badin, F., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1613493 · Cited by 2,503 · see citing works
Self-citationGlobal Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer
Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.11.025 · Cited by 2,317 · see citing works
Horn, L., Spigel, D. R., Vokes, E. E., Holgado, E., Ready, N., Steins, M. B., Poddubskaya, E. V., Borghaei, H., Felip, E., Paz-Ares, L. G., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.3062 · Cited by 861 · see citing works
Self-citationBlackhall, F. H., Peters, S., Bubendorf, L., Dafni, U. G., Kerr, K. M., Hager, H., Soltermann, A., O'Byrne, K. J., Dooms, C., Sejda, A., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.54.5921 · Cited by 195 · see citing works
Felip, E., de Braud, F., Maur, M., Loong, H. H.-F., Shaw, A. T., Vansteenkiste, J., John, T., Liu, G., Lolkema, M. P., Scott, J. W., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.2502 · Cited by 37 · see citing works
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Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works
Crizotinib-induced immunogenic cell death in non-small cell lung cancer
Liu, P., Zhao, L., Pol, J., Levesque, S., Petrazzuolo, A., Pfirschke, C., Engblom, C., Rickelt, S., Yamazaki, T., Iribarren, K., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09415-3 · Cited by 302 · see citing works
Lin, J. J., Chin, E., Yeap, B. Y., Ferris, L. A., Kamesan, V., Lennes, I. T., Sequist, L. V., Heist, R. S., Mino-Kenudson, M., Gainor, J. F., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.09.001 · Cited by 140 · see citing works
- Authors
- Spigel, D. R., Reynolds, C., Waterhouse, D., Garon, E. B., Chandler, J., Babu, S., Thurmes, P., Spira, A., Jotte, R., Zhu, J., Lin, W. H., & Blumenschein, G.
- Affiliations
- Sarah Cannon (US)
- Oncology Specialists of Charlotte (US)
- The US Oncology Network (US)
- University of California, Los Angeles (US)
- West Cancer Center (US)
- Fort Wayne Medical Institute (US)
- Minnesota Oncology (US)
- Virginia Cancer Specialists (US)
- Rocky Mountain Cancer Centers (US)
- Bristol-Myers Squibb (United States) (US)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Spigel, David R.
- ORCID
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 13
- Issue
- 5
- Pages
- 682-688
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W2791886669
- Cited by
- 229
- References
- 10
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 17 · 2023: 24 · 2022: 34 · 2021: 32 · 2020: 44 · 2019: 26 · 2018: 26 · 2015: 1
- FWCI
- 24.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- nivolumab, crizotinib, anaplastic lymphoma kinase, ALK rearrangement, non-small cell lung cancer, first-line therapy, immune checkpoint inhibitors, combination therapy, hepatotoxicity, treatment safety, objective response rate
- MeSH terms
- Antineoplastic Agents, Immunological, Crizotinib, Anaplastic Lymphoma Kinase, Nivolumab, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Translocation, Genetic
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