Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer EGFR Exon 20 insertion mutations after platinum-based chemotherapy

Abstract

Background

In the single-arm CHRYSALIS trial, advanced non-small cell lung cancer patients harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon 20ins) showed durable responses to amivantamab, an EGFR-MET bispecific antibody targeting tumors with EGFR Exon 20ins. This study compared the effectiveness of amivantamab to real-world systemic anti-cancer therapies in Japan.

Patients and methods

External control patients were selected by applying CHRYSALIS eligibility to Japanese patients from LC-SCRUM-Asia. External control patients were included for every qualifying line of therapy after platinum-based chemotherapy. Propensity score weighting was applied to external control patients to adjust for differences in baseline characteristics. Outcomes were compared between external control patients, and all and Asian-only CHRYSALIS patients using weighted Cox proportional hazards regression models for progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS), and generalized estimating equations with repeated measurements for overall response rate (ORR).

Results

One hundred fifteen CHRYSALIS and 94 external control patients were identified. Compared to external control patients, amivantamab-treated patients had significantly longer OS (median OS 19.88 vs 14.09 months, HR [95% CI] 0.59 [0.40–0.88]), PFS (median PFS 6.74 vs 4.73 months, HR 0.59 [0.45–0.78]), TTNT (median TTNT 12.16 vs 5.09 months, HR 0.39 [0.29–0.53]), and significantly higher ORR (41.7% vs 14.1%). Analyses of amivantamab-treated Asian patients (n = 61) showed similar clinical benefits.

Conclusion

In the absence of clinical evidence from randomized clinical trials, this study reflects the benefit of amivantamab after platinum-based chemotherapy for advanced non-small cell lung cancer patients harboring EGFR Exon 20ins, compared to current real-world therapies.

Keywords:

• CHRYSALIS trial
• external control
• LC-SCRUM-Asia
• amivantamab
• EGFR exon 20 insertions

Acknowledgements

The authors would like to thank the patients, their families, collaborators in 183 institutions as well as collaborating pharmaceutical companies for their participation in LC-SCRUM-Asia. LC-SCRUM-Asia's collaborating pharmaceutical companies are Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Janssen, Kyowa Kirin, Medical & Biological Laboratories, Merck Serono, Merus, MSD, Novartis, Ono, Pfizer, Sumitomo Dainippon, Taiho, and Takeda.

Disclosure statement

T. M. Kim received honoraria from or held an advisory role at AstraZeneca, Boryung, F. Hoffman-La Roche Ltd/Genentech, Inc, IMDBx, Inc., Janssen, Novartis, Regeneron, Samsung Bioepis, Sanofi, Takeda, Yuhan, and received research funding from AstraZeneca-Korea Health Industry Development Institute, outside of the submitted work.

N. Girard received honoraria and/or consulting fees from AbbVie, Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Daachi, Janssen, Lilly, Mirati, MSD, Novartis, Novartis, Pfizer, Roche, Sanofi, Takeda, and received grants from MSD and AstraZeneca paid to institution outside of the submitted work.

Zhuo, D. Y. Yu, Y. Yang, and M. Murota are full-time employees of Janssen. J. Zhuo received long-term incentives from Janssen. G. K. M. Low was a full-time employee of Janssen when this study was performed and received long-term incentives from Janssen. She is not an employee of Janssen currently.

C.T.K. Lim and N. J. Kleinman are full-time employees of IQVIA.

C. Cho is the founder of DAAN Biotherapeutics, has stock ownership in Bridgebio Therapeutics, Cyrus Therapeutics, Gencurix Inc, Interpark Bio Convergence, J INTS Bio, Kanaph Therapeutic Inc, TheraCanVac Inc, received consulting fees and/or research funding from Abion, AbbVie, AstraZeneca, Bayer, BeiGene, Blueprint Medicines, Boehringer-Ingelheim, BMS, Bridgebio Therapeutics, CHA Bundang Medical Center, Champions Oncology, CJ, CJ Bioscience, CJ Blossom Park, CureLogen, Cyrus Therapeutics, Dizal Pharma, Dong-A ST, Eli Lilly, Genexine, GI-Cell, GIInovation, Guardant, Hanmi, HK Inno. N, Imnewrun Biosciences Inc., Interpark Bio Convergence Corp, ImmuneOncia, Janssen, JINTSbio, Kanaph Therapeutics, LG Chem, Medpacto, MOGAM Institute, MSD, Novartis, Nuvalent, Oncternal, Onegene Biotechnology, Ono, Oscotec, Pfizer, RandBio, Regeneron, Roche, Takeda, Therapex, Yuhan, and received royalty from Champions Oncology, Crown Bioscience, Imagen, outside of the submitted work.

Data availability statement

Due to the nature of the research and due to ethical/legal/commercial restrictions, supporting data is not available.

Additional information

Funding

This study was sponsored by Janssen Asia Pacific, a division of Johnson & Johnson International (Singapore) Pte. Ltd. It is an affiliate of the Janssen Pharmaceutical Companies of Johnson & Johnson which owns Janssen Biotech, the developer of amivantamab. LCSCRUM-Asia was supported by grants from the Practical Research for Innovation Cancer Control from the Japan Agency for Medical Research and Development (AMED) and funds from SCRUM-Japan. The sponsor designed and conducted the study, analyzed and managed the data. Data were interpreted by the authors and the sponsor. The authors and the sponsor prepared, reviewed, and approved the manuscript, and made the decision to submit the manuscript for publication.