KRAS mutations occur in approximately 30% of lung adenocarcinomas, mainly in codon 12 (83% of cases), p.G12C being the prevalent one (40%), followed by p.G12V and p.G12D (22 and 16%, respectively). Treatment options for advanced KRAS mutant non-small-cell lung cancer (KRAS-MT NSCLC) are limited to chemotherapy and immune checkpoint inhibitors (CPIs). However, clinical trials exploring specific targeted agents are expected to change the treatment landscape of this disease. Here, we describe the design and scientific rationale of the randomized, phase II, open label, RAMP-202 study, which will evaluate the efficacy and safety of VS-6766 versus VS-6766 in combination with defactinib in advanced KRAS-MT NSCLC patients after failure of prior platinum-based chemotherapy and CPI.

Plain language summary

The alteration of KRAS gene occurs in approximately 30% of lung cancers. According to international guidelines, treatment options for patients with advanced KRAS mutant lung cancer are now limited to chemotherapy and immunotherapy. However, clinical trials are exploring how specific targeted agents are expected to change the treatment landscape of this disease. Here, we describe the design and scientific rationale of the RAMP-202 study, which will evaluate the efficacy and safety of two new biological agents for patients with KRAS mutant lung cancer. The enrolled patients were those who had failure of prior platinum-based chemotherapy and immunotherapy.

Clinical Trial Registration: NCT04620330 (ClinicalTrials.gov).

Keywords:

Papers of special note have been highlighted as: •• of considerable interest

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Vol. 18, No. 16

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History

Received 10 December 2021

Accepted 22 February 2022

Published online 14 March 2022

Published in print May 2022

Information

Keywords

Author contributions

All co-authors have contributed equally to this article, in regard to the conception of the work, the writing and the final approval of the entire document.

Acknowledgments

The authors thank the patients and their families and caregivers, as well as all investigators and site personnel, for participating in this trial.

Financial & competing interests disclosure

L Denis and A Koustenis are is employees and stock ownerships of Verastem Oncology. A Koustenis is also stock ownership of Eli Lilly and Company. S Novello is advisor and speaker bureau for AstraZeneca, Boehringer Ingelheim, BeiGene, Amgen, Eli Lilly and Company, Roche, MSD, Takeda Pharmaceutical, Pfizer, Sanofi Aventis, Novartis and Janssen Pharmaceutical. 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.

Ethical conduct of research

The authors attest that the study protocol was approved by the appropriate ethics committee or institutional review board at each participating center. The study was conducted in accordance with standards of Good Clinical Practice and the Declaration of Helsinki. All participants will provide written informed consent before enrollment.

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