2022 World Conference on Lung Cancer (ePosters)-EP02.04-007. Phase 2 Trial of Neoadjuvant KRASG12C Directed Therapy with Adagrasib (MRTX849) With or Without Nivolumab in Resectable NSCLC (Neo-KAN)

EP02.04-007. Phase 2 Trial of Neoadjuvant KRASG12C Directed Therapy with Adagrasib (MRTX849) With or Without Nivolumab in Resectable NSCLC (Neo-KAN)

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The Phase 2 trial, known as Neo-KAN, aims to assess the safety and efficacy of neoadjuvant KRASG12C directed therapy with adagrasib (MRTX849) with or without nivolumab in resectable non-small cell lung cancer (NSCLC) patients. Despite standard systemic therapies, 50% of these patients relapse after surgery. Adagrasib is a KRASG12C inhibitor that has shown promising results in advanced NSCLC, with a 43% objective response rate and 80% disease control rate. Additionally, adagrasib has been shown to recondition the tumor microenvironment to enhance anti-tumor immune activity, making it a potential candidate for combination therapy with anti-PD-1. <br /><br />The study design involves a prospective, open-label, phase 2 trial conducted at 12 sites across North America. The trial will enroll 42 patients, with 21 in each cohort. Cohort A will receive adagrasib alone, while cohort B will receive adagrasib in combination with nivolumab. The neoadjuvant regimen will last for 42 days, and surgery will be performed within two weeks of its completion. The post-operative systemic therapy will be determined by the treating oncologist.<br /><br />The primary endpoint is the pathological complete response (pCR) rate in each arm, which will be assessed by examining surgical resection specimens for the absence of residual viable tumor. The secondary endpoint is the major pathologic response (MPR) rate, defined as 10% residual viable tumor. The study aims to evaluate whether the pCR rates with adagrasib-based therapy exceed the predicted response rate with chemotherapy.<br /><br />The trial will also include correlative analyses to evaluate the genomic and immunologic features of response and resistance to treatment. This will involve comprehensive evaluations using whole exome sequencing, multiplex immunohistochemistry, TCR sequencing, and plasma circulating tumor DNA analysis.<br /><br />The trial is funded by Mirati Therapeutics and Bristol Myers Squibb, with additional support from the ASCO Women Who Conquer Cancer Women Leaders in Oncology Young Investigators Award.

Asset Subtitle

Patrick M Forde

Meta Tag

Speaker Patrick M Forde

Topic Early Stage Non-small Cell Lung Cancer - Systemic Therapy

Keywords

Neo-KAN

neoadjuvant therapy

adagrasib

MRTX849

nivolumab

non-small cell lung cancer

surgery

pCR rate

chemotherapy

genomic features