A Phase II Study of Neoadjuvant Sotorasib in Combination With Cisplatin or Carboplatin and Pemetrexed for Surgically Resectable Stage IIA-IIIB Non-Squamous Non-Small Cell Lung Cancer With a KRAS p.G12C Mutation

Lung Cancer Clinical Trial

Official title: A Phase II Study of Neoadjuvant Sotorasib in Combination With Cisplatin or Carboplatin and Pemetrexed for Surgically Resectable Stage IIA-IIIB Non-Squamous Non-Small Cell Lung Cancer With a KRAS p.G12C Mutation

Status Recruiting

Clinical Trial Summary

This is a phase II, single-arm, open-label study evaluating the efficacy, safety and tolerability of neoadjuvant sotorasib in combination with cisplatin (or carboplatin) and pemetrexed chemotherapy for patients with surgically resectable stage IIA - IIIB (T3-T4/N2) (based on AJCC 8th edition), non-squamous NSCLC with a KRAS p.G12C mutation. The primary objective of the study is to determine whether neoadjuvant therapy with 4 cycles of at least one dose of sotorasib plus cisplatin (or carboplatin) and pemetrexed can be administered safely and result in improved MPR rate in patients with KRAS p.G12C-mutant non-squamous NSCLC compared with the historical control MPR rate for platinum-based chemotherapy alone.

Clinical Trial Description

Objectives

Primary:

• To evaluate the efficacy of induction with sotorasib (AMG 510) in combination with cisplatin (or carboplatin) and pemetrexed in patients with surgically resectable KRAS p.G12C-mutant non-squamous NSCLC as assessed by major pathologic response rate in resected tumor specimens.

• To determine the safety, tolerability and RP2D of sotorasib in combination with cisplatin (or carboplatin) and pemetrexed as induction therapy in patients with surgically resectable KRAS p.G12C-mutant nonsquamous NSCLC

Secondary:

• To evaluate the efficacy of induction sotorasib in combination with cisplatin (or carboplatin) and pemetrexed in patients with surgically resectable KRAS p.G12C mutant non-squamous NSCLC as assessed by : Objective response rate (ORR), Eventfree survival, Recurrence-free survival, Overall Survival (OS), Complete Resection (R0) and Pathologic complete response rate (pCR)

• To determine the safety and tolerability of sotorasib in combination with cisplatin (or carboplatin) and pemetrexed as induction therapy in patients with surgically resectable KRAS p.G12C-mutant nonsquamous NSCLC.

Exploratory:

• To evaluate biomarkers of response to induction sotorasib in combination with cisplatin (or carboplatin) and pemetrexed in surgically resectable KRAS p.G12C-mutant non-squamous NSCLC.

• To assess modulation of tissue and/or blood markers in response to induction with sotorasib in combination with cisplatin (or carboplatin) and pemetrexed in surgically resectable KRAS p.G12C-mutant nonsquamous NSCLC.

• To evaluate mechanisms of adaptation and/or resistance to sotorasib in combination with cisplatin (or carboplatin) and pemetrexed in surgically resectable KRAS p.G12C-mutant non-squamous NSCLC.

• To evaluate immune modulation in tissue and the periphery in response to induction sotorasib in combination with cisplatin (or carboplatin) and pemetrexed in surgically resectable KRAS p.G12C-mutant nonsquamous NSCLC. ;

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

• NCT number: NCT05118854
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Contact: Ferdinandos Skoulidis
• Phone: (713) 792-6363
• Email: fskoulidis@mdanderson.org
• Status: Recruiting
• Phase: Phase 2
• Start date: March 30, 2022
• Completion date: October 20, 2025