2023 World Conference on Lung Cancer (Posters)-P2.11. A Phase 1B Trial of Tarloxotinib and Sotorasib in Lung Cancer Patients with KRAS G12C Mutations

P2.11. A Phase 1B Trial of Tarloxotinib and Sotorasib in Lung Cancer Patients with KRAS G12C Mutations - PDF(Slides)

Pdf Summary

This Phase 1b trial investigates the combination of Tarloxotinib and Sotorasib in lung cancer patients with KRAS G12C mutations. KRAS G12C mutations are found in 15% of patients with lung adenocarcinoma, and Sotorasib is the first FDA-approved KRAS G12C inhibitor. However, most patients with this mutation do not respond well to therapy and have a high rate of relapse. The combination of Tarloxotinib and Sotorasib has the potential to overcome resistance mechanisms with minimal toxicity.<br /><br />The study design involves a 3x3 dose de-escalation design dependent on dose-limiting toxicities (DLTs). The primary endpoints of the study are determining safety and tolerability, as well as objective response rate (ORR) assessed by RECIST 1.1 criteria. Secondary endpoints include duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).<br /><br />The study includes patients with histologically confirmed non-small cell lung cancer (NSCLC) with KRAS G12C mutations who have previously received platinum-containing chemotherapy and at least one month of a KRAS G12C inhibitor with disease progression. Brain metastases must be treated and inactive, and patients must have measurable disease. There are specific exclusion criteria, such as NYHA Class 3 congestive heart failure and QTc480 ms or a history of Long Qt syndrome.<br /><br />The study is divided into two stages: a safety lead-in stage with six patients and an efficacy stage with twelve patients. Treatment cycles consist of Sotorasib and Tarloxotinib administered on specific days of a 28-day cycle. Tumor assessments are done every 8 weeks.<br /><br />The authors acknowledge financial support from Rain Oncology, Inc., and provide contact information for correspondence. The study schema, key inclusion/exclusion criteria, and references are also provided. A diagram of the KRAS signaling pathway is included to illustrate the potential impact of the combination therapy.

Asset Subtitle

Mariam Alexander

Meta Tag

Speaker Mariam Alexander

Topic Metastatic NSCLC: Targeted Therapy - KRAS/MET

Keywords

Phase 1b trial

Tarloxotinib

Sotorasib

lung cancer

KRAS G12C mutations

FDA-approved

inhibitor

therapy

safety

tolerability