A Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of Sotorasib Plus Trastuzumab Deruxtecan in Patients With Advanced Non-Small Cell Lung Cancer With a KRASG12C Mutation

Official Summary

This phase I/II trial tests the safety, side effects and best dose of sotorasib with trastuzumab deruxtecan and how well the combination works in treating patients with KRAS G12C mutated non-small cell lung cancer that has spread to nearby tissues or lymph nodes (locally advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sotorasib blocks a protein made by the mutated KRAS gene (KRAS p.G12C), which may help keep tumor cells from growing and may kill them. It is a type of targeted therapy. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving sotorasib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or effective in treating patients with locally advanced or metastatic non-small cell lung cancer with a KRAS G12C mutation.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 37 participants

Interventions

• PROCEDURE: Biopsy Procedure — Undergo tumor biopsy
• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT
• PROCEDURE: Echocardiography Test — Undergo ECHO
• PROCEDURE: Magnetic Resonance Imaging — Undergo MRI

Primary Outcomes

• Dose-limiting toxicities of combined trastuzumab deruxtecan (DS-8201a) and sotorasib (AMG-510) treatment (Phase I) (Within the first 21 days of treatment initiation)
• Overall response rate (ORR) (Phase II) (Up to 5 years)

Secondary Outcomes

• Maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of trastuzumab deruxtecan (DS-8201a) and sotorasib (AMG-510) combination (Phase I) (Up to 5 years)
• ORR (Phase I) (Up to 5 years)
• Progression-free survival (PFS) (Phase II) (From start of treatment to disease progression or death due to any cause, assessed up to 5 years)
• Duration of response (Phase II) (From the time measurement criteria are first met for complete response or partial response until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years)
• Overall survival (OS) (Phase II) (From first treatment to time of death due to any cause, assessed up to 5 years)

Trial Locations

• Moffitt Cancer Center-International Plaza, Tampa, Florida, United States
• Moffitt Cancer Center - McKinley Campus, Tampa, Florida, United States
• Moffitt Cancer Center, Tampa, Florida, United States
• Moffitt Cancer Center at Wesley Chapel, Wesley Chapel, Florida, United States

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