Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation

Conditions

• Locally Advanced Lung Non-Small Cell Carcinoma
• Metastatic Lung Non-Small Cell Carcinoma
• Stage III Lung Cancer AJCC v8
• Stage IV Lung Cancer AJCC v8

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo tumor biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Computed Tomography — PROCEDURE
  Undergo CT
• Echocardiography Test — PROCEDURE
  Undergo ECHO
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Multigated Acquisition Scan — PROCEDURE
  Undergo MUGA
• Sotorasib — DRUG
  Given PO
• Trastuzumab Deruxtecan — BIOLOGICAL
  Given IV

Study Details

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.

Key Dates

Start date

Aug 7, 2026

Status verified

Apr 2026

Primary completion

Jun 14, 2027

Completion

Jun 14, 2027

Study Design

Enrollment

37 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Treatment (trastuzumab deruxtecan, sotorasib)
  Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 and sotorasib PO QD on days 1-21 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy and brain MRI at screening and ECHO or MUGA, CT, MRI and blood sample collection throughout the study. Additionally, patients with brain metastasis undergo brain MRI throughout the study.

Primary Outcome Measure

Dose-limiting toxicities of combined trastuzumab deruxtecan (DS-8201a) and sotorasib (AMG-510) treatment (Phase I) [ Time Frame: Within the first 21 days of treatment initiation ]

Locations (9)

Find similar trials in Sacramento, CA

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