Actively Recruiting
Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
37
Participants Needed
9
Research Sites
44 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
Sotorasib in Combination With Trastuzumab Deruxtecan for the Treatment of Locally Advanced and Metastatic Non-small Cell Lung Cancer With a KRAS G12C Mutation
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients have locally advanced or metastatic KRAS G12C-mutant NSCLC previously treated with KRAS G12C inhibitor, immune checkpoint inhibitor, and chemotherapy, unless contraindicated
- KRAS G12C mutation confirmed by tumor tissue or plasma ctDNA within 5 years
- Available data on prior KRAS G12C inhibitor treatment and progression
- Available HER2 immunohistochemistry and ERBB2 mutation status by molecular testing
- Measurable disease by RECIST v1.1 on CT or MRI
- Age 18 years or older
- ECOG performance status 0 to 2
- Hemoglobin ≥ 9 g/dL, leukocytes ≥ 3000/mcL, absolute neutrophil count ≥ 1500/mcL
- No granulocyte colony stimulating factor within 1 week prior to screening
- Platelets ≥ 100,000/mcL, no recent transfusions within 1 week prior to screening
- Total bilirubin ≤ 1.5 x ULN (≤ 3 x ULN with Gilbert's syndrome or liver metastases)
- AST/ALT ≤ 3 x ULN (≤ 5 x ULN with liver metastases)
- Serum albumin ≥ 2.5 g/dL
- INR/PT and aPTT ≤ 1.5 x ULN
- Creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 30 mL/min
- Left ventricular ejection fraction ≥ 50% by ECHO or MUGA within 28 days
- HIV patients on effective therapy with undetectable viral load eligible
- Hepatitis B patients with undetectable viral load on suppressive therapy eligible
- Hepatitis C patients treated and cured or on treatment with undetectable viral load eligible
- Patients with treated brain metastases with specified washout periods eligible
- Patients with new or progressive brain metastases eligible if CNS treatment not immediately required
- Life expectancy ≥ 12 weeks
- Corrected QT interval ≤ 470 msec for women and ≤ 450 msec for men
- Willingness to undergo mandatory pre-treatment biopsy (optional in phase I)
- Ability to ingest and retain oral medications
- Women of child-bearing potential must use dual contraception and have negative pregnancy test
- Men and women must agree to effective contraception or abstinence during and after study
- Male subjects must not donate sperm during and 4 months after study
- Female subjects must not donate or retrieve ova during and 7 months after study
- Ability to understand and sign informed consent
You will not qualify if you...
- History or current interstitial lung disease requiring steroids or suspected ILD
- Severe pulmonary compromise from lung disorders or autoimmune diseases involving lungs
- Chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic body radiation)
- Recent major surgery with unhealed incisions
- Prior treatment with antibody drug conjugates with topoisomerase 1 inhibitors or topoisomerase inhibitors
- Significant lung disease requiring systemic corticosteroids >10 mg prednisone daily in last 6 months
- Clinically significant corneal disease
- Untreated or symptomatic spinal cord compression
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Unrecovered adverse events from prior cancer therapy except alopecia
- Receiving other investigational agents
- History of allergic reactions to sotorasib, trastuzumab deruxtecan, or similar compounds
- History of severe hypersensitivity to monoclonal antibodies
- Taking strong CYP3A4 inducers without alternative
- Use of P-glycoprotein substrates with serious toxicity risk without dose adjustment
- Uncontrolled illness or condition making study participation hazardous or interfering with evaluation
- Pregnant or breastfeeding women
- Uncontrolled or significant cardiovascular disease
- Prior pneumonitis grade 2 or higher or interstitial lung disease
- Inability to receive iodinated or gadolinium contrast for scans
- Pleural, pericardial, or ascitic effusions requiring drainage within 2 weeks
- Live vaccine within 30 days prior to first dose (except killed influenza vaccines)
AI-Screening
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Trial Site Locations
Total: 9 locations
1
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Actively Recruiting
2
Moffitt Cancer Center-International Plaza
Tampa, Florida, United States, 33607
Actively Recruiting
3
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, United States, 33612
Actively Recruiting
4
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Actively Recruiting
5
Moffitt Cancer Center at Wesley Chapel
Wesley Chapel, Florida, United States, 33544
Actively Recruiting
6
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Actively Recruiting
7
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210
Actively Recruiting
8
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
9
University of Virginia Cancer Center
Charlottesville, Virginia, United States, 22908
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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