Recruiting

Sotorasib Plus Trastuzumab Deruxtecan for Advanced KRASG12C Mutated Non-Small Cell Lung Cancer

What is being tested

Biopsy Procedure

+ Biospecimen Collection

+ Computed Tomography

ProcedureDrugBiological

Who is being recruted

Bronchial Neoplasms+7

+ Carcinoma, Bronchogenic

+ Carcinoma, Non-Small-Cell Lung

Over 18 Years

+54 Eligibility Criteria

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 1 & 2

Interventional

Study Start: August 2026

See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)

Last updated: March 25, 2026

Sourced from a government-validated database.Claim as a partner

Study start date: August 7, 2026

Actual date on which the first participant was enrolled.

This clinical trial is exploring the safety, tolerability, and effectiveness of two medications, Sotorasib and Trastuzumab Deruxtecan, in treating advanced Non-Small Cell Lung Cancer with a specific genetic mutation known as KRASG12C. The study is designed for patients who have previously undergone treatment with a KRASG12C inhibitor and platinum-based chemotherapy, with or without certain immunotherapies. The primary goal is to find a safe dosage combination that works well for these patients and to measure the overall response rate to the treatment. This research is important as it aims to provide a new treatment option for patients with this specific type of lung cancer, potentially improving their care and quality of life. During the trial, participants will receive Trastuzumab Deruxtecan intravenously on day 1 and Sotorasib orally once daily from days 1 to 21 of each cycle. Each cycle lasts 21 days and will continue unless the disease progresses or unacceptable side effects occur. Throughout the study, patients will undergo various tests, including tumor biopsy, brain MRI, ECHO or MUGA, CT, MRI, and blood sample collection. The study will monitor the side effects associated with the combination treatment and assess the response to the therapy. After the completion of the treatment, patients will be followed up every 3 months for up to 5 years.

Official TitleA 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

NCT07012031

Principal SponsorNational Cancer Institute (NCI)

Last updated: March 25, 2026

Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

37 patients to be enrolled

Total number of participants that the clinical trial aims to recruit.

Treatment Study

These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.

Conditions

Criteria

Any sex

Biological sex of participants that are eligible to enroll.

Over 18 Years

Range of ages for which participants are eligible to join.

Healthy volunteers not allowed

If individuals who are healthy and do not have the condition being studied can participate.

Conditions

Pathology

Bronchial NeoplasmsCarcinoma, BronchogenicCarcinoma, Non-Small-Cell LungLung DiseasesLung NeoplasmsNeoplasmsNeoplasms by SiteRespiratory Tract DiseasesRespiratory Tract NeoplasmsThoracic Neoplasms

Criteria

32 inclusion criteria required to participate

Data must be available on the date patients received the last dose of KRAS^G12C inhibitor and the date of disease progression on their last treatment prior to screening for this trial. Data must be available on the last treatment they received and if it was not or did not include a KRAS^G12C inhibitor. The time between last KRAS^G12C inhibitor and treatment on this trial will be collected prior to enrollment

Patients must have histologically or cytologically documented locally advanced or metastatic KRAS^G12C-mutant NSCLC that has previously been treated with a KRAS^G12C inhibitor AND an immune checkpoint inhibitor (ICI) AND chemotherapy, either given concurrently or sequentially, UNLESS they have any contra-indications to any drug class described above

Patients must have KRAS^G12C mutation identified by tumor tissue or plasma circulating tumor deoxyribonucleic acid (ctDNA) profiling using a Clinical Laboratory Improvement Act (CLIA) certified College of American Pathologists (CAP) accredited platform; local molecular testing will be allowed. Testing must have been done within the last 5 years before enrollment in this study

Data must be available for which prior KRAS^G12C inhibitor treatment the patient has received and the dates that they received it (type of KRAS^G12C inhibitor used and start and end dates must be collected prior to enrollment)

Show More Criteria

22 exclusion criteria prevent from participating

Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous or interfere with the evaluation of the clinical study results

Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, has current ILD, or where suspected ILD cannot be ruled out by imaging at screening. These patients will be excluded because trastuzumab deruxtecan (DS-8201a) is known to increase the risk of developing ILD and pneumonitis

Patients with clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, prior complete pneumonectomy), and any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis, etc.) where there is documented or a suspicion of pulmonary involvement or pneumonectomy at the time of screening. These patients will be excluded because trastuzumab deruxtecan (DS-8201a) is known to increase the risk of developing ILD and pneumonitis

Patients who have had chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic body radiation therapy). These patients will be excluded because trastuzumab deruxtecan (DS-8201a) and sotorasib (AMG-510) are known to increase the risk of developing pneumonitis

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.

Treatment Groups

Study Objectives

One single intervention group is designated in this study

This study does not include a placebo group

Treatment Groups

Group I

Experimental

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.

Study Objectives

Primary Objectives

Secondary Objectives

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.

This study has 4 locations

Recruiting

Moffitt Cancer Center-International Plaza

Tampa, United StatesOpen Moffitt Cancer Center-International Plaza in Google Maps

Recruiting

Moffitt Cancer Center - McKinley Campus

Tampa, United States

Recruiting

Moffitt Cancer Center

Tampa, United States

Recruiting

Moffitt Cancer Center at Wesley Chapel

Wesley Chapel, United States

Recruiting

4 Study Centers