Recruiting

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

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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
+53 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: January 27, 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 focused on understanding the safety and effectiveness of combining two drugs, sotorasib and trastuzumab deruxtecan, for patients with advanced non-small cell lung cancer that has a specific genetic change known as the KRASG12C mutation. This study is important because patients who have this type of cancer and have already tried other treatments, like KRASG12C inhibitors and chemotherapy with or without certain immune therapies, need more effective options. By testing these drugs together, researchers hope to find a new way to help these patients by seeing how well the drugs can reduce cancer size or slow its growth. In the study, participants receive trastuzumab deruxtecan through an IV infusion, which is like a drip, once every 21 days. They also take sotorasib in pill form daily. The study tracks how the cancer responds using scans, biopsies, and other tests to see if the cancer shrinks or stops growing. There are also regular checks for safety to find out the best dose of the drug combination that patients can tolerate. The study involves monitoring side effects and how long any positive effects last. Participants are followed up for several years to gather long-term data on survival and any ongoing effects of the treatment.

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: January 27, 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

30 inclusion criteria required to participate
Creatinine ≤ 1.5 x institutional ULN OR creatinine clearance (CrCL) ≥ 30 mL/min/ as determined by (using actual body weight) (within 14 days of enrollment).
Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (within 14 days of enrollment).
Male subjects must not freeze or donate sperm starting at screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study.
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23 exclusion criteria prevent from participating
Patients with spinal cord compression, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms.
Patients who have had prior treatment with an antibody drug conjugate with a topoisomerase 1 inhibitor payload (i.e., sacituzumab govitecan, datopotomab deruxtecan, or trastuzumab deruxtecan) or with a topoisomerase inhibitor.
Patients that have received a live vaccine within 30 days prior to the first dose of study drug will be excluded. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, bacillus Calmette- Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Patients with an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
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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 1 location

Recruiting

University Health Network Princess Margaret Cancer Center LAO

Toronto, CanadaSee the location
Recruiting
One Study Center