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
Procedure
Drug
Biological
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, 2026Actual 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 enrolledTotal 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.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Bronchial Neoplasms
Carcinoma, Bronchogenic
Carcinoma, Non-Small-Cell Lung
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic 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.

Show More Criteria

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.

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.

Undergo tumor biopsy

Undergo blood sample collection

Undergo CT

Undergo ECHO

Undergo MRI

Undergo MUGA

Given PO

Given IV
Study Objectives
Primary Objectives

Will be defined as the proportion of patients with a confirmed response as per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. Will be plotted using Kaplan-Meier method.

Will be defined as an adverse event (AE) that is at least possibly related to the study treatment. Severity will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Secondary Objectives

Will be defined as the proportion of patients with a confirmed response (i.e., response confirmed by a second radiographic evaluation) as per investigator assessment according to RECIST v 1.1. Will be summarized using both a point estimate and its exact 95% confidence interval based on the binomial distribution.

Will be plotted using Kaplan-Meier method.

Will be plotted using Kaplan-Meier method.

Will be plotted using Kaplan-Meier method.

Will be tabulated by grade. AEs will be described and graded using NCI CTCAE v 5.0.

Gene expression levels will be measured by counts (i.e., by the number of reads mapped on each gene). Data analysis will be descriptive statistics in nature (e.g., proportion of ERBB2/ERBB3 gene expression in each response group).

Will be measured by ribonucleic acid (RNA)-Sequencing.

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 LAOToronto, CanadaSee the location
Recruiting
One Study Center
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