A Phase 2 Basket Trial in Which Patients With Advanced Solid Tumors Carrying the KRAS G12C mUtation Receive Treatment With a Combination of Sotorasib and Panitumumab

August 14, 2023 updated by: Lee, Soo Hyeon, Korea University Anam Hospital

A Phase 2 Basket Trial in Which Patients With Advanced Solid Tumors Carrying the KRAS G12C mUtation Receive Treatment With a Combination of Sotorasib and Panitumumab (KRAUS)

Kirsten rat sarcoma (KRAS) mutation is one of the most common genetic mutations associated with tumor development in various human cancers, including pancreatic cancer, non-small cell lung cancer, and colorectal cancer. Previous studies have shown that KRAS mutations are present in approximately 70% of pancreatic cancer patients, 35% of colorectal cancer patients, 20% of non-small cell lung cancer patients, and 15% of cervical cancer patients. Patients with KRAS mutations generally have a shorter overall survival and increased resistance to treatment compared to wild-type tumors. KRAS mutations have been known for decades, but they have been considered "undruggable" as effective therapies targeting them were lacking.

Preclinical studies focusing on colorectal and non-small cell lung cancer cell lines have suggested that colorectal cancer cell lines exhibit a stronger response to EGFR signaling and activation of multiple RTKs (Receptor Tyrosine Kinases) than non-small cell lung cancer cell lines. As a result, they show poorer responses to KRAS G12C inhibitors, leading to the development of initial and acquired resistance to KRAS G12C inhibition. Based on this hypothesis, a phase 1-2 clinical trial, known as the KRYSTAL-1 study, was conducted in patients with metastatic colorectal cancer. The study demonstrated that the objective response rate was 19% with adagrasib monotherapy and 46% with the combination of adagrasib and cetuximab (an EGFR inhibitor), indicating that the addition of an EGFR inhibitor can overcome resistance. Building on this hypothesis, a phase 3 trial is currently underway for KRAS G12C inhibition plus EGFR blockade in metastatic colorectal cancer (ClinicalTrials.gov identifiers: NCT04793958, NCT05198934).

In this study, the aim is to investigate the efficacy of sotorasib (KRAS G12C inhibitor) plus panitumumab (EGFR inhibitor) in patients with advanced solid tumors harboring KRAS G12C mutations, who have failed standard treatments.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients who have consented to participate in the KOSMOS-II observational master study.
  • Age of 19 years or older.
  • Histologically confirmed locally advanced or metastatic solid tumors (excluding non-small cell lung cancer and colorectal cancer) with KRAS G12C mutation detected through local next-generation sequencing analysis.
  • Local advanced or metastatic disease with disease progression or unavailability of standard treatment options for the first-line anti-cancer therapy.
  • Measurable lesions according to RECIST v1.1 (lesions that have not experienced disease progression after radiation therapy are excluded).
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

  • Adequate bone marrow and organ function as described below:

    ① Bone Marrow: - Absolute neutrophil count (ANC) ≥ 1,500/mm3 - Platelet count (PLT) ≥ 100,000/mm3 - Hemoglobin (Hb) ≥ 9 g/dL

    ② Liver Function:

  • Total bilirubin ≤ 1.5 X upper limit of normal (ULN). If liver metastasis is present, total bilirubin up to ≤ 3 X ULN is allowed. For patients with Gilbert's syndrome, total bilirubin up to ≤ 3 X ULN and direct bilirubin within the normal range is allowed.

  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 X ULN (or ≤ 5 X ULN if liver metastasis is present).

    ③ Renal Function: - Creatinine clearance ≥ 30 mL/min/1.73m2 (using the Cockcroft-Gault formula).

  • Estimated life expectancy of at least 3 months according to the investigator's judgment.
  • Ability to take oral medications.
  • Understanding and compliance with the clinical trial protocol and ability to provide informed consent by signing the informed consent form.

Exclusion Criteria:

  • Patients who have not received previous sotorasib treatment or monoclonal antibodies against epidermal growth factor receptor (EGFR) such as cetuximab or panitumumab.
  • Absence of active brain metastasis or leptomeningeal metastasis (Patients with previously treated brain metastasis or leptomeningeal metastasis with radiation therapy and/or surgery [including radiosurgery] and are neurologically stable can be eligible for enrollment).
  • No significant cardiovascular events within the past 6 months, such as:

.NYHA Class 3 or higher congestive heart failure. .Unstable angina or myocardial infarction. .Uncontrolled or symptomatic atrial fibrillation. .QTc prolongation (> 480 milliseconds).

  • No history of stroke within the past 6 months (including transient ischemic attack).
  • No diagnosis of another malignancy within 2 years prior to enrollment (excluding superficial basal cell carcinoma or squamous cell carcinoma, cervical intraepithelial neoplasia, prostate cancer under active surveillance, and well-differentiated thyroid cancer that has undergone definitive surgery).
  • Pregnant or breastfeeding women.
  • Participants who do not agree to effective contraception* during the clinical trial.
  • Sexually active female participants of childbearing potential and their partners must agree to use medically acceptable contraception (e.g., male condoms, female condoms, or the combined use of barrier methods and spermicidal gel) during the clinical trial period and for up to 6 months after the last administration of the investigational drug.
  • Male participants who have not undergone vasectomy must agree to use barrier contraception (condoms) and are prohibited from providing sperm donations until 6 months after the last administration of the investigational drug.
  • Participants with active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, except under the following conditions:
  • Participants who are positive for HBsAg (Hepatitis B surface antigen) can be enrolled if ALT is within the normal range and HBV DNA is <2,000 IU/ml while receiving antiviral prophylaxis for hepatitis B reactivation.
  • Participants who are negative for HBsAg but positive for Hepatitis B core antibody (IgG anti-HBc) can be enrolled if HBV DNA is quantifiable but below the limit of quantification.
  • Participants who are positive for anti-HCV Ab can be enrolled if HCV RNA is quantifiable but below the limit of quantification.
  • Participants with planned major surgery during the clinical trial.
  • Other clinically significant disorders deemed unsuitable for the clinical trial by the investigator.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Oral sotorasib + IV Panitumumab
Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (> 1,000 mg).
Drug: Oral sotorasib + IV Panitumumab
Oral sotorasib at a dose of 960 mg once daily with Panitumumab is administered intravenously (IV) at a dose of 6 mg/kg every 14 days, infused over 60 minutes (≤ 1,000 mg) or 90 minutes (> 1,000 mg).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective response rate based on RECIST v1.1
Time Frame: Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).
Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).
Imaging tumor assessment time point after Cycle 1 Day 1 (each cycle is 14 days).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Korea University Anam Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 3, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 4, 2023

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 15, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 15, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 14, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KRAUS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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