New drug combo aims to outsmart Hard-to-Treat cancers

NCT ID NCT05638295

Disease control Sponsor: National Cancer Institute (NCI) Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This phase II trial tests whether adding panitumumab to sotorasib works better than sotorasib alone for advanced solid tumors that have a KRAS G12C mutation. About 105 adults with these cancers will be randomly assigned to one of two groups. The main goal is to see if the combination delays cancer growth longer.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: sotorasib (AMG 510) and panitumumab
What this could lead to: If successful, this could point toward a more effective combination treatment for advanced solid tumors with a KRAS G12C mutation.
What could go wrong: This is a mid-stage trial with only 105 participants, so results may not apply to all patients. Combining drugs can also increase side effects.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 105 people

The number the study aims to enrol. It can still change while the study runs.

Started

Aug 2024

Expected to finish

Dec 2028

An estimate. End dates often move.

Lead sponsor

A government research agency

The lead sponsor is the US National Institutes of Health.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-E5 based on the presence of an actionable mutation as defined in EAY191 * Patient must be enrolled on the ComboMATCH Registration Protocol (EAY191) at the time of registration/randomization to the EAY191-E5 study * Patient must be \>= 18 years of age * Patient must have a KRAS G12C alteration as determined by the ComboMATCH screening assessment * Patient must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191-E5) * NOTE: The current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website: www.ctsu.org (final URL pending) * NOTE: Novel/Dynamic aMOI can be submitted for review per the process described in the ComboMATCH registration protocol * Patient must have cytologically/histologically confirmed advanced/metastatic solid tumor * Patient must have progressed on at least one line of standard of care therapy in the advanced/metastatic setting * NOTE: Patients who have progressed on a prior human epidermal growth factor receptor (EGFR) inhibitor will meet this criterion * Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 (or Karnofsky performance status \>= 60%) * Patient must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) documented by imaging obtained within 28 days prior to registration/randomization * Patient must not have any serious active infection within 4 weeks prior to EAY191-E5 registration/randomization (e.g., requiring hospitalization and/or intravenous \[IV\] antibiotics) or currently receiving oral or IV antibiotics for the treatment of infection. Patients receiving prophylactic antibiotics are eligible * Patient must have the ability to retain oral medication and not have any clinically significant gastrointestinal abnormalities that might alter absorption * Patient must not have any history of or current evidence of non-infectious interstitial lung disease (ILD)/pneumonitis * Patient must not have a history of allergic reactions attributed to either of the study agents or to agents of similar chemical or biologic composition * Patient must have completed full treatment cycle 21 days prior to EAY191-E5 registration/randomization if they have received prior chemotherapy, biological cancer therapy, radiation therapy or an investigational agent/device. Patients must have recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse events due to prior cancer therapy (with the exception of alopecia) * Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to registration/randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) * Patient must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for at least 6 months after the last dose of protocol treatment. Patients must not breastfeed while receiving protocol treatment and for one week (7 days) after the last dose of AMG 510 (sotorasib) and 2 months after the last dose of panitumumab * Patients must not have neuropathy ≥ grade 2 within 14 days prior to registration/randomization * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression * Human immunodeficiency virus (HIV)-infected patients no effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Patients with known history or current symptoms of cardiac history, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trail, patients should be class 2B or better * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 28 days prior to protocol registration/randomization) * Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (\[SGPT\]) \< 3 x institutional upper limit of normal (obtained ≤ 28 days prior to protocol registration/randomization) * Creatinine =\< 1.5 x institutional ULN OR creatinine clearance \> 50 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 mg/dL as per Cockcroft-Gault (obtained ≤ 28 days prior to protocol registration/randomization) * COHORT I: Patient must not have colorectal cancer or non-small cell lung cancer * COHORT I: Patient must not have been previously treated with a KRAS G12C inhibitor * COHORT II: Patient must have progressed after treatment at the recommended phase II dose (RP2D) of any KRAS G12C inhibitor * NOTE: Patients on cohort 1 who experience progression on Regimen 2 (AMG 510 \[sotorasib\] alone) may be eligible to enroll on cohort 2 and receive combination treatment with panitumumab and AMG 510 (sotorasib). Patients must meet performance status requirements and laboratory values as above and must be begin treatment within 7 days of enrollment. Migration to cohort 2 must take place within 6 months of progression, with no intervening anti-cancer therapy given. * NOTE: Cohort migration following disease progression is dependent on a slot being available. MATCHBox makes the new treatment assignment following initiation of a step 2 registration for this treatment trial * COHORT II: Patient must not have been previously treated with a KRAS G12C inhibitor in combination with an EGFR inhibitor

Get updates

Get notified about this study

Vår säkerhetsrekommendation!

Genom att skicka in godkänner du våra Användarvillkor

Conditions

The condition(s) this trial relates to.

cancer metastatic malignant neoplasm Neoplasm Metastasis

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Advanced malignant solid neoplasm Metastatic malignant solid neoplasm

Contacts and locations

Locations

AMG Crystal Lake - Oncology

Crystal Lake, Illinois, 60014, United States
AMG Libertyville - Oncology

Libertyville, Illinois, 60048, United States
Advocate Christ Medical Center

Oak Lawn, Illinois, 60453-2699, United States
Advocate Good Samaritan Hospital

Downers Grove, Illinois, 60515, United States
Advocate Good Shepherd Hospital

Barrington, Illinois, 60010, United States
Advocate High Tech Medical Park

Palos Heights, Illinois, 60463, United States
Advocate Illinois Masonic Medical Center

Chicago, Illinois, 60657, United States
Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States
Advocate Outpatient Center - Oak Lawn

Oak Lawn, Illinois, 60453, United States
Advocate Sherman Hospital

Elgin, Illinois, 60123, United States
Advocate South Suburban Hospital

Hazel Crest, Illinois, 60429, United States
Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States
Asplundh Cancer Pavilion

Willow Grove, Pennsylvania, 19090, United States
Aurora Bay Area Medical Group-Marinette

Marinette, Wisconsin, 54143, United States
Aurora BayCare Medical Center

Green Bay, Wisconsin, 54311, United States
Aurora Cancer Care-Grafton

Grafton, Wisconsin, 53024, United States
Aurora Cancer Care-Kenosha South

Kenosha, Wisconsin, 53142, United States
Aurora Cancer Care-Milwaukee

Milwaukee, Wisconsin, 53209, United States
Aurora Cancer Care-Milwaukee West

Wauwatosa, Wisconsin, 53226, United States
Aurora Cancer Care-Racine

Racine, Wisconsin, 53406, United States
Aurora Cancer Care-Southern Lakes VLCC

Burlington, Wisconsin, 53105, United States
Aurora Health Care Germantown Health Center

Germantown, Wisconsin, 53022, United States
Aurora Medical Center in Summit

Summit, Wisconsin, 53066, United States
Aurora Saint Luke's Medical Center

Milwaukee, Wisconsin, 53215, United States
Aurora Saint Luke's South Shore

Cudahy, Wisconsin, 53110, United States
Aurora Sinai Medical Center

Milwaukee, Wisconsin, 53233, United States
Aurora West Allis Medical Center

West Allis, Wisconsin, 53227, United States
Ballad Health Cancer Care - Bristol

Bristol, Virginia, 24201, United States
Ballad Health Cancer Care - Kingsport

Kingsport, Tennessee, 37660, United States
Benefis Sletten Cancer Institute

Great Falls, Montana, 59405, United States
Billings Clinic Cancer Center

Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715, United States
Bristol Regional Medical Center

Bristol, Tennessee, 37620, United States
Cancer Care Center of O'Fallon

O'Fallon, Illinois, 62269, United States
Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, 62526, United States
Cancer Hematology Centers - Flint

Flint, Michigan, 48503, United States
Carle BroMenn Medical Center

Normal, Illinois, 61761, United States
Carle Cancer Center

Urbana, Illinois, 61801, United States
Carle Cancer Institute Normal

Normal, Illinois, 61761, United States
Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States
Carle at The Riverfront

Danville, Illinois, 61832, United States
Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States
Chelsea Hospital

Chelsea, Michigan, 48118, United States
Columbus Oncology and Hematology Associates

Dublin, Ohio, 43016, United States
Columbus Oncology and Hematology Associates Inc

Columbus, Ohio, 43214, United States
Community Hospital of Anaconda

Anaconda, Montana, 59711, United States
Community Medical Center

Missoula, Montana, 59804, United States
Condell Memorial Hospital

Libertyville, Illinois, 60048, United States
Corewell Health Beaumont Troy Hospital

Troy, Michigan, 48085, United States
Corewell Health Children's

Royal Oak, Michigan, 48073, United States
Corewell Health Dearborn Hospital

Dearborn, Michigan, 48124, United States
Corewell Health Farmington Hills Hospital

Farmington Hills, Michigan, 48336, United States
Corewell Health William Beaumont University Hospital

Royal Oak, Michigan, 48073, United States
Crossroads Cancer Center

Effingham, Illinois, 62401, United States
Dayton Physician LLC - Englewood

Dayton, Ohio, 45415, United States
Decatur Memorial Hospital

Decatur, Illinois, 62526, United States
Delaware Health Center-Grady Cancer Center

Delaware, Ohio, 43015, United States
Doctors Hospital

Columbus, Ohio, 43228, United States
Dublin Methodist Hospital

Dublin, Ohio, 43016, United States
Duluth Clinic Ashland

Ashland, Wisconsin, 54806, United States
Essentia Health - Deer River Clinic

Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center

Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic

Hibbing, Minnesota, 55746, United States
Essentia Health Sandstone

Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic

Virginia, Minnesota, 55792, United States
Genesee Hematology Oncology PC

Flint, Michigan, 48503, United States
Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States
Grady Memorial Hospital

Delaware, Ohio, 43015, United States
Grant Medical Center

Columbus, Ohio, 43215, United States
Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States
Hurley Medical Center

Flint, Michigan, 48503, United States
Huron Gastroenterology PC

Ypsilanti, Michigan, 48106, United States
John H Stroger Jr Hospital of Cook County

Chicago, Illinois, 60612, United States
Kettering Medical Center

Kettering, Ohio, 45429, United States
Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, 83864, United States
Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, 83814, United States
Lafayette Family Cancer Center-EMMC

Brewer, Maine, 04412, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States
Logan Health Medical Center

Kalispell, Montana, 59901, United States
Loyola University Medical Center

Maywood, Illinois, 60153, United States
Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States
Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States
Memorial Hospital East

Shiloh, Illinois, 62269, United States
Mercyhealth Hospital and Cancer Center - Janesville

Janesville, Wisconsin, 53548, United States
MyMichigan Medical Center Saginaw

Saginaw, Michigan, 48601, United States
MyMichigan Medical Center Tawas

Tawas City, Michigan, 48764, United States
NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States
National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States
OhioHealth Mansfield Hospital

Mansfield, Ohio, 44903, United States
OhioHealth Marion General Hospital

Marion, Ohio, 43302, United States
Oncology Hematology Associates of Saginaw Valley PC

Saginaw, Michigan, 48604, United States
OptumCare Cancer Care at Charleston

Las Vegas, Nevada, 89102, United States
OptumCare Cancer Care at Fort Apache

Las Vegas, Nevada, 89183, United States
Prisma Health Cancer Institute - Butternut

Greenville, South Carolina, 29605, United States
Prisma Health Cancer Institute - Easley

Easley, South Carolina, 29640, United States
Prisma Health Cancer Institute - Eastside

Greenville, South Carolina, 29615, United States
Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605, United States
Prisma Health Cancer Institute - Greer

Greer, South Carolina, 29650, United States
Prisma Health Cancer Institute - Seneca

Seneca, South Carolina, 29672, United States
Prisma Health Cancer Institute - Spartanburg

Boiling Springs, South Carolina, 29316, United States
Providence Portland Medical Center

Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States
Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States
Regional Cancer Center at Johnson City Medical Center

Johnson City, Tennessee, 37604, United States
Riverside Methodist Hospital

Columbus, Ohio, 43214, United States
Roswell Park Cancer Institute

Buffalo, New York, 14263, United States
Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States
Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States
Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho, 83605, United States
Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, 83687, United States
Saint Alphonsus Cancer Care Center-Ontario

Ontario, Oregon, 97914, United States
Saint Francis Medical Center

Cape Girardeau, Missouri, 63703, United States
Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States
Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, 83619, United States
Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, 83642, United States
Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, 83687, United States
Saint Mary's Oncology/Hematology Associates of West Branch

West Branch, Michigan, 48661, United States
Scott and White Memorial Hospital

Temple, Texas, 76508, United States
Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States
Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States
Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States
Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States
Springfield Clinic

Springfield, Illinois, 62702, United States
Springfield Memorial Hospital

Springfield, Illinois, 62781, United States
Swedish Medical Center-First Hill

Seattle, Washington, 98122, United States
The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, 90025, United States
ThedaCare Cancer Care - Berlin

Berlin, Wisconsin, 54923, United States
ThedaCare Cancer Care - New London

New London, Wisconsin, 54961, United States
ThedaCare Cancer Care - Oshkosh

Oshkosh, Wisconsin, 54904, United States
ThedaCare Cancer Care - Shawano

Shawano, Wisconsin, 54166, United States
ThedaCare Cancer Care - Waupaca

Waupaca, Wisconsin, 54981, United States
ThedaCare Regional Cancer Center

Appleton, Wisconsin, 54911, United States
ThedaCare Regional Medical Center - Neenah

Neenah, Wisconsin, 54956, United States
Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, 48188, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, 48118, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197, United States
Trinity Health Medical Center - Brighton

Brighton, Michigan, 48114, United States
Trinity Health Medical Center - Canton

Canton, Michigan, 48188, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, 48106, United States
Trinity Health Saint Joseph Mercy Oakland Hospital

Pontiac, Michigan, 48341, United States
Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa, 50263, United States
UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Coral Springs

Coral Springs, Florida, 33065, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States
UM Sylvester Comprehensive Cancer Center at Hollywood

Hollywood, Florida, 33021, United States
UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States
University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States
University of Illinois

Chicago, Illinois, 60612, United States
University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States
University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States
University of Michigan Health - Sparrow Lansing

Lansing, Michigan, 48912, United States
University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States
University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States
University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36688, United States
University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States
VA Palo Alto Health Care System

Palo Alto, California, 94304, United States
VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States
VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States
Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States
Vince Lombardi Cancer Clinic - Oshkosh

Oshkosh, Wisconsin, 54904, United States
Vince Lombardi Cancer Clinic-Sheboygan

Sheboygan, Wisconsin, 53081, United States
Vince Lombardi Cancer Clinic-Two Rivers

Two Rivers, Wisconsin, 54241, United States
Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States
Washington University School of Medicine

St Louis, Missouri, 63110, United States
Wellmont Holston Valley Hospital and Medical Center

Kingsport, Tennessee, 37660, United States
West Virginia University Charleston Division

Charleston, West Virginia, 25304, United States

More trials for these conditions

Other studies related to the condition(s) this trial covers.