Advanced Malignant Solid NeoplasmPhase 2NCT05638295
Testing the Use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Advanced Malignant Solid Neoplasm and Metastatic Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 180 sites in United States.
Trial summary
This phase II ComboMATCH treatment trial tests how well AMG 510 (sotorasib) with or without panitumumab works in treating patients with KRAS G12C mutant solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 180 sitesUnited States
- Study dates
- 1 Aug 2024to 31 Dec 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 33Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
180 sites in 1 country.
180 sites in 1 country
United States180 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Community Hospital of Anaconda
Anaconda, Montana, 59711
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106
ThedaCare Regional Cancer Center
Appleton, Wisconsin, 54911
Duluth Clinic Ashland
Ashland, Wisconsin, 54806
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Advocate Good Shepherd Hospital
Barrington, Illinois, 60010
ThedaCare Cancer Care - Berlin
Berlin, Wisconsin, 54923
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
Billings Clinic Cancer Center
Billings, Montana, 59101
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114
Trinity Health Medical Center - Brighton
Brighton, Michigan, 48114
Bristol Regional Medical Center
Bristol, Tennessee, 37620
Ballad Health Cancer Care - Bristol
Bristol, Virginia, 24201
Roswell Park Cancer Institute
Buffalo, New York, 14263
Aurora Cancer Care-Southern Lakes VLCC
Burlington, Wisconsin, 53105
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188
Trinity Health Medical Center - Canton
Canton, Michigan, 48188
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703
Vandalia Health/CAMC Institute for Academic Medicine
Charleston, West Virginia, 25304
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Chelsea Hospital
Chelsea, Michigan, 48118
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
Advocate Illinois Masonic Medical Center
Chicago, Illinois, 60657
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio, 43214
Riverside Methodist Hospital
Columbus, Ohio, 43214
Grant Medical Center
Columbus, Ohio, 43215
Doctors Hospital
Columbus, Ohio, 43228
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, 33065
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
AMG Crystal Lake - Oncology
Crystal Lake, Illinois, 60014
Aurora Saint Luke's South Shore
Cudahy, Wisconsin, 53110
Carle at The Riverfront
Danville, Illinois, 61832
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, 43015
Grady Memorial Hospital
Delaware, Ohio, 43015
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314
Advocate Good Samaritan Hospital
Downers Grove, Illinois, 60515
Columbus Oncology and Hematology Associates
Dublin, Ohio, 43016
Dublin Methodist Hospital
Dublin, Ohio, 43016
Essentia Health Cancer Center
Duluth, Minnesota, 55805
Prisma Health Cancer Institute - Easley
Easley, South Carolina, 29640
Carle Physician Group-Effingham
Effingham, Illinois, 62401
Crossroads Cancer Center
Effingham, Illinois, 62401
Advocate Sherman Hospital
Elgin, Illinois, 60123
Corewell Health Farmington Hills Hospital
Farmington Hills, Michigan, 48336
Cancer Hematology Centers - Flint
Flint, Michigan, 48503
Genesee Hematology Oncology PC
Flint, Michigan, 48503
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619
Aurora Health Care Germantown Health Center
Germantown, Wisconsin, 53022
Aurora Cancer Care-Grafton
Grafton, Wisconsin, 53024
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405
Aurora BayCare Medical Center
Green Bay, Wisconsin, 54311
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650
Advocate South Suburban Hospital
Hazel Crest, Illinois, 60429
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, 33021
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Mercyhealth Hospital and Cancer Center - Janesville
Janesville, Wisconsin, 53548
Regional Cancer Center at Johnson City Medical Center
Johnson City, Tennessee, 37604
Logan Health Medical Center
Kalispell, Montana, 59901
Aurora Cancer Care-Kenosha South
Kenosha, Wisconsin, 53142
Kettering Medical Center
Kettering, Ohio, 45429
Ballad Health Cancer Care - Kingsport
Kingsport, Tennessee, 37660
Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee, 37660
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912
OptumCare Cancer Care at Charleston
Las Vegas, Nevada, 89102
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89183
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
AMG Libertyville - Oncology
Libertyville, Illinois, 60048
Condell Memorial Hospital
Libertyville, Illinois, 60048
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154
The Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, 90025
Cedars-Sinai Medical Center
Los Angeles, California, 90048
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
OhioHealth Mansfield Hospital
Mansfield, Ohio, 44903
Aurora Bay Area Medical Group-Marinette
Marinette, Wisconsin, 54143
OhioHealth Marion General Hospital
Marion, Ohio, 43302
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938
Loyola University Medical Center
Maywood, Illinois, 60153
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176
Aurora Cancer Care-Milwaukee
Milwaukee, Wisconsin, 53209
Aurora Saint Luke's Medical Center
Milwaukee, Wisconsin, 53215
Aurora Sinai Medical Center
Milwaukee, Wisconsin, 53233
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Community Medical Center
Missoula, Montana, 59804
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, 36688
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
ThedaCare Regional Medical Center - Neenah
Neenah, Wisconsin, 54956
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
ThedaCare Cancer Care - New London
New London, Wisconsin, 54961
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Carle BroMenn Medical Center
Normal, Illinois, 61761
Carle Cancer Institute Normal
Normal, Illinois, 61761
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269
Advocate Christ Medical Center
Oak Lawn, Illinois, 60453-2699
Advocate Outpatient Center - Oak Lawn
Oak Lawn, Illinois, 60453
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914
ThedaCare Cancer Care - Oshkosh
Oshkosh, Wisconsin, 54904
Vince Lombardi Cancer Clinic - Oshkosh
Oshkosh, Wisconsin, 54904
VA Palo Alto Health Care System
Palo Alto, California, 94304
Advocate High Tech Medical Park
Palos Heights, Illinois, 60463
Advocate Lutheran General Hospital
Park Ridge, Illinois, 60068
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Saint Vincent Medical Center
Portland, Oregon, 97225
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854
Aurora Cancer Care-Racine
Racine, Wisconsin, 53406
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
VCU Massey Cancer Center at Stony Point
Richmond, Virginia, 23235
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Corewell Health Children's
Royal Oak, Michigan, 48073
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073
MyMichigan Medical Center Saginaw
Saginaw, Michigan, 48601
Oncology Hematology Associates of Saginaw Valley PC
Saginaw, Michigan, 48604
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864
Essentia Health Sandstone
Sandstone, Minnesota, 55072
Swedish Medical Center-First Hill
Seattle, Washington, 98122
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672
ThedaCare Cancer Care - Shawano
Shawano, Wisconsin, 54166
Vince Lombardi Cancer Clinic-Sheboygan
Sheboygan, Wisconsin, 53081
Memorial Hospital East
Shiloh, Illinois, 62269
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Springfield Clinic
Springfield, Illinois, 62702
Springfield Memorial Hospital
Springfield, Illinois, 62781
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
Aurora Medical Center in Summit
Summit, Wisconsin, 53066
MyMichigan Medical Center Tawas
Tawas City, Michigan, 48764
Scott and White Memorial Hospital
Temple, Texas, 76508
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085
Vince Lombardi Cancer Clinic-Two Rivers
Two Rivers, Wisconsin, 54241
Carle Cancer Center
Urbana, Illinois, 61801
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263
ThedaCare Cancer Care - Waupaca
Waupaca, Wisconsin, 54981
Aurora Cancer Care-Milwaukee West
Wauwatosa, Wisconsin, 53226
Aurora West Allis Medical Center
West Allis, Wisconsin, 53227
Saint Mary's Oncology/Hematology Associates of West Branch
West Branch, Michigan, 48661
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090
Huron Gastroenterology PC
Ypsilanti, Michigan, 48106
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197
About this study
Official title: A Randomized Phase II Study of AMG 510 (Sotorasib) With or Without Panitumumab in Advanced Solid Tumors: A ComboMATCH Treatment Trial
This phase II ComboMATCH treatment trial tests how well AMG 510 (sotorasib) with or without panitumumab works in treating patients with KRAS G12C mutant solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Sotorasib is in a class of medications called KRAS inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells. Panitumumab is in a class of medications called monoclonal antibodies. It works by slowing or stopping the growth of cancer cells. Giving combination panitumumab and sotorasib may kill more tumor cells in patients with advanced solid tumors with KRAS G12C mutation.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab as compared to AMG 510 (sotorasib) alone in patients with advanced/metastatic KRAS G12C mutated solid tumors (except colorectal carcinoma [CRC] and non-small cell lung carcinoma [NSCLC]) as measured by progression free survival (Cohort 1).
II. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab in patients with advanced/metastatic KRAS G12C mutated solid tumors that have progressed on a prior KRAS G12C inhibitor as measured by response rate (Cohort 2).
SECONDARY OBJECTIVES:
- To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab as compared to AMG 510 alone in patients with advanced/metastatic KRAS G12C mutated solid tumors (except CRC and NSCLC) as measured by response rate, disease control rate, and overall survival (Cohort 1).
II, To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab in patients with advanced/metastatic KRAS G12C mutated solid tumors that have progressed on a prior KRAS G12C inhibitor as measured by disease control rate, progression free survival (PFS), and overall survival (Cohort 2).
III. To further evaluate the safety and tolerability of the combination of AMG 510 (sotorasib) and panitumumab.
IV. To collect tissue and provide it to the ComboMATCH Registration Protocol to assess concordance between the diagnostic tumor mutation profile generated by the Designated Laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol.
CORRELATIVE EXPLORATORY OBJECTIVES:
- To investigate the impact of concomitant mutations on the clinical benefit. II. To evaluate if changes in circulating tumor DNA (ctDNA) over time correlate with response to treatment.
III. To evaluate the relative mutant allele fraction of KRAS mutation as a predictor of clinical benefit.
IV. To evaluate if ERK 1/2 and PI3K pathway activation correlate with response and/or resistance.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
COHORT I: Patients who have never received a KRAS G12C inhibitor are randomized to arms A or B.
ARM A: Patients receive sotorasib orally (PO) once daily (QD) on days 1-28 and panitumumab intravenously (IV) on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and computed tomography (CT) or magnetic resonance imaging (MRI) on study.
ARM B: Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.
COHORT II: Patients who have received a KRAS G12C inhibitor are assigned to arm C.
ARM C: Patients receive combination therapy as in Arm A.
After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 36 months.
- Being tested
- Biopsy Procedure, Biospecimen Collection, Computed Tomography, Magnetic Resonance Imaging, Panitumumab
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
PanitumumabBiological
Also called ABX-EGF, ABX-EGF Monoclonal Antibody, ABX-EGF, Clone E7.6.3, E7.6.3
Given IV
SotorasibDrug
Also called AMG 510, AMG-510, AMG510, Lumakras
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Cohort I Arm A (sotorasib, panitumumab) | Experimental | Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Panitumumab; Drug: Sotorasib |
| Cohort I Arm B (sotorasib) | Active comparator | Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Sotorasib |
| Cohort II (sotorasib, panitumumab) | Experimental | Patients receive combination therapy as in Arm A. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Panitumumab; Drug: Sotorasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS) (Cohort I)
PFS will be compared between the arms using a one-sided log rank test with 10% type I error. Cox's proportional hazards model will be used to estimate the PFS hazard ratio between the treatment arms and a two-sided 80% confidence interval will be reported (to correspond to the one-sided 10% type I error). Confidence intervals on most other quantities will use the two-sided 90% level.
Measured: From registration to documented disease progression or death from any cause, assessed up to 3 years
Best objective response (Cohort II)
Will be evaluated using the criteria defined by Response Evaluation Criteria in Solid Tumors) version 1.1 for patients with solid tumors.
Measured: From the start of the treatment until disease progression/recurrence, assessed up to 3 years
Overall response rate (ORR) (Cohort II)
The exact 90% confidence interval on the ORR (determined using the method of Atkinson and Brown) will be reported. If the number of analyzable cases is less than 35, a 5% one-sided test will still be used.
Measured: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 3 years
Secondary outcomes (5)
Overall survival (OS) (Cohort I)
OS distributions by treatment will be estimated and 90% confidence intervals on estimated rates at 6 and 12 months will be reported. The OS hazard ratio will be estimated using Cox proportional hazards model and a 90% confidence interval reported.
Measured: Up to 3 years
ORR (Cohort I)
Will be compared using Fisher's exact test and exact 90% confidence intervals for the rates in each arm will be computed.
Measured: Up to 3 years
Disease control rates (Cohort I)
Will be compared using Fisher's exact test and exact 90% confidence intervals for the rates in each arm will be computed.
Measured: From the start of the treatment until the criteria for progression are met, assessed up to 3 years
PFS (Cohort II)
Will be estimated and 90% confidence intervals on estimated rates will be reported.
Measured: At 6 and 12 months, assessed up to 3 years
OS (Cohort II)
Will be estimated and 90% confidence intervals on estimated rates will be reported.
Measured: At 6 and 12 months, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start1 Aug 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kristen R Spencer, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05638295
- Sponsor's protocol ID
- NCI-2022-09876
- Other IDs
- NCI-2022-09876, EAY191-E5, EAY191-E5, U10CA180820
- Status last verified
- Oct 2026
- First submitted
- 2 Dec 2022
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.