Various Cancer Types

EAY191-E5



Testing the use of AMG 510 (Sotorasib) and Panitumumab as a Targeted Treatment for KRAS G12C Mutant Solid Tumor Cancers (A ComboMATCH Treatment Trial)

STATUS: Active


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.
  • 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 sexual orientation or 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

United States
AL
Birmingham
University of Alabama at Birmingham Cancer Center
Contact: Site Public Contact
Email: tmyrick@uab.edu

IA
Ankeny
Mission Cancer and Blood - Ankeny
Contact: Site Public Contact

Des Moines
Mission Cancer and Blood - Des Moines
Contact: Site Public Contact

ID
Boise
Saint Alphonsus Cancer Care Center-Boise
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Caldwell
Saint Alphonsus Cancer Care Center-Caldwell
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Coeur D'Alene
Kootenai Health - Coeur d'Alene
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Nampa
Saint Alphonsus Cancer Care Center-Nampa
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Post Falls
Kootenai Clinic Cancer Services - Post Falls
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Sandpoint
Kootenai Clinic Cancer Services - Sandpoint
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

IL
Chicago
John H Stroger Jr Hospital of Cook County
Contact: Site Public Contact

Danville
Carle at The Riverfront
Contact: Site Public Contact
Email: Research@Carle.com

Decatur
Cancer Care Specialists of Illinois - Decatur
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Decatur Memorial Hospital
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Effingham
Carle Physician Group-Effingham
Contact: Site Public Contact
Email: Research@carle.com

Crossroads Cancer Center
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Mattoon
Carle Physician Group-Mattoon/Charleston
Contact: Site Public Contact
Email: Research@carle.com

Shiloh
Memorial Hospital East
Contact: Site Public Contact
Email: dschwab@wustl.edu

Springfield
Memorial Medical Center
Contact: Site Public Contact
Email: pallante.beth@mhsil.com

Southern Illinois University School of Medicine
Contact: Site Public Contact

Springfield Clinic
Contact: Site Public Contact

Urbana
Carle Cancer Center
Contact: Site Public Contact
Email: Research@carle.com

ME
Brewer
Lafayette Family Cancer Center-EMMC
Contact: Site Public Contact

MI
Ann Arbor
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Brighton
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health Medical Center - Brighton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Canton
Trinity Health IHA Medical Group Hematology Oncology - Canton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health Medical Center - Canton
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Chelsea
Chelsea Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Dearborn
Beaumont Hospital - Dearborn
Contact: Site Public Contact

Farmington Hills
Beaumont Hospital - Farmington Hills
Contact: Site Public Contact

Flint
Genesee Cancer and Blood Disease Treatment Center
Contact: Site Public Contact
Email: wstrong@ghci.org

Genesee Hematology Oncology PC
Contact: Site Public Contact
Email: wstrong@ghci.org

Genesys Hurley Cancer Institute
Contact: Site Public Contact
Email: wstrong@ghci.org

Hurley Medical Center
Contact: Site Public Contact
Email: wstrong@ghci.org

Lansing
University of Michigan Health - Sparrow Lansing
Contact: Site Public Contact
Email: harsha.trivedi@umhsparrow.org

Livonia
Trinity Health Saint Mary Mercy Livonia Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Royal Oak
Beaumont Children's Hospital-Royal Oak
Contact: Site Public Contact

William Beaumont Hospital-Royal Oak
Contact: Site Public Contact

Troy
William Beaumont Hospital - Troy
Contact: Site Public Contact

Ypsilanti
Huron Gastroenterology PC
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

MN
Deer River
Essentia Health - Deer River Clinic
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Duluth
Essentia Health Cancer Center
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Hibbing
Essentia Health Hibbing Clinic
Contact: Site Public Contact

Sandstone
Essentia Health Sandstone
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Virginia
Essentia Health Virginia Clinic
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

MO
Cape Girardeau
Saint Francis Medical Center
Contact: Site Public Contact
Email: sfmc@sfmc.net

Creve Coeur
Siteman Cancer Center at West County Hospital
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Saint Louis
Siteman Cancer Center at Christian Hospital
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Siteman Cancer Center-South County
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Washington University School of Medicine
Contact: Site Public Contact
Email: info@siteman.wustl.edu

Saint Peters
Siteman Cancer Center at Saint Peters Hospital
Contact: Site Public Contact
Email: info@siteman.wustl.edu

MT
Anaconda
Community Hospital of Anaconda
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Billings
Billings Clinic Cancer Center
Contact: Site Public Contact
Email: research@billingsclinic.org

Bozeman
Bozeman Health Deaconess Hospital
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Great Falls
Benefis Sletten Cancer Institute
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Missoula
Community Medical Center
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

NM
Albuquerque
University of New Mexico Cancer Center
Contact: Site Public Contact
Email: HSC-ClinicalTrialInfo@salud.unm.edu

NV
Henderson
OptumCare Cancer Care at Seven Hills
Contact: Site Public Contact
Email: research@sncrf.org

Las Vegas
OptumCare Cancer Care at Charleston
Contact: Site Public Contact
Email: research@sncrf.org

OptumCare Cancer Care at Fort Apache
Contact: Site Public Contact
Email: research@sncrf.org

OH
Columbus
Columbus Oncology and Hematology Associates Inc
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Doctors Hospital
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Grant Medical Center
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Riverside Methodist Hospital
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Dayton
Dayton Physician LLC - Englewood
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Delaware
Delaware Health Center-Grady Cancer Center
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Grady Memorial Hospital
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Dublin
Columbus Oncology and Hematology Associates
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Dublin Methodist Hospital
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Kettering
Kettering Medical Center
Contact: Site Public Contact
Email: clinical.trials@daytonncorp.org

Mansfield
OhioHealth Mansfield Hospital
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

Marion
OhioHealth Marion General Hospital
Contact: Site Public Contact
Email: Jennifer.Sexton@ohiohealth.com

OK
Oklahoma City
University of Oklahoma Health Sciences Center
Contact: Site Public Contact
Email: ou-clinical-trials@ouhsc.edu

OR
Ontario
Saint Alphonsus Cancer Care Center-Ontario
Contact: Site Public Contact
Email: mccinfo@mtcancer.org

Portland
Providence Portland Medical Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

Providence Saint Vincent Medical Center
Contact: Site Public Contact
Email: CanRsrchStudies@providence.org

PA
Philadelphia
ECOG-ACRIN Cancer Research Group
Contact: Kristen Renee Spencer
Email: Kristen.Spencer@nyulangone.org

WI
Ashland
Duluth Clinic Ashland
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

La Crosse
Gundersen Lutheran Medical Center
Contact: Site Public Contact
Email: cancerctr@gundersenhealth.org

Madison
University of Wisconsin Carbone Cancer Center - University Hospital
Contact: Site Public Contact
Email: clinicaltrials@cancer.wisc.edu

PRIMARY OBJECTIVES:
I. 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:
I. 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:
I. 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.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its National Clinical Trials Network. This trial is part of the ComboMATCH precision medicine intiative.


EAY191-E5 / ComboMATCH-E5 Home Page
ECOG-ACRIN Cancer Research Group