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Active, not recruitingNCT04625647Updated Dec 5, 2025

Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)

A Phase 2 interventional study of Sotorasib in Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, sponsored by SWOG Cancer Research Network. Active, not recruiting at 829 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-05.

Sponsored by SWOG Cancer Research Network · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
116
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back (recurrent) and has a specific mutation in the KRAS gene, known as KRAS G12C. Mutations in this gene may cause the cancer to grow. AMG 510, a targeted treatment against the KRAS G12C mutation, may help stop the growth of tumor cells.

Read the detailed description

PRIMARY OBJECTIVE:

I. To evaluate the response rate (confirmed, complete or partial) of AMG 510 in participants with KRAS\^G12C mutated stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. To evaluate investigator assessed progression-free survival (IA-PFS) within each cohort.

II. To evaluate overall survival (OS) within each cohort. III. To evaluate duration of response (DOR) among responders within each cohort.

IV. To evaluate the frequency and severity of toxicities within the full study population (all cohorts combined).

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To evaluate the association between clinical outcomes (response, IA-PFS, OS) and other co-mutations (e.g., CDKN2A/B/C, ATM, PIK3CA) identified by the Foundation Medicine Inc (FMI) FoundationOne CDx from LUNGMAP, within cohorts and across the full study population of KRAS\^G12C positive participants.

II. To evaluate the association between clinical outcomes (response, IA-PFS, OS) and PD-L1 total proportion score determined by screening in LUNGMAP, within cohorts and across the full study population of KRAS\^G12C positive participants.

III. To evaluate the association between clinical outcomes (response, IA-PFS, OS) and Tumor Mutational Burden Score determined by the FMI FoundationOne CDx from LUNGMAP, within cohorts and across the full study population of KRAS\^G12C positive participants.

IV. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at pre-treatment on cycle 1 day 1, cycle 2 day 1, cycle 3 day 1, and at progression for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) and association with clinical outcomes.

Note: The translational medicine proposal to use these specimens will be submitted as a revision to CTEP for approval, prior to the SWOG Statistical and Data Management Center (SDMC) review of assay results.

OUTLINE:

Patients receive AMG 510 orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years if the disease has not gotten worse at the time of finishing study treatment. If the disease has gotten worse, patients are followed up every 6 months for 2 years, then at the end of the 3 years from the time they go on study.

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Conditions studied

  • Lung Adenocarcinoma
  • Lung Non-Small Cell Carcinoma
  • Recurrent Lung Non-Squamous Non-Small Cell Carcinoma
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Participants must be assigned to S1900E. Assignment to S1900E is determined by the LUNGMAP protocol genomic profiling using the FoundationOne assay. Biomarker eligibility for S1900E is based on the identification of a KRAS\^G12C mutation
  • Participants must have confirmed stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC). Mixed histology NSCLC with less than 50% squamous component is allowed
  • Participants must have measurable disease documented by computed tomography (CT) or magnetic resonance imaging (MRI). The CT from a combined positron emission tomography (PET)/CT may be used to document only non-measurable disease unless it is of diagnostic quality. Measurable disease must be assessed within 28 days prior to sub-study registration. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Non-measurable disease must be assessed within 42 days prior to sub-study registration. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
  • Participants must have a CT or MRI scan of the brain to evaluate for central nervous system (CNS) disease within 42 days prior to sub-study registration
  • Participants with known human immunodeficiency virus (HIV) infection must be receiving anti-retroviral therapy and have an undetectable viral load at their most recent viral load test within 6 months prior to sub-study registration
  • Participants with EGFR sensitizing mutations, EGFR T790M mutation, ALK gene fusion, ROS1 gene rearrangement, or BRAF V600E mutation must have progressed following all standard of care targeted therapy
  • Participants with spinal cord compression or brain metastases must have received local treatment to these metastases and remained clinically controlled and asymptomatic for at least 7 days following stereotactic radiation and/or 14 days following whole brain radiation, and prior to sub-study registration
  • Participants must have received at least one line of systemic treatment for stage IV or recurrent NSCLC
  • Participants must have progressed (in the opinion of the treating physician) following the most recent line of systemic therapy for NSCLC
  • Participants must have recovered (=\< grade 1) from side effects of prior therapy. The exception is if a side effect from a prior treatment is known to be permanent without expected further recovery or resolution (i.e., endocrinopathy from immunotherapy or cisplatin neurotoxicity)
  • Participants must be able to swallow tablets whole
  • Pre-study history and physical exam must be obtained within 28 days prior to sub-study registration
  • Absolute neutrophil count (ANC) >= 1,500/uL obtained within 28 days prior to sub-study registration
  • Platelet count >= 75,000/uL obtained within 28 days prior to sub-study registration
  • Hemoglobin >= 9 g/dL obtained within 28 days prior to sub-study registration
  • Serum bilirubin =\< institutional upper limit of normal (IULN) within 28 days prior to sub-study registration
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2 x IULN within 28 days prior to sub-study registration. For participants with liver metastases, and ALT and AST must be =\< 5 x IULN
  • Participants must have a serum creatinine =\< 1.5 x IULN or calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to sub-study registration
  • Participants must have Zubrod performance status 0-1 documented within 28 days prior to sub-study registration
  • Participants of reproductive potential must have a negative serum pregnancy test within 28 days prior to sub-study registration
  • Participants must agree to have blood specimens submitted for circulating tumor DNA (ctDNA)
  • Participants must be offered the opportunity to participate in specimen banking and in correlative studies for collection and future use of specimens. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System
  • Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines

    • NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
  • Participants with impaired decision-making capacity are eligible as long as their neurological or psychological condition does not preclude their safe participation in the study (e.g., tracking pill consumption and reporting adverse events to the investigator). For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations

Exclusion criteria

Exclusion Criteria:

  • Participants with spinal cord compression or brain metastases must not have residual neurological dysfunction, unless no further recovery is expected, and the participant has been stable on weaning doses of corticosteroids prior to sub-study registration
  • Participants must not have leptomeningeal disease unless: (1) asymptomatic and (2) only detected on radiographic imaging (i.e., not present in cytology from cerebral spinal fluid [CSF] if CSF sampled)
  • Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration
  • Participants must not have received any radiation therapy within 14 days prior to sub-study registration, with the exception of stereotactic radiation to CNS metastases which must have been completed at least 7 days prior to sub-study registration
  • Participants must not have received prior AMG 510 or other KRAS\^G12C specific inhibitor
  • Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment while receiving treatment on this study
  • Participants must not have had a major surgery within 14 days prior to sub-study registration. Participant must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
  • Participants must not have any grade III/IV cardiac disease as defined by the New York Heart Association criteria (i.e., participants with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 6 months, or serious uncontrolled cardiac arrhythmia
  • Participants must not have a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Participants must not have gastrointestinal disorders that may impact drug absorption
  • Participants must not have received strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days prior to sub-study registration and must not be planning to use strong inducers of CYP3A4 throughout protocol treatment
  • Participants must not have received CYP3A4 sensitive substrates (with a narrow therapeutic window) within 14 days prior to sub-study registration and must not be planning to use CYP3A4 sensitive substrates (with a narrow therapeutic window) throughout protocol treatment
  • Participants must not be pregnant or nursing. Participants with uteri must have agreed to use an effective contraceptive method for at least one month after the last dose of AMG 510. Participants with sperm must have agreed to use an effective contraceptive method for at least 3 months after the last dose of AMG 510. Participants are considered to be of "reproductive potential" if they have had menses at any time in the preceding 12 consecutive months and no prior oophorectomy and/or hysterectomy. In addition to routine contraceptive methods, "effective contraception" for participants with uteri also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. Acceptable methods of birth control for participants with sperm include sexual abstinence (refraining from heterosexual intercourse); vasectomy with testing showing there is no sperm in the semen; bilateral tubal ligation or occlusion in the partner; or a condom (the female partner should also consider a form of birth control). However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
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Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
116 participants (estimated)

Study arms

  • Experimental
    Treatment (AMG 510)

    Patients receive AMG 510 PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Drug: Sotorasib

Interventions

  • DrugSotorasib

    Given PO

    Also known as: AMG 510, AMG-510, AMG510

05

What researchers measure

Primary outcomes

  1. Response rate (confirmed, complete or partial)

    Time frame: Up to 3 years

Secondary outcomes

  1. Incidence of adverse events

    The frequency and grade of individual toxicities attributable to treatment will be estimated.

    Time frame: Up to 3 years

  2. Progression free survival

    Will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the Brookmeyer-Crowley method and about landmark time points will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Binary proportions and associated confidence intervals will be estimated for within cohort objectives. With participants in Cohort 1 and 3 and participants in Cohort 2, binary proportions can be estimated to within 16% and 20% with 95% confidence, respectively.

    Time frame: Up to 3 years

  3. Overall survival

    Will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the Brookmeyer-Crowley method and about landmark time points will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Binary proportions and associated confidence intervals will be estimated for within cohort objectives. With participants in Cohort 1 and 3 and participants in Cohort 2, binary proportions can be estimated to within 16% and 20% with 95% confidence, respectively.

    Time frame: Up to 3 years

  4. Duration of response

    Will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the Brookmeyer-Crowley method and about landmark time points will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Binary proportions and associated confidence intervals will be estimated for within cohort objectives. With participants in Cohort 1 and 3 and participants in Cohort 2, binary proportions can be estimated to within 16% and 20% with 95% confidence, respectively.

    Time frame: Up to 3 years

06

Study locations

829 sites
  • Veterans Administration Medical Center - Birmingham
    Birmingham, Alabama 35233, United States
  • Anchorage Associates in Radiation Medicine
    Anchorage, Alaska 98508, United States
  • Anchorage Radiation Therapy Center
    Anchorage, Alaska 99504, United States
  • Alaska Breast Care and Surgery LLC
    Anchorage, Alaska 99508, United States
  • Alaska Oncology and Hematology LLC
    Anchorage, Alaska 99508, United States
  • Alaska Women's Cancer Care
    Anchorage, Alaska 99508, United States
  • Anchorage Oncology Centre
    Anchorage, Alaska 99508, United States
  • Katmai Oncology Group
    Anchorage, Alaska 99508, United States
  • Providence Alaska Medical Center
    Anchorage, Alaska 99508, United States
  • Fairbanks Memorial Hospital
    Fairbanks, Alaska 99701, United States
  • Kingman Regional Medical Center
    Kingman, Arizona 86401, United States
  • Cancer Center at Saint Joseph's
    Phoenix, Arizona 85004, United States
  • Banner University Medical Center - Tucson
    Tucson, Arizona 85719, United States
  • University of Arizona Cancer Center-North Campus
    Tucson, Arizona 85719, United States
  • Mercy Hospital Fort Smith
    Fort Smith, Arkansas 72903, United States
  • CHI Saint Vincent Cancer Center Hot Springs
    Hot Springs, Arkansas 71913, United States
  • NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
    Jonesboro, Arkansas 72401, United States
  • University of Arkansas for Medical Sciences
    Little Rock, Arkansas 72205, United States
  • Kaiser Permanente-Anaheim
    Anaheim, California 92806, United States
  • Mission Hope Medical Oncology - Arroyo Grande
    Arroyo Grande, California 93420, United States
  • PCR Oncology
    Arroyo Grande, California 93420, United States
  • Sutter Auburn Faith Hospital
    Auburn, California 95602, United States
  • Sutter Cancer Centers Radiation Oncology Services-Auburn
    Auburn, California 95603, United States
  • Kaiser Permanente-Baldwin Park
    Baldwin Park, California 91706, United States
  • Kaiser Permanente-Bellflower
    Bellflower, California 90706, United States
  • Alta Bates Summit Medical Center-Herrick Campus
    Berkeley, California 94704, United States
  • Tower Cancer Research Foundation
    Beverly Hills, California 90211, United States
  • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    Burbank, California 91505, United States
  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    Cameron Park, California 95682, United States
  • Eden Hospital Medical Center
    Castro Valley, California 94546, United States
  • Sutter Davis Hospital
    Davis, California 95616, United States
  • City of Hope Comprehensive Cancer Center
    Duarte, California 91010, United States
  • Kaiser Permanente-Fontana
    Fontana, California 92335, United States
  • Palo Alto Medical Foundation-Fremont
    Fremont, California 94538, United States
  • Kaiser Permanente-Fresno
    Fresno, California 93720, United States
  • Kaiser Permanente South Bay
    Harbor City, California 90710, United States
  • Kaiser Permanente-Irvine
    Irvine, California 92618, United States
  • UC San Diego Moores Cancer Center
    La Jolla, California 92093, United States
  • Tibor Rubin VA Medical Center
    Long Beach, California 90822, United States
  • Kaiser Permanente Los Angeles Medical Center
    Los Angeles, California 90027, United States
  • Kaiser Permanente West Los Angeles
    Los Angeles, California 90034, United States
  • Cedars Sinai Medical Center
    Los Angeles, California 90048, United States
  • Fremont - Rideout Cancer Center
    Marysville, California 95901, United States
  • Memorial Medical Center
    Modesto, California 95355, United States
  • Palo Alto Medical Foundation-Camino Division
    Mountain View, California 94040, United States
  • Palo Alto Medical Foundation-Gynecologic Oncology
    Mountain View, California 94040, United States
  • Kaiser Permanente-Oakland
    Oakland, California 94611, United States
  • Kaiser Permanente-Ontario
    Ontario, California 91761, United States
  • Palo Alto Medical Foundation Health Care
    Palo Alto, California 94301, United States
  • Stanford Cancer Institute Palo Alto
    Palo Alto, California 94304, United States
  • Kaiser Permanente - Panorama City
    Panorama City, California 91402, United States
  • Eisenhower Medical Center
    Rancho Mirage, California 92270, United States
  • Kaiser Permanente-Riverside
    Riverside, California 92505, United States
  • Kaiser Permanente-Roseville
    Roseville, California 95661, United States
  • Sutter Cancer Centers Radiation Oncology Services-Roseville
    Roseville, California 95661, United States
  • Sutter Roseville Medical Center
    Roseville, California 95661, United States
  • Kaiser Permanente Downtown Commons
    Sacramento, California 95814, United States
  • Sutter Medical Center Sacramento
    Sacramento, California 95816, United States
  • University of California Davis Comprehensive Cancer Center
    Sacramento, California 95817, United States
  • Kaiser Permanente-San Diego Mission
    San Diego, California 92108, United States
  • Kaiser Permanente-San Diego Zion
    San Diego, California 92120, United States
  • California Pacific Medical Center-Pacific Campus
    San Francisco, California 94115, United States
  • Kaiser Permanente-San Francisco
    San Francisco, California 94115, United States
  • Veterans Affairs Medical Center - San Francisco
    San Francisco, California 94121, United States
  • Kaiser Permanente-Santa Teresa-San Jose
    San Jose, California 95119, United States
  • Kaiser Permanente San Leandro
    San Leandro, California 94577, United States
  • Pacific Central Coast Health Center-San Luis Obispo
    San Luis Obispo, California 93401, United States
  • Kaiser Permanente-San Marcos
    San Marcos, California 92078, United States
  • Mills Health Center
    San Mateo, California 94401, United States
  • Kaiser San Rafael-Gallinas
    San Rafael, California 94903, United States
  • Kaiser Permanente Medical Center - Santa Clara
    Santa Clara, California 95051, United States
  • Palo Alto Medical Foundation-Santa Cruz
    Santa Cruz, California 95065, United States
  • Mission Hope Medical Oncology - Santa Maria
    Santa Maria, California 93444, United States
  • Sutter Pacific Medical Foundation
    Santa Rosa, California 95403, United States
  • Kaiser Permanente-South San Francisco
    South San Francisco, California 94080, United States
  • Saint Helena Hospital
    St. Helena, California 94574, United States
  • Palo Alto Medical Foundation-Sunnyvale
    Sunnyvale, California 94086, United States
  • Cedars-Sinai Cancer - Tarzana
    Tarzana, California 91356, United States
  • Torrance Memorial Physician Network - Cancer Care
    Torrance, California 90505, United States
  • Gene Upshaw Memorial Tahoe Forest Cancer Center
    Truckee, California 96161, United States
  • City of Hope Upland
    Upland, California 91786, United States
  • Kaiser Permanente-Vallejo
    Vallejo, California 94589, United States
  • Sutter Solano Medical Center/Cancer Center
    Vallejo, California 94589, United States
  • Kaiser Permanente-Walnut Creek
    Walnut Creek, California 94596, United States
  • Presbyterian Intercommunity Hospital
    Whittier, California 90602, United States
  • Kaiser Permanente-Woodland Hills
    Woodland Hills, California 91367, United States
  • Rocky Mountain Cancer Centers-Aurora
    Aurora, Colorado 80012, United States
  • The Medical Center of Aurora
    Aurora, Colorado 80012, United States
  • Boulder Community Foothills Hospital
    Boulder, Colorado 80303, United States
  • Rocky Mountain Cancer Centers-Boulder
    Boulder, Colorado 80304, United States
  • Rocky Mountain Cancer Centers - Centennial
    Centennial, Colorado 80112, United States
  • Penrose-Saint Francis Healthcare
    Colorado Springs, Colorado 80907, United States
  • Rocky Mountain Cancer Centers-Penrose
    Colorado Springs, Colorado 80907, United States
  • The Women's Imaging Center
    Denver, Colorado 80209, United States
  • AdventHealth Porter
    Denver, Colorado 80210, United States
  • Colorado Blood Cancer Institute
    Denver, Colorado 80218, United States
  • Presbyterian - Saint Lukes Medical Center - Health One
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers-Midtown
    Denver, Colorado 80218, United States
  • Rocky Mountain Cancer Centers-Rose
    Denver, Colorado 80220, United States
  • Rose Medical Center
    Denver, Colorado 80220, United States

Showing the first 100 of 829 sites across 2 countries.

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Registry details

Key details

Study ID
NCT04625647
Lead sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Nov 12, 2020
Start date
Apr 16, 2021
Primary completion
Dec 31, 2026 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Dec 5, 2025

Study contacts

Sukhmani K Padda
principal investigator · SWOG Cancer Research Network

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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