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)
18 Years and older, Male and Female
S1900E (primary)
S1900E
NCI-2020-08103
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.
Objectives
PRIMARY OBJECTIVE:
I. To evaluate the response rate (confirmed, complete or partial) of sotorasib (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.
V. To establish a tissue/blood repository from participants with refractory NSCLC.
OUTLINE:
Patients receive sotorasib 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.
Eligibility
- 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 symptomatic brain metastases must have received local treatment to these metastases and remained clinically controlled and asymptomatic for at least 3 days following stereotactic radiation and/or 14 days following whole brain radiation, and prior to sub-study registration. Participants with untreated asymptomatic brain metastases are eligible
- 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 active pneumonitis requiring treatment with steroids and/or other immunosuppressive therapies. Radiographic evidence of pneumonitis in a radiation field, as long as asymptomatic, is permitted
- 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) >= 1.0 x 10^3/uL obtained within 28 days prior to sub-study registration
- Platelet count >= 75 x 10^3/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 =< 1.5 X institutional upper limit of normal (IULN) within 28 days prior to sub-study registration
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 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 if creatinine > 1.5X IULN, calculated creatinine clearance >= 30 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’ most recent Zubrod performance status must be 0-1 and be 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
- 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
Treatment Sites in Georgia
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
Click here to learn more about clinical trials.