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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
105
Undergo tumor biopsy
Undergo collection of blood
Undergo CT scan
Undergo MRI
Given IV
Given PO
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
RECRUITINGUniversity of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
RECRUITINGThe Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, United States
RECRUITINGCedars Sinai Medical Center
Los Angeles, California, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At 6 and 12 months, assessed up to 3 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
VA Palo Alto Health Care System
Palo Alto, California, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
RECRUITINGUM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, United States
RECRUITING...and 171 more locations