Finding studies
Finding studies
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Lead
National Cancer Institute (NCI)
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.
Age
18–any
Sex
ALL
Healthy volunteers
Not accepted
