image: Lead investigator Kristen R. Spencer, DO, MPH, a medical oncologist at New York University's Langone Perlmutter Cancer Center and chair of the ECOG-ACRIN Genomics Subcommittee.
Credit: NYU LANGONE Staff
Another ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) treatment trial is open as part of the ComboMATCH precision medicine study platform. ComboMATCH-E5 is evaluating treatment for patients with KRAS G12C-mutated advanced solid tumors with two different targeted drugs given together. The two drugs include the KRAS G12C inhibitor sotorasib and panitumumab, a human monoclonal antibody antagonist specific to the epidermal growth factor receptor (EGFR). Each drug is approved by the US Food and Drug Administration (FDA) as single-agent therapy for particular cancer types.
"Given the preclinical data demonstrating EGFR over-dependency as a mechanism of resistance to KRAS G12C inhibition, a trial is warranted to evaluate the combination in patients experiencing resistance to prior KRAS G12C inhibition therapy," said lead investigator Kristen R. Spencer, DO, MPH, a medical oncologist at New York University's Langone Perlmutter Cancer Center and chair of the ECOG-ACRIN Genomics Subcommittee.
Meanwhile, data from the recently reported phase 3 CodeBreak 300 trial (NCT05198934) show that the combination of sotorasib and panitumumab had promising efficacy and safety in patients with KRAS G12C-mutated advanced colorectal cancer.1
"The CodeBreak 300 data place the combination of sotorasib and panitumumab in prime position for a randomized study of the combination, which we will compare to sotorasib monotherapy across advanced solid tumor types," said Dr. Spencer.
ComboMATCH-E5 aims to enroll 105 adults with KRAS G12C-mutated solid tumors that have progressed on at least one prior therapy. Accrual will be limited to 15 patients in each solid tumor type to ensure that the trial includes multiple types of cancer. The design is as follows:
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Patients who have never received treatment with a KRAS G12C inhibitor drug will be randomized 1:1 to Group 1 or 2. Patients in Group 1 will take sotorasib as a once-daily pill for 28 days and have panitumumab administered intravenously on days 1 and 15 of each 28-day cycle. Patients in Group 2 will receive sotorasib only.
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Those who have previously received a KRAS G12C inhibitor drug will be assigned to Group 3 and receive sotorasib and panitumumab. Patients in Group 2 who have progressed on sotorasib alone will be eligible to switch to Group 3 and receive the combination.
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Patients with lung or colorectal cancer are excluded from Groups 1 and 2 due to the availability of FDA-approved treatments. However, those who have progressed on the FDA-approved treatment may be eligible for Group 3.
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Treatment will continue until disease progression or intolerable toxicity. Tumor imaging reassessment will occur every 8 weeks. The trial's primary endpoints are progression-free survival (Groups 1 and 2) and the overall response rate (Group 3).
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To take part in this trial, patients must first enroll in the ComboMATCH registration trial to help determine eligibility.
"If this trial is successful, the positive results would be a strong signal that the combination should move on to a larger randomized phase 3 trial for confirmation outside of ComboMATCH," said co-investigator Dustin A. Deming, MD, a medical oncologist at the University of Wisconsin Carbone Cancer Center and chair of the ECOG-ACRIN Developmental Therapeutics Committee.
ComboMATCH Treatment Trial E5: A Randomized Phase II Study of AMG 510 (Sotorasib) with or without Panitumumab in Advanced Solid Tumors (NCT05638295) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health. Amgen, the manufacturer of sotorasib and panitumumab, is supplying the drugs under a Cooperative Research and Development Agreement (CRADA) with the NCI.
Visit ecog-acrin.org for ComboMATCH-E5 details and participating trial locations.
About ComboMATCH
ComboMATCH (Molecular Analysis for Combination Therapy Choice) is a large precision medicine initiative evaluating new anti-cancer drug combinations in select groups of adults and children with cancer. It aims to identify new genetically matched drug combinations due to growing evidence, shown in the landmark NCI-MATCH trial and other recent studies, that drug combinations may be more effective than single drugs. ECOG-ACRIN and the NCI are co-leading the initiative, which contains a growing number of treatment trials by the Alliance for Clinical Trials in Oncology, Children's Oncology Group, ECOG-ACRIN, NRG Oncology, and SWOG Cancer Research Network—all members of the NCI's National Clinical Trials Network (NCTN). The first ECOG-ACRIN trial in ComboMATCH opened in July 2023.
About ECOG-ACRIN
The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is an expansive membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. The Group comprises nearly 1400 member institutions and 21,000 research professionals in the United States and around the world. ECOG-ACRIN is known for advancing precision medicine and biomarker research through its leadership of major national clinical trials integrating cutting-edge genomic approaches. Member researchers and advocates collaborate across more than 40 scientific committees to design studies spanning the cancer care spectrum, from early detection to management of advanced disease. ECOG-ACRIN is funded primarily by the National Cancer Institute, part of the National Institutes of Health. Follow us on Twitter/ X @eaonc, Facebook, LinkedIn, and Instagram, or call 215.789.3631.
Citation
1. Fakih MG, Salvatore L, Esaki T et al. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. doi: 10.1056/NEJMoa2308795. Epub 2023 Oct 22.