NCI launches new initiative to test new drug combinations that target specific tumor alterations

The National Cancer Institute (NCI), a division of the National Institutes of Health, has embarked on a significant precision medicine cancer initiative to evaluate the effectiveness of treating both adults and children with innovative drug combinations that specifically target tumor alterations. This groundbreaking initiative, known as the Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH), represents the largest endeavor of its kind, focusing on the examination of cancer drug combinations guided by tumor biology. The primary objective of ComboMATCH is to identify promising treatments that can progress to larger and more definitive clinical trials beyond the scope of this platform.

ComboMATCH comprises multiple phase 2 treatment trials, each assessing the efficacy of a distinct drug combination, usually involving either two targeted drugs or a combination of a targeted drug and chemotherapy. Some trials will encompass patients with specific alterations in their cancer cells, regardless of the primary cancer location, while others will target patients with specific cancer types.

According to Dr. James H. Doroshow, Director of NCI's Division of Cancer Treatment and Diagnosis, the majority of treatments currently administered to patients are not determined by genomic information. However, with ComboMATCH, the aim is to demonstrate that genomic abnormalities can be utilized to determine the most effective treatment combinations for individual patients.

''With ComboMATCH, we're hoping that by attacking both the genetic driver and the mechanisms of resistance, we will obtain more durable clinical responses and more benefit to patients."

ComboMATCH (NCT05564377) is a collaborative effort involving the NCI and all five U.S. clinical trial groups within the NCI's National Clinical Trials Network (NCTN). It serves as the successor to NCI-MATCH, a pioneering precision medicine clinical trial. In NCI-MATCH, patients were assigned treatment based on genetic changes in their tumors rather than the type of cancer. While NCI-MATCH primarily evaluated single drugs targeting the specific mutation driving tumor growth in patients, the emergence of resistance to these single-agent therapies became evident in many cases. To address this challenge, ComboMATCH will explore combinations of both U.S. Food and Drug Administration-approved drugs and investigational agents provided by pharmaceutical companies. The vast number of potential drug combinations poses the challenge of narrowing down and prioritizing the most promising ones.

The ECOG-ACRIN Cancer Research Group leads the overarching coordination effort of ComboMATCH. All five U.S. NCTN groups, including the Alliance for Clinical Trials in Oncology, Children's Oncology Group, ECOG-ACRIN Cancer Research Group, NRG Oncology, and SWOG Cancer Research Network, will spearhead the treatment trials within ComboMATCH.

The identification of potential participants for ComboMATCH trials will involve various methods. Genomic testing of tumors has become a standard component of care for individuals with many cancer types. Referrals from doctors at participating community hospitals and cancer centers can lead to additional eligibility screenings for patients whose test results exhibit specific alterations investigated in the treatment trials. Moreover, commercial and academic labs conducting genomic testing as part of the standard of care can identify eligible patients for ComboMATCH trials.

Patients matched to a trial will be required to provide a pretreatment tumor biopsy specimen for genomic profiling. This will enable ComboMATCH investigators to delve into additional questions, such as the reasons behind the success or failure of certain treatments.

Currently, three ComboMATCH trials are open for enrollment. These include studies on fulvestrant (Faslodex) and binimetinib (Mektovi) for patients with an NF1 mutation in hormone receptor-positive breast cancer, selumetinib (Koselugo) and olaparib (Lynparza) or selumetinib alone for women with a RAS mutation and endometrial or ovarian cancer that has recurred or persisted despite treatment, and chemotherapy plus ipatasertib for patients with AKT mutations and metastatic solid tumors. Six additional trials will become available in the coming months, with more trials expected to be added over time. NCI plans to include around 2,000 patients in ComboMATCH, but this number may expand.

Unlike its predecessor, MATCH, which excluded children and had a separate trial for pediatric patients called PediatricMATCH, some ComboMATCH trials will include children with cancer.

NCI also intends to launch two additional precision medicine cancer treatment trials: ImmunoMATCH, which aims to improve the response to targeted treatments using immunotherapy by prospectively characterizing the immune status of tumors, and MyeloMATCH, which will assess treatments based on genetic changes in the cancer cells of individuals with acute myeloid leukemia or myelodysplastic syndromes.

Source : NIH/National Cancer Institute