National Cancer Institute Launches Precision Medicine Initiative

On June 1, 2023, the National Cancer Institute (NCI), a subset of the NIH, launched ComboMATCH, a precision medicine initiative for cancer patients. ComboMATCH — short for Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice — uses an individual patient’s tumor biology to determine the appropriate drug combination for treatment.

The initiative will be a series of phase II clinical trials that test various drug combinations based on tumor biology. Some trials will evaluate two targeted drugs, while others will analyze the efficacy of a tumor drug and chemotherapy drug approach.

These studies will build on data collected during the NCI-MATCH clinical trial, which used genetic mutations to determine the appropriate drug monotherapy. However, the study revealed that patients quickly became resistant to a single drug, indicating a need for combination therapy.

“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,” said Jeffrey Moscow, MD, of the Investigational Drug Branch in NCI’s Division of Cancer Treatment and Diagnosis and a co-leader of ComboMATCH, in the NIH press release.

The NCI will collaborate with trial groups in the National Clinical Trials Network (NCTN), including the Alliance for Clinical Trials in Oncology, Children’s Oncology Group, ECOG-ACRIN Cancer Research Group, NRG Oncology, and the SWOG Cancer Research Network.

The clinical trials will vary in enrollment, with some enrolling patients with specific cancer types and others enrolling regardless of kind. The drug types will also vary, as some will combine FDA-approved drugs, and others will incorporate FDA-approved drugs with investigational drugs.

Any provider in a participating community hospital or cancer center may refer a patient to the study for further evaluation depending on their cancer type and genetic makeup of the cancer cells. Additionally, researchers across the 35 labs doing genomic testing for this study will be able to refer patients. Upon trial math, patients must have a tumor biopsy for genetic profiling.

To date, there are already three ComboMATCH trials up and running, including a study testing fulvestrant and binimetinib for patients with an NF1 mutation in hormone receptor-positive breast cancer that has spread; a trial combining selumetinib and olaparib for women with a RAS mutation who have endometrial or ovarian cancer that has come back or persists despite treatment; and ipatasertib with chemotherapy for patients with solid tumors that have AKT mutations.

“An important strength of the study is that the combinations being evaluated in ComboMATCH will be based on preclinical data showing that indeed the combination is better than either agent alone, as well as safety data from phase 1 studies,” said James Ford, MD, of Stanford University School of Medicine, a co-leader of ComboMATCH and lead investigator on the coordination effort by ECOG-ACRIN, in the release. "There will be agreement among all the NCTN trial group representatives to evaluate each combination.”  

Beyond the three up-and-running trials, the NCI plans six additional trials and anticipates more trials throughout the initiative. Additionally, the organization hopes to launch two other initiatives: ImmunoMATCH and MyeloMATCH. The studies will evaluate immunotherapy and treatments for acute myeloid leukemia or myelodysplastic syndromes, respectively, using genetic data.