Request for Applications: Pediatric Oncology Concepts for ComboMATCH-COG

The Children’s Oncology Group is collaborating with the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and the National Cancer Institute (NCI) to develop the NCI-ComboMATCH, a biomarker-driven, precision medicine trial to follow the NCI-COG Pediatric MATCH. The NCI-ComboMATCH will concentrate on targeted drug combination signal-seeking studies supported by preclinical in vivo evidence. Each cooperative research group in the NCI Clinical Trials Network (NCTN), including the COG, will administratively manage a cassette of subprotocols. Treatment assignment will occur through the NCI-ComboMATCH Master Protocol.

The COG is seeking high-level concepts for consideration for further development and presentation to the NCI-ComboMATCH Agents and Genes Working Group (C-AGWG). Initial review of potential pediatric proposals will be carried out by the COG Combination Agent Prioritization and Selection Committee (CAPS). Concept proposals can be submitted to the CAPS using the COG ComboMATCH Concept Sheet. Investigators will be invited to present supportive data and a preliminary proposal to CAPS prior to formal concept development and submission.

The NCI-ComboMATCH prioritizes concepts supported by patient-derived xenograft (PDX) and cell-line-derived xenograft (CDX) data to test the hypothesis that in vivo preclinical evidence can be used to predict the benefit of drug combination therapy in well-characterized patient populations. The brief scientific principles are as follows:

  • Sub-protocol proposals must be supported by both a strong scientific rationale and in vivo evidence of efficacy.
  • Combination therapy proposals are desired. There should be evidence that both agents in the combination are required for efficacy; that the combination is at least additive and preferably synergistic.
  • Selected monotherapy arms can be considered for agents with strong rationale or preliminary signal of efficacy.
  • The proposed agents should have safety data available or justification of why a short run-in design may be appropriate.
  • Combinations involving immunotherapy agents are discouraged.

Additional information regarding the NCI-ComboMATCH trial can be found at