National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH).
Funda Meric-BernstamJames M FordPeter J O'DwyerGeoffrey I ShapiroLisa Meier McShaneBoris FreidlinRoisin E O'CearbhaillSuzanne GeorgeJulia L Glade BenderGary H LymanJames V TricoliDavid R PattonStanley R HamiltonRobert C GrayDouglas S HawkinsBhanumati RamineniKeith T FlahertyPetros D GrivasTimothy Anthony YapJordan D BerlinJames H DoroshowLyndsay N HarrisJeffrey A MoscowPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2023)
Over the past decade, multiple trials, including the precision medicine trial NCI-MATCH (National Cancer Institute-Molecular Analysis for Therapy Choice, EAY131, NCT02465060) have sought to determine if treating cancer based on specific genomic alterations is effective, irrespective of the cancer histology. Although many therapies are now approved for the treatment of cancers harboring specific genomic alterations, most patients do not respond to therapies targeting a single alteration. Further, when antitumor responses do occur, they are often not durable due to the development of drug resistance. Therefore, there is a great need to identify rational combination therapies that may be more effective. To address this need, the National Cancer Institute (NCI) and National Clinical Trials Network have developed NCI-ComboMATCH, the successor to NCI-MATCH. Like the original trial, NCI-ComboMATCH is a signal-seeking study. The goal of ComboMATCH is to overcome drug resistance to single-agent therapy and/or utilize novel synergies to increase efficacy by developing genomically-directed combination therapies, supported by strong preclinical in vivo evidence. While NCI-MATCH was mainly comprised of multiple single-arm studies, NCI-ComboMATCH tests combination therapy, evaluating both combination of targeted agents as well as combinations of targeted therapy with chemotherapy. While NCI-MATCH was histology agnostic with selected tumor exclusions, ComboMATCH has histology-specific and histology-agnostic arms. While NCI-MATCH consisted of single arm studies, ComboMATCH utilizes single-arm as well as randomized designs. NCI-MATCH had a separate, parallel Pediatric MATCH trial, whereas ComboMATCH will include children within the same trial. We present rationale, scientific principles, study design and logistics supporting the ComboMATCH study.
Keyphrases
- combination therapy
- phase iii
- clinical trial
- phase ii
- study protocol
- open label
- end stage renal disease
- double blind
- papillary thyroid
- chronic kidney disease
- mental health
- randomized controlled trial
- stem cells
- placebo controlled
- squamous cell carcinoma
- high throughput
- peritoneal dialysis
- childhood cancer
- case control
- bone marrow
- locally advanced