Dataset Information

National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH).

ABSTRACT: Over the past decade, multiple trials, including the precision medicine trial National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH, 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 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. Although 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. Although NCI-MATCH was histology agnostic with selected tumor exclusions, ComboMATCH has histology-specific and histology-agnostic arms. Although 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.

SUBMITTER: Meric-Bernstam F

PROVIDER: S-EPMC10102840 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH).

Meric-Bernstam Funda F Ford James M JM O'Dwyer Peter J PJ Shapiro Geoffrey I GI McShane Lisa M LM Freidlin Boris B O'Cearbhaill Roisin E RE George Suzanne S Glade-Bender Julia J Lyman Gary H GH Tricoli James V JV Patton David D Hamilton Stanley R SR Gray Robert J RJ Hawkins Douglas S DS Ramineni Bhanumati B Flaherty Keith T KT Grivas Petros P Yap Timothy A TA Berlin Jordan J Doroshow James H JH Harris Lyndsay N LN Moscow Jeffrey A JA

Clinical cancer research : an official journal of the American Association for Cancer Research 20230401 8

Over the past decade, multiple trials, including the precision medicine trial National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH, 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, ...[more]

PMID: 36662819

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Project description:PurposeTherapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols.Patients and methodsTumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with NGS and selected immunohistochemistry in a master screening protocol. The treatment-assignment rate to treatment arms was assessed. Molecular alterations in seven tumors profiled in both NCI-MATCH trial and The Cancer Genome Atlas (TCGA) of primary tumors were compared.ResultsMolecular profiling was successful in 93.0% of specimens. An actionable alteration was found in 37.6%. After applying clinical and molecular exclusion criteria, 17.8% were assigned (26.4% could have been assigned if all subprotocols were available simultaneously). Eleven subprotocols reached their accrual goal as of this report. Actionability rates differed among histologies (eg, > 35% for urothelial cancers and < 6% for pancreatic and small-cell lung cancer). Multiple actionable or resistance-conferring tumor mutations were seen in 11.9% and 71.3% of specimens, respectively. Known resistance mutations to targeted therapies were numerically more frequent in NCI-MATCH than TCGA tumors, but not markedly so.ConclusionWe demonstrated feasibility of screening large numbers of patients at numerous accruing sites in a complex trial to test investigational therapies for moderately frequent molecular targets. Co-occurring resistance mutations were common and endorse investigation of combination targeted-therapy regimens.

Project description:BackgroundA digital dashboard can be an invaluable resource for the research community and can help analyze and visualize data as per the inputs provided by the user. In India, large data sets on malaria are available though presently no digital dashboard is being used to monitor and analyze the malaria data.MethodsWe have developed a dashboard (National Institute of Malaria Research-Malaria Dashboard (NIMR-MDB)) in R software using 19 different packages within which shiny and ggplot2 are used more intensively. NIMR-MDB can be used offline by running the app on any R software installed computer. Furthermore, NIMR-MDB can be accessed across different computers within an organization using a local server, or it may be made publicly available by publishing it online with secured access. There are two options for publishing the shiny dashboard online 1) via a personal Linux server for hosting this application or 2) by hosting the application on a certified online platform such as 'shinyapps.io' at a reasonable cost without setting up a server.FindingsThe NIMR-MDB is a versatile interface that allows prompt and interactive analyses of malaria epidemiological data. The primary interface of NIMR-MDB is like a web page with 14 tabs (or pages) where each Tab corresponds to a particular set of analysis. Users may move from one Tab to another via icons. Each Tab allows flexibility in correlating various epidemiological parameters like SPR, API, AFI, ABER, RT, malaria cases, deaths, BSC and BSE. The malaria epidemiological data can be analyzed in the required granularity (national level, state level or district level), and its enhanced visualization allows for facile usage and extensive analysis.InterpretationThis NIMR-MDB developed here will play an important role in the analysis of epidemiological data and in strategizing malaria control in India. Researchers and policymakers may use it as a prototype for developing other dashboards for various diseases globally.FundingThere is no specific grant received from any funding agency for this work yet.

Dataset Information

National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH).

Publications

National Cancer Institute Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH).

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