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NCI-MATCH was the largest trial to sequence tumours from thousands of patients across the United States and give each a drug matched to the mutation rather than to the organ. It proved the system could work at national scale, found real activity for a handful of matches, and showed that most single drugs given for a single mutation do little.
NCI-MATCH opened in August 2015, run by ECOG-ACRIN for the National Cancer Institute with Keith Flaherty and Peter O'Dwyer as chairs and every NCI cooperative group taking part. Patients whose cancer had progressed on standard therapy, or who had a rare cancer with no standard, had a fresh biopsy sequenced in one of four accredited laboratories with a common assay, and a central rules engine matched alterations to treatment arms, each a single-arm phase 2 with objective response as the endpoint. The trial started with ten arms and grew to nearly 40, testing drugs including dabrafenib with trametinib, nivolumab, trastuzumab emtansine, capivasertib, copanlisib, palbociclib, sunitinib, binimetinib, afatinib, osimertinib, crizotinib, larotrectinib and adavosertib.
The screening results, in the Journal of Clinical Oncology in 2020, described 5,954 patients: sequencing succeeded in the great majority, more than a third had an alteration the trial deemed actionable, and 17.8 percent were assigned to an arm. Rare and less common cancers made up most of the enrolment, which made NCI-MATCH one of the biggest sources of rare-tumour genomics. Among the arms, dabrafenib plus trametinib in BRAF V600-mutant non-melanoma cancers (response rate 38 percent) and nivolumab in mismatch repair-deficient non-colorectal cancers (36 percent) were clearly positive and supported later tumour-agnostic thinking; capivasertib in AKT1-mutant tumours and copanlisib in PIK3CA-mutant tumours showed moderate activity; most arms matching a drug to an amplification, a loss-of-function change or a rarer kinase mutation did not reach their bar. A 2023 Nature Medicine paper drew the lessons together, and a 2024 Clinical Cancer Research analysis showed that activity often depended on tumour type as much as on the mutation.
What NCI-MATCH changed was infrastructure and expectations: a common national assay and rules engine, a precedent for enrolling rare cancers by mutation, and the recognition that genotype-only matching rarely suffices, which led directly to ComboMATCH (combinations chosen from preclinical evidence, opened 2023), myeloMATCH in leukaemia and the iMATCH immunotherapy programme. Its arms continue to be reported as follow-up matures.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
One trial page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
Shares Cancer variant knowledgebases and molecular tumour boards, Master protocol (platform, basket and umbrella trials), Rare cancers, Crizotinib.
Shares Master protocol (platform, basket and umbrella trials), ECOG-ACRIN Cancer Research Group, Crizotinib, Basket, umbrella, and platform trials.
Shares Master protocol (platform, basket and umbrella trials), Capivasertib, Crizotinib, Palbociclib.
Shares Master protocol (platform, basket and umbrella trials), Rare cancers, Basket, umbrella, and platform trials, Rare and paediatric cancers without markets.
Shares Master protocol (platform, basket and umbrella trials), Rare cancers, Tumour-agnostic (tissue-agnostic) approval, Basket, umbrella, and platform trials.
Shares Cancer variant knowledgebases and molecular tumour boards, Master protocol (platform, basket and umbrella trials), Rare cancers, Basket, umbrella, and platform trials.
Shares Dabrafenib, Rare cancers, Trametinib, Tumour-agnostic (tissue-agnostic) approval.
Shares NCI-COG Pediatric MATCH (APEC1621), Dabrafenib, Larotrectinib, Tumour-agnostic (tissue-agnostic) approval.