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A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
A tumour-agnostic, or tissue-agnostic, approval allows a drug to be used for any cancer carrying a specific molecular feature, regardless of the organ in which it started. Examples are Pembrolizumab for MSI-H disease in 2017 and TMB-high disease in 2020, larotrectinib, entrectinib and repotrectinib for NTRK fusions, Dabrafenib + trametinib for BRAF V600E, Selpercatinib for RET, and Trastuzumab deruxtecan for HER2 IHC 3+ tumours in 2024. Such approvals rest on basket trials and broad genomic testing, which is why DESTINY-PanTumor02 and DESTINY-CRC02 are linked. The term is referenced by the Non-small-cell lung cancer, Colorectal, Biliary tract, Endometrial and Cervical cancer entries and by the bottleneck on rare and paediatric cancers without markets.
Backbone ribbon from PDB 5DK3. RCSB PDB 5DK3. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
Showing the molecule this term concerns: Pembrolizumab.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Every KRAS wild-type pancreatic cancer should be tested for NRG1 fusions because a specific, approved antibody now exists; zenocutuzumab is the first targeted drug approved for a pancreatic cancer driver.
Every pancreatic cancer should be tested for mismatch repair deficiency because the 1 percent who have it can receive pembrolizumab, but responses in pancreatic cancer are less frequent and less durable than in other MSI-high cancers.
Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).
It put a number on how rare NRG1 fusions are and showed that heterogeneous partners make RNA-based testing the only reliable way to find them, which is the practical argument for adding a fusion panel to a driver-negative lung cancer work-up.
It is the argument for sequencing every man with advanced prostate cancer rather than only the ones who look high risk: the phenotype is uncommon, it is invisible clinically, it opens the only durable immunotherapy route in this disease, and in one man in five it also identifies Lynch syndrome in the family.
NTRK fusions are under 0.5% of pancreatic cancers but carry a tumour-agnostic approval; this case is the published proof that the label applies here.
This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.
It gave the second PD-1 antibody a colorectal indication in mismatch repair deficient disease and, with the ipilimumab cohort that followed, set up CheckMate 8HW and the first-line combination.
Shares Detection of NRG1 gene fusions in solid tumors, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, Develop drugs in children first when the target is a children's target, RET fusion and RET mutation.
Shares HER2 and genomic testing for biliary cancer on the NHS, A standard for tumour-agnostic approvals: minimum histologies and hierarchical modelling, WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers, KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer.
Shares KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer, Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142), Prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade, Microsatellite-unstable (MSI-high) gastric cancer.
Shares Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion, eNRGy: efficacy of zenocutuzumab in NRG1 fusion-positive cancer, BRAF V600E mutation, Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026).
Shares KEYNOTE-158, Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma), MyPathway, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval.
Shares KEYNOTE-158: pembrolizumab in non-colorectal high microsatellite instability or mismatch repair-deficient cancer, KEYNOTE-158, Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026), Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval.
Shares RET fusion and RET mutation, NTRK1/2/3 gene fusion, Larotrectinib, NTRK.
Shares Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142), Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ.