# KEYNOTE-177

Source: https://onco.cc/trials/keynote-177/  
OnCo record `keynote-177` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The trial that made immunotherapy alone, with no chemotherapy, the first treatment for the 5% of bowel cancers with a broken DNA spell-checker. Over half of patients were alive at five years.

## Summary

Pembrolizumab doubled median PFS (16.5 vs 8.2 months, HR 0.60) and at 5-year follow-up (Annals of Oncology 2024) median OS was 77.5 months with a 5-year OS of 54.8%, despite 62% of chemotherapy patients crossing over to anti-PD-1 therapy. First-line FDA approval June 2020. ESMO-MCBS grade 4. The comparator arm's crossover means the OS hazard ratio (0.73) understates the benefit.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT02563002
- Phase: 3
- Setting: First-line MSI-H/dMMR metastatic colorectal cancer: pembrolizumab vs investigator-choice chemotherapy
- Sponsor: Merck
- Enrolled: 307
- Result: PFS 16.5 vs 8.2 months (HR 0.60); 5-year OS 54.8%, median OS 77.5 months.
- Outcomes: Progression-free survival: Pembrolizumab 16.5 months vs Chemotherapy 8.2 months, HR 0.6; Overall survival (5-year follow-up): Pembrolizumab 77.5 months vs Chemotherapy 36.7 months, HR 0.73
- Replication: Consistent with CheckMate 8HW (nivolumab ± ipilimumab) and the earlier single-arm KEYNOTE-164/CheckMate 142 cohorts; the class effect in dMMR CRC is replicated across three antibodies.

## Sources

- ClinicalTrials.gov NCT02563002: https://clinicaltrials.gov/study/NCT02563002
- 5-year follow-up, Annals of Oncology 2024: https://www.annalsofoncology.org/article/S0923-7534(24)04949-4/fulltext

## Connected records

- cancers: [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma](https://onco.cc/cancers/msi-high-pdac/), [Mismatch-repair deficient (MSI-high) colorectal cancer](https://onco.cc/cancers/msi-high-colorectal/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- trials: [CALGB/SWOG 80405](https://onco.cc/trials/calgb-80405/), [CheckMate 142](https://onco.cc/trials/checkmate-142/)
- people: [Thierry André](https://onco.cc/people/thierry-andre/)
- key papers: [KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer](https://onco.cc/key-papers/paper-keynote-177-nejm-2020/), [Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ](https://onco.cc/key-papers/paper-le-mmr-deficiency-pd1-nejm-2015/), [Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval](https://onco.cc/key-papers/paper-le-mmr-deficiency-science-2017/), [Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up](https://onco.cc/key-papers/paper-esmo-metastatic-colorectal-cancer-guideline-ann-oncol-2023/), [Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies](https://onco.cc/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/), [Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study](https://onco.cc/key-papers/paper-keynote-177-lancet-oncol-2022-update/)
- ideas: [Making microsatellite-stable colorectal cancer immunotherapy-responsive](https://onco.cc/ideas/idea-immunotherapy-mss-crc/)
- roadmaps: [Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation](https://onco.cc/roadmaps/colorectal-roadmap/)
- bottlenecks: [Cold tumours and the immunosuppressive microenvironment](https://onco.cc/bottlenecks/b-tme-immunosuppression/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/)

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