# IND.227 / KEYNOTE-483

Source: https://onco.cc/trials/keynote-483/  
OnCo record `keynote-483` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Showed that adding a PD-1 blocker to standard chemotherapy helps in mesothelioma, giving a second immunotherapy-based first-line option.

## Summary

IND.227, also KEYNOTE-483, trial NCT02784171 sponsored by the Canadian Cancer Trials Group with Merck and reported in 2023, showed that adding pembrolizumab to platinum and pemetrexed helps in unresectable pleural mesothelioma, giving a second immunotherapy-based first-line option. It randomised 440 patients, met its primary overall survival endpoint with a modest effect and a much higher response rate, with benefit again concentrated in non-epithelioid disease, and led to FDA approval on 17 September 2024; it was an academic-led trial with industry drug supply. OnCo links it to mesothelioma, pembrolizumab, pemetrexed, the epithelioid versus sarcomatoid term and the histology pairing; DREAM supported it in phase 2, but the DREAM3R phase 3 was stopped early and BEAT-meso missed survival. Whether the modest benefit holds up outside non-epithelioid disease is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT02784171
- Phase: 2/3
- Setting: Unresectable pleural mesothelioma, first line: pembrolizumab + platinum-pemetrexed vs platinum-pemetrexed
- Sponsor: Canadian Cancer Trials Group / Merck
- Enrolled: 440
- Result: OS 17.3 vs 16.1 months, HR 0.79; ORR 52% vs 29%.
- Outcomes: Overall survival: Pembrolizumab + chemotherapy 17.3 months vs Chemotherapy 16.1 months, HR 0.79; Objective response rate: Pembrolizumab + chemotherapy 52% vs Chemotherapy 29%
- Replication: Supported by DREAM (phase 2, durvalumab + chemotherapy) but DREAM3R phase 3 was stopped early; BEAT-meso (atezolizumab + bevacizumab + chemotherapy) missed OS.

## Sources

- ClinicalTrials.gov NCT02784171: https://clinicaltrials.gov/study/NCT02784171
- Merck OS announcement: https://www.merck.com/news/keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-overall-survival-versus-chemotherapy-alone-as-first-line-treatment-for-advanced-malignant-pleural-mesothelioma/

## Connected records

- cancers: [Mesothelioma](https://onco.cc/cancers/mesothelioma/), [Pleural mesothelioma](https://onco.cc/cancers/pleural-mesothelioma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Pemetrexed](https://onco.cc/drugs/pemetrexed/)
- companies: [Canadian Cancer Trials Group (CCTG)](https://onco.cc/companies/cctg/)
- terms: [Epithelioid vs sarcomatoid (biphasic) mesothelioma](https://onco.cc/terms/epithelioid-vs-sarcomatoid/)
- pairings: [Histology → first-line choice in mesothelioma](https://onco.cc/pairings/histology-directs-first-line-meso/)
- key papers: [KEYNOTE-483 (CCTG IND.227): pembrolizumab plus chemotherapy versus chemotherapy in untreated pleural mesothelioma](https://onco.cc/key-papers/paper-keynote-483-lancet-2023/)

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