# KEYNOTE-355

Source: https://onco.cc/trials/keynote-355/  
OnCo record `keynote-355` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Established immunotherapy plus chemotherapy as first-line treatment for metastatic triple-negative breast cancer with PD-L1 expression.

## Summary

KEYNOTE-355, trial NCT02819518 sponsored by Merck and published in the New England Journal of Medicine in 2022, established pembrolizumab plus chemotherapy as first-line treatment for metastatic triple-negative breast cancer with PD-L1 expression. It randomised 847 patients and met its primary progression-free and overall survival endpoints in tumours with a combined positive score of ten or more, with no benefit below that threshold, which defined the PD-L1 cut-off used today. OnCo links it to triple-negative breast cancer, pembrolizumab, the CPS term, the TNBC roadmap and IMpassion131. It is now being succeeded by ADC-based first-line regimens such as ASCENT-04, and whether chemotherapy remains part of first-line treatment at all is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-04
- Registry id: NCT02819518
- Phase: 3
- Setting: First-line metastatic TNBC: pembrolizumab + chemotherapy vs chemotherapy
- Sponsor: Merck
- Enrolled: 882
- Result: OS HR 0.73 in CPS ≥10.
- Outcomes: Overall survival, PD-L1 CPS ≥10: Pembrolizumab + chemotherapy 23 months vs Placebo + chemotherapy 16.1 months, HR 0.73; Progression-free survival, PD-L1 CPS ≥10: Pembrolizumab + chemotherapy 9.7 months vs Placebo + chemotherapy 5.6 months, HR 0.66; Overall survival, CPS ≥1: Pembrolizumab + chemotherapy 17.6 months vs Placebo + chemotherapy 16 months, HR 0.86
- Replication: Consistent direction with IMpassion130 (atezolizumab, PD-L1+); IMpassion131 was negative, so the PD-L1 CPS ≥10 population and the chemotherapy partner matter. Now being superseded by ADC + pembrolizumab (ASCENT-04).

## Notes

- Design (Lancet 2020): 847 patients randomised 2 to 1 to pembrolizumab or placebo with nab-paclitaxel, paclitaxel or gemcitabine and carboplatin at 209 sites in 29 countries; the registry figure of 882 includes the 32-patient part 1 safety run-in. Progression-free survival in CPS 10 or more 9.7 versus 5.6 months (hazard ratio 0.65); final overall survival (NEJM 2022) 23.0 versus 16.1 months in CPS 10 or more (hazard ratio 0.73, p 0.0185), 17.6 versus 16.0 in CPS 1 or more (0.86, not significant) and 17.2 versus 15.5 overall (0.89, not tested). Grade 3 to 5 treatment-related adverse events 68.1 versus 66.9 percent.
- UK access: NICE TA801 (29 June 2022) limits the regimen to CPS 10 or more with immune-cell staining below 1 percent, because atezolizumab with nab-paclitaxel (TA639) is commissioned for the immune-cell-positive group.

## Sources

- ClinicalTrials.gov NCT02819518: https://clinicaltrials.gov/study/NCT02819518
- KEYNOTE-355 progression-free survival (Lancet 2020): https://doi.org/10.1016/S0140-6736(20)32531-9
- KEYNOTE-355 overall survival (NEJM 2022): https://doi.org/10.1056/NEJMoa2202809
- NICE TA801 (29 June 2022): https://www.nice.org.uk/guidance/ta801

## Connected records

- cancers: [Immunomodulatory triple-negative breast cancer (IM)](https://onco.cc/cancers/tnbc-immunomodulatory/), [Metastatic triple-negative breast cancer](https://onco.cc/cancers/tnbc-metastatic/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- terms: [Combined positive score (CPS)](https://onco.cc/terms/cps/), [PD-L1 assay discordance (SP142, SP263 and 22C3 in breast cancer)](https://onco.cc/terms/pd-l1-assay-discordance/), [PD-L1 combined positive score 10 in triple-negative breast cancer](https://onco.cc/terms/pd-l1-cps-10-tnbc/)
- trials: [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/), [IMpassion130](https://onco.cc/trials/impassion130/), [IMpassion131](https://onco.cc/trials/impassion131/), [KEYNOTE-119](https://onco.cc/trials/keynote-119/), [TROPION-Breast05](https://onco.cc/trials/tropion-breast05/)
- key papers: [Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms](https://onco.cc/key-papers/paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023/), [ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer](https://onco.cc/key-papers/paper-esmo-metastatic-breast-cancer-guideline-ann-oncol-2021/), [KEYNOTE-355: pembrolizumab plus chemotherapy for PD-L1-positive advanced triple-negative breast cancer](https://onco.cc/key-papers/paper-keynote-355-nejm-2022/), [PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/), [Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial](https://onco.cc/key-papers/paper-keynote-355-lancet-2020/)
- roadmaps: [TNBC roadmap: from 'nothing to target' to ADC + immunotherapy first line](https://onco.cc/roadmaps/tnbc-history/), [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- ideas: [Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance](https://onco.cc/ideas/idea-tnbc-pd-l1-assay-harmonisation/)

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