# RATIONALE-306

Source: https://onco.cc/trials/rationale-306/  
OnCo record `rationale-306` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

RATIONALE-306 is the trial behind tislelizumab's US approval for squamous oesophageal cancer, with the biggest gains in PD-L1-positive tumours.

## Summary

RATIONALE-306, trial NCT03783442 sponsored by BeOne, formerly BeiGene, and reported in 2022, is the trial behind tislelizumab's US approval for first-line advanced oesophageal squamous cell carcinoma, with the biggest gains in PD-L1-positive tumours. It randomised 649 patients to tislelizumab or placebo with platinum chemotherapy and met its primary overall survival endpoint in all patients, published in Lancet Oncology in 2023, with a larger effect in PD-L1-positive disease; the FDA approved it on 4 March 2025 restricted to PD-L1 tumour area positivity of one percent or more, and the EU approved it in 2024. OnCo links it to oesophageal cancer, PD-1 as a target and tislelizumab, and the result is consistent with KEYNOTE-590, CheckMate 648 and ESCORT-1st. Whether a fifth PD-1 antibody in this setting competes on price rather than data is the practical question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03783442
- Phase: 3
- Setting: First-line advanced oesophageal squamous cell carcinoma: tislelizumab + platinum chemotherapy vs placebo + chemotherapy
- Sponsor: BeOne (BeiGene)
- Enrolled: 649
- Result: OS 17.2 vs 10.6 months (HR 0.66); PD-L1 ≥1% OS 16.8 vs 9.6 months.
- Outcomes: Overall survival, all patients: Tislelizumab + chemotherapy 17.2 months vs Placebo + chemotherapy 10.6 months, HR 0.66; Overall survival, PD-L1 ≥1%: Tislelizumab + chemotherapy 16.8 months vs Placebo + chemotherapy 9.6 months
- Replication: Consistent with KEYNOTE-590, CheckMate 648, ESCORT-1st.

## Sources

- ClinicalTrials.gov NCT03783442: https://clinicaltrials.gov/study/NCT03783442

## Connected records

- cancers: [Oesophageal cancer](https://onco.cc/cancers/esophageal/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Tislelizumab](https://onco.cc/drugs/tislelizumab/)
- companies: [BeOne Medicines (formerly BeiGene)](https://onco.cc/companies/beone/)

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