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Bending the Curve Trial by Trial
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RATIONALE-305

Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma

Phase 3N = 997NCT03777657

Population
Adults with HER2-negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of PD-L1 expression, who had not received systemic anticancer therapy for advanced disease.
Design
Randomised double-blind placebo-controlled phase 3 trial at 146 centres across Asia, Europe and North America. Patients were randomly assigned 1:1 to tislelizumab 200 mg or placebo every 3 weeks with investigator's choice of oxaliplatin plus capecitabine or cisplatin plus fluorouracil; stratified by region, PD-L1 expression, presence of peritoneal metastases and chemotherapy choice. Primary endpoint: overall survival in patients with a PD-L1 tumour area positivity score (TAP score) of 5% or more and in all randomised patients.
Primary endpoint
OS
Arms
  • Placebo plus chemotherapy (control, n = 496): Placebo with oxaliplatin plus capecitabine or cisplatin plus fluorouracil
  • Tislelizumab plus chemotherapy (experimental, n = 501): Tislelizumab 200 mg every 3 weeks with the same chemotherapy
People
Qiu MZ, RATIONALE-305 Investigators
OSHR 0.74 (95% CI 0.59–0.94)Δ median OS+4.6 monthsOSHR 0.80 (95% CI 0.70–0.92)Δ median OS+2.1 months
Show the numbers
Results reported for RATIONALE-305
EndpointAnalysisTislelizumab plus chemotherapyPlacebo plus chemotherapyEffect
OSPD-L1 TAP score 5% or moreinterimQiu 2024median 17.2 monthsmedian 12.6 monthsHR 0.74 (95% CI 0.59–0.94)P=0.006Interim analysis, as labelled in the abstract.
OSAll randomised patientsfinalQiu 2024median 15 monthsmedian 12.9 monthsHR 0.80 (95% CI 0.70–0.92)P=0.001Final analysis, as labelled in the abstract.
Results reported for RATIONALE-305
EndpointAnalysisTislelizumab plus chemotherapyPlacebo plus chemotherapyEffect
OSPD-L1 TAP score 5% or moreinterimQiu 2024median 17.2 monthsmedian 12.6 monthsHR 0.74 (95% CI 0.59–0.94)P=0.006Interim analysis, as labelled in the abstract.
OSAll randomised patientsfinalQiu 2024median 15 monthsmedian 12.9 monthsHR 0.80 (95% CI 0.70–0.92)P=0.001Final analysis, as labelled in the abstract.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.740.59–0.94
OS0.80.7–0.92
Illustrative — modelled from reported values, not trial data. OS, interim.
0%25%50%75%100%010203040Months (modelled)
  • Tislelizumab plus chemotherapy (experimental)
  • Placebo plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTislelizumab plus chemotherapyPlacebo plus chemotherapy
0100.0%100.0%
1164.2%54.6%
2241.2%29.8%
3227.5%17.2%
4317.7%9.4%
Illustrative — modelled from reported values, not trial data. OS, final.
0%25%50%75%100%0102030Months (modelled)
  • Tislelizumab plus chemotherapy (experimental)
  • Placebo plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTislelizumab plus chemotherapyPlacebo plus chemotherapy
0100.0%100.0%
966.0%61.7%
1941.6%36.0%
2827.4%22.2%
3817.3%13.0%
Primary publication: Qiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ. 2024;385:e078876. PubMedDOI

Appears in

Sources

  1. Qiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ. 2024;385:e078876.

    PubMedDOI