Investigators reported positive topline findings from the phase 3 RATIONALE 306 trial, assessing the first-line combination of tislelizumab and chemotherapy in previously untreated unresectable, locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma.
The phase 3 RATIONALE 306 trial (NCT03783442) assessing first-line tislelizumab and chemotherapy in patients with previously untreated unresectable, locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC), yielded positive topline interim data regardless of PD-L1 expression, according to Novartis.1
Findings from the study indicated that treatment with the combination of tislelizumab and chemotherapy resulted in a statistically significant improvement in overall survival compared with chemotherapy alone. These results will be submitted to regulatory authorities and presented at an upcoming medical meeting.
“People living with esophageal cancer experience painful everyday challenges and typically have a poor prognosis, with a 5-year survival rate of around 5% for metastatic cases, underscoring the urgency for more immunotherapy options,” Jeff Legos, executive vice president of Global Head of Oncology & Hematology Development at Novartis, said in a press release. “We plan to discuss these data with health authorities, and we will continue to expand our tislelizumab clinical development program in pursuit of novel, synergistic combinations with the ultimate goal of extending survival for more patients.”
The multi-regional, placebo-controlled, double-blind trial enrolled approximately 649 patients who were randomized 1:1 to receive tislelizumab plus chemotherapy or chemotherapy alone. The experimental regimen consisted of 3-week cycles of 60 mg/m2 to 80 mg/m2 of intravenous (IV) cisplatin on day 1; 1000 mg/m2 of oral capecitabine on days 1 to 14; 175 mg/m2 of IV paclitaxel on day 1; 750 mg/m2 to 800 mg/m2 of IV fluorouracil on days 1 to 5; 30 mg/m2 of IV oxaliplatin on day 1; and 200 mg of IV tislelizumab. The control group received a matched chemotherapy backbone plus placebo.
The study’s primary end points were progression-free survival and overall survival, with key secondary end points including objective response rate, duration of response, health-related quality of life, and safety.
To enroll on the trial, patients were required to have pathologically confirmed ESCC and stage IV unresectable disease at diagnosis. Those who received palliative radiation within 4 weeks, prior systemic therapy, and prior anti–PD-1 or –PD-L1/2 agents were not included in the study.
The FDA accepted a biologics license application for tislelizumab as treatment for patients with unresectable recurrent, locally advanced, or metastatic ESCC following previous treatment with other systemic therapies.2