Tislelizumab Plus Chemoradiotherapy Shows Superior Response Rates in Gastric Cancer Trial
Key Insights
The phase 2b TERRIFIC study demonstrated that adding tislelizumab to chemoradiotherapy achieved a 25.7% pathologic complete response rate compared to 18.2% with chemoradiotherapy alone and 5.3% with chemotherapy alone in gastric cancer (search) patients.
Among patients who underwent surgery, the combination therapy achieved a 32.1% pathologic complete response rate and 67.9% major pathologic response rate, substantially higher than either control arm.
Treatment-related adverse events were manageable across all arms, with grade 3 or higher events occurring in 31.4% of combination therapy patients versus 24.2% and 15.8% in the control groups.
The addition of tislelizumab to neoadjuvant chemoradiotherapy demonstrated superior pathologic response rates compared to standard treatments in patients with locally advanced gastric cancer (search) and gastroesophageal junction adenocarcinoma (search), according to preliminary results from the phase 2b TERRIFIC study presented at the 2026 ASCO Gastrointestinal Cancers Symposium.
Study Design and Patient Population
The multicenter, randomized controlled, open-label trial enrolled patients 18 years and older with histologically confirmed locally advanced gastric cancer (search) or adenocarcinoma of the gastroesophageal junction, AJCC stage III to IVa disease, and an ECOG performance status of 0 or 1. Patients were randomly assigned in a 2:2:1 ratio to receive tislelizumab plus chemoradiotherapy (arm A; n=35), chemoradiotherapy alone (arm B; n=33), or chemotherapy alone (arm C; n=19).
The median ages across the three arms were 63.0, 61.0, and 62.0 years respectively. Most patients had ECOG performance status of 2 (65.7%, 66.7%, and 57.9%), tumors located in the stomach (62.9%, 63.6%, and 63.2%), and TNM stage III disease (65.7%, 63.6%, and 68.4%).
Treatment Protocol
In arm A, patients received 200 mg of intravenous tislelizumab on day 1 of cycle 1, days 1 and 22 of cycle 2, and day 1 of cycle 3 during neoadjuvant treatment, plus adjuvant tislelizumab every 3 weeks. Chemoradiotherapy consisted of 45 Gy via volumetric modulated arc therapy or Tomotherapy, combined with S-1 and oxaliplatin or S-1 plus nab-paclitaxel for 3 cycles. During adjuvant therapy, S-1 was given as maintenance for 3 cycles.
Primary Efficacy Results
Among patients in the intention-to-treat population, pathologic complete response rates were 25.7% in the tislelizumab plus chemoradiotherapy arm, 18.2% in the chemoradiotherapy alone arm, and 5.3% in the chemotherapy alone arm.
In the surgery set, comprising patients who underwent subsequent operations (n=28, 27, and 17 respectively), pathologic complete response rates were even higher: 32.1%, 22.2%, and 5.9% across the three arms.
Major pathologic response rates in the intention-to-treat population were 54.3%, 48.5%, and 15.8% for arms A, B, and C respectively. In the surgery set, major pathologic response rates reached 67.9%, 59.3%, and 17.6%.
Tumor Regression and Surgical Outcomes
Tumor regression grade analysis in the surgery set showed that 32.1% of patients in arm A achieved TRG 0 compared to 22.2% in arm B and 5.9% in arm C. Clinical T downstaging rates were similar across arms (57.1%, 63.0%, and 58.8%), while clinical N downstaging rates were 75.0%, 92.6%, and 70.6% respectively.
Total gastrectomy was the most common surgical method, performed in 78.6%, 77.8%, and 64.7% of patients in each respective arm. The R0 resection rate was 100% across all arms, with median lymph nodes examined ranging from 21 to 30.5 across the groups.
Safety Profile
Treatment-related adverse events of any grade occurred in 77.1% of arm A, 75.8% of arm B, and 57.9% of arm C. Grade 3 or higher treatment-related adverse events occurred in 31.4%, 24.2%, and 15.8% of patients respectively.
Treatment-related adverse events leading to chemotherapy discontinuation were rare, occurring in 2.9%, 3.0%, and 0% of the respective arms. In arms A and B, radiotherapy discontinuation due to adverse events occurred in 8.6% and 3.0% of patients. Immunotherapy discontinuation occurred in 5.7% of arm A patients, with 28.6% experiencing immune-related adverse events, of which 2.9% were grade 3 or higher.
Clinical Significance
"This is the first report of the preliminary analysis evaluating 3 neoadjuvant strategies for locally advanced gastric cancers and [gastroesophageal junction adenocarcinoma (search)]," said lead study author Jia Wei, MD, PhD, of the Comprehensive Cancer Center of the Nanjing Drum Tower Hospital at Nanjing University (search). "Our results show that the combination with the PD-1 (search) [inhibitor] and CRT have a higher pCR rate when compared with CRT or chemotherapy alone."
The study's primary endpoint was pathologic complete response rate in the intention-to-treat population, with secondary endpoints including pathologic complete response in the surgery set, major pathologic response rates, objective response rate, disease control rate, safety, and 2-year event-free survival and overall survival rates.
Wei noted that "[adverse] effects are manageable and the survival data are still ongoing. Also, we [will be] doing a biomarker analysis in the future."