Tislelizumab Plus Chemo Receives Positive CHMP Opinion for ES-SCLC

Tislelizumab Plus Chemotherapy in ES-SCLC

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The European Medicines Agency’s Committee for Medicinal Products for Human Use has issued a positive opinion recommending the approval of tislelizumab (Tevimbra) in combination with etoposide and platinum chemotherapy for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).1

The recommendation was supported by data from the phase 3 RATIONALE-312 trial (NCT04005716), which showed that at a median follow-up of 14.2 months (interquartile range, 8.6-25.3), patients treated with the combination of tislelizumab and chemotherapy (n = 227) achieved a median overall survival (OS) of 15.5 months (95% CI, 13.5-17.1) compared with 13.5 months (95% CI, 12.1-14.9) for those given placebo plus chemotherapy (n = 230; HR, 0.75; 95% CI, 0.61-0.93; 1-sided P = .0040).2

“The aggressive nature of ES-SCLC makes it an extremely difficult type of lung cancer to treat, and currently available treatments may not adequately control disease progression,” Silvia Novello, MD, PhD, president of Women Against Lung Cancer in Europe (WALCE) and head of the Medical Oncology Unit of San Luigi Hospital in Orbassano, Italy, stated in a news release.1 “The compelling data from the RATIONALE-312 study demonstrates the potential of [tislelizumab] plus chemotherapy as a further first-line treatment option to extend OS for patients with ES-SCLC.”

The randomized, double-blind, placebo-controlled, multicenter phase 3 trial enrolled patients at least 18 years of age with histologically or cytologically confirmed ES-SCLC that was stage IV, was T3 or T4, or had tumor or nodal volume too large to be encompassed in a tolerable irradiation plan.2 No prior treatment for ES-SCLC was permitted. Other key inclusion criteria consisted of an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ function.

Investigators excluded patients who had active leptomeningeal disease or uncontrolled, untreated brain metastasis; those with a mixed histologic diagnosis, such as SCLC and adenocarcinoma; patients with underlying medical conditions that could affect the study drug; and patients who received previous treatments targeting the immune checkpoint pathways.

Patients were randomly assigned 1:1 to receive 200 mg of tislelizumab or placebo once every 3 weeks in combination with 100 mg/m2 of etoposide on days 1 to 3 of each 21-day cycle and 75 mg/m2 of cisplatin or area under the curve 5 of carboplatin on day 1 of each cycle. Chemotherapy was given for 4 cycles, and patients then continued with tislelizumab or placebo alone once every 3 weeks. Treatment continued until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent.

OS served as the trial’s primary end point. Secondary end points included progression-free survival (PFS), overall response rate (ORR), duration of response, disease control rate, and safety.

Additional data showed that the estimated 1-, 2-, and 3-year OS rates were 63%, 33%, and 25%, respectively, in the tislelizumab arm. These respective rates were 58%, 22%, and 9% in the placebo arm.

Tislelizumab plus chemotherapy generated a median PFS of 4.7 months (95% CI, 4.3-5.5) compared with 4.3 months (95% CI, 4.2-4.4) for placebo plus chemotherapy (HR, 0.64; 95% CI, 0.52-0.78; 1-sided P < .0001). The respective ORRs were 68% (95% CI, 62%-74%) and 62% (95% CI, 55%-68%).

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in more than 99% of patients in both arms. The rates of grade 3 or higher TRAEs were 85% for the tislelizumab arm (n = 227) vs 86% for the placebo arm.

The most common any-grade TRAEs were alopecia (tislelizumab arm, 78%; placebo arm, 79%), anemia (76%; 79%), neutropenia (69%; 70%), decreased white blood cell count (56%; 65%), thrombocytopenia (49%; 52%), nausea (41%; 41%), leukopenia (33%; 24%), decreased appetite (32%; 33%), increased alanine aminotransferase levels (26%; 17%), constipation (22%; 12%), decreased neutrophil count (22%; 24%), vomiting (21%; 21%), increased aspartate aminotransferase levels (19%; 13%), decreased platelet count (13%; 15%), hypothyroidism (13%; 4%), rash (12%; 8%), malaise (11%; 10%), hypoalbuminemia (11%; 7%), fatigue (10%; 5%), hyponatremia (10%; 6%), and decreased lymphocyte count (10%; 10%).

TRAEs led to treatment discontinuation in 11% of patients in the tislelizumab arm vs 2% of patients in the placebo arm.

References

1. BeiGene receives positive CHMP opinion for Tevimbra as a first-line treatment for extensive-stage small cell lung cancer. News release. BeiGene. March 31, 2025. Accessed March 31, 2025. https://ir.beigene.com/news/beigene-receives-positive-chmp-opinion-for-tevimbra-as-a-first-line-treatment-for-extensive-stage-small-cell/4ce3b472-213b-4eea-9457-8a63b381d7df/
2. Cheng Y, Fan Y, Zhao Y, et al. Tislelizumab plus platinum and etoposide versus placebo plus platinum and etoposide as first-line treatment for extensive-stage SCLC (RATIONALE-312): a multicenter, double-blind, placebo-controlled, randomized, phase 3 clinical trial. J Thorac Oncol. 2024;19(7):1073-1085. doi:10.1016/j.jtho.2024.03.008