Tislelizumab Earns European Approval in Non–Small Cell Lung Cancer

Supporting data for approval came from the phase 3 RATIONALE 307 trial (NCT03594747), the phase 3 RATIONALE 304 trial (NCT03663205), and the phase 3 RATIONALE 303 trial (NCT03358875), which collectively included 1499 patients with NSCLC.

The European Commission has approved tislelizumab (Tizveni) as a treatment for patients with non–small cell lung cancer (NSCLC) in the frontline or second-line setting, according to a press release from developers BeiGene, Ltd.¹

Specifically, the agent has received approval as a treatment in combination with carboplatin and either paclitaxel or nab-paclitaxel as frontline therapy for adults with squamous NSCLC and locally advanced disease who are not suitable to receive surgery and platinum-containing chemoradiation or those who have metastatic disease.

Additionally, the European Commission approved tislelizumab plus pemetrexed and platinum-based chemotherapy as frontline therapy for adults with metastatic disease or those with nonsquamous histology, PD-L1 expression in at least 50% of tumor cells, no EGFR or ALK mutations, and locally advanced disease who are not candidates to receive surgery or platinum-containing chemoradiotherapy.

The agent is also approved as monotherapy for adult patients with locally advanced or metastatic NSCLC following prior platinum-based treatment; those with EGFR mutations or ALK-positive disease may receive tislelizumab following treatment with prior targeted therapies.

The press release noted the developers plan to combine the indication for NSCLC with second-line esophageal squamous cell carcinoma under the brand name Tevimbra. This will be available in the European Union later in 2024.

“[NSCLC] remains one of the most common and deadly cancers in Europe, with 50% of patients diagnosed already progressed to advanced stages, making it difficult to treat,” Luis Paz-Ares, MD, PhD, head of the Medical Oncology Service at the Hospital Universitario 12 de Octubre, Madrid, said in the press release.¹ “Across 3 phase 3 studies, tislelizumab has been shown to improve outcomes for patients with certain types of NSCLC, providing a new option for those [with] the disease.”

Supporting data for approval came from the phase 3 RATIONALE 307 trial (NCT03594747), the phase 3 RATIONALE 304 trial (NCT03663205), and the phase 3 RATIONALE 303 trial (NCT03358875), which collectively included 1499 patients with NSCLC.

RATIONALE 307

In RATIONALE 307, the median progression-free survival (PFS) was 7.6 months (95% CI, 6.0-9.8) with tislelizumab plus carboplatin and paclitaxel in arm A, 7.6 months (95% CI, 5.8-11.0) with tislelizumab in combination with nab-paclitaxel and carboplatin in arm B, and 5.5 months (95% CI, 4.2-5.7) with chemotherapy alone in arm C.² Compared with outcomes observed in arm C, investigators reported that PFS improved with treatment in arm A (HR, 0.524; 95% CI, 0.370-0.742; P <.001) as well as arm B (HR, 0.478; 95% CI, 0.336-0.679; P <.001).

Common grade 3 or higher treatment-emergent adverse effects (TEAEs) included neutrophil level decreases, neutropenia, and leukopenia.

The RATIONALE 307 trial included 360 patients with advanced squamous NSCLC.

RATIONALE 304

Investigators of the RATIONALE 304 trial highlighted that tislelizumab plus carboplatin or cisplatin and pemetrexed produced a median PFS of 9.7 months (95% CI, 7.7-11.5) in arm A compared with 7.6 months (95% CI, 5.6-8.0) in those who received platinum-containing chemotherapy plus pemetrexed alone in arm B (HR, 0.645; 95% CI, 0.462-0.902; P = .0044).³ The estimated PFS rates at 12 months were 31.3% (95% CI, 21.7%-41.4%) and 16.7% (95% CI, 6.8%-30.5%) in each respective arm.

Common grade 3 or higher TEAEs were generally associated with chemotherapy and included neutropenia and leukopenia.

The RATIONALE 304 trial included 334 of those with locally advanced or metastatic nonsquamous NSCLC.

RATIONALE 303

As of the final data cutoff analysis date of July 15, 2021, across the intent-to-treat population of the RATIONALE 303 trial, the median overall survival (OS) was 16.9 months (95% CI, 15.2-19.1) with tislelizumab monotherapy and 11.9 months (95% CI, 9.6-13.5) with docetaxel (HR, 0.66; 95% CI, 0.56-0.79).⁴

Pneumonia, anemia, and dyspnea were some of the most common grade 3 or higher TEAEs reported in the trial.

Investigators of the RATIONALE 303 trial included 805 patients with advanced NSCLC and disease progression following previous platinum-containing chemotherapy.

The European Medicine Agency’s Committee for Medicinal Products for Human Use issued a positive opinion in support of tislelizumab and its approval for patients with NSCLC in February 2024.⁵

References

1. BeiGene receives European Commission approval for tislelizumab as treatment for non-small cell lung cancer. News release. BeiGene, Ltd. April 23, 2024. Accessed April 23, 2024. https://tinyurl.com/572rtsz3
2. Wang J, Lu S, Yu X, et al. Tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non–small-cell lung cancer: a phase 3 randomized clinical trial. JAMA Oncol. 2021;7(5):709-717. doi:10.1001/jamaoncol.2021.0366
3. Lu S, Wang J, Yu Y, et al. Tislelizumab plus chemotherapy as first-line treatment for locally advanced or metastatic nonsquamous NSCLC (RATIONALE 304): a randomized phase 3 trial. J Thorac Oncol. 2021;16(9):1512-1522. doi:10.1016/j.jtho.2021.05.005
4. Zhou C, Huang D, Fan Y, et al. Tislelizumab versus docetaxel in patients with previously treated advanced NSCLC (RATIONALE-303): a phase 3, open-label, randomized controlled trial. J Thorac Oncol. 2021;18(1):93-105. doi:10.1016/j.jtho.2022.09.217
5. BeiGene receives positive CHMP opinion for tislelizumab as treatment for non-small cell lung cancer. News release. BeiGene, Ltd. February 26, 2024. Accessed April 23, 2024. http://tinyurl.com/4w9e734t