Tislelizumab Receives Recommendation for European Approval in NSCLC

February 26, 2024

News

Article

Findings from 3 phase 3 trials support the marketing authorization application for tislelizumab as a treatment for patients with non–small cell lung cancer in the European Union.

Supporting data for the marketing authorization application for tislelizumab came from 3 phase 3 trials: the RATIONALE 307 trial (NCT03594747) in patients with advanced squamous NSCLC, the RATIONALE 304 trial (NCT03663205) in those with locally advanced or metastatic nonsquamous NSCLC, and the RATIONALE 303 trial (NCT03358875) in those with previously treated advanced NSCLC.

The European Medicine Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has expressed a positive opinion in support of the approval of tislelizumab (Tevimbra) as a treatment for patients with non–small cell lung cancer (NSCLC), according to a press release from BeiGene, the developers of tislelizumab.¹

The positive CHMP opinion supports tislelizumab as a treatment across 3 NSCLC indications. The first indication is for tislelizumab plus carboplatin and either paclitaxel or nab-paclitaxel as first-line treatment for adult patients with squamous NSCLC and locally advanced disease not suitable to be managed with surgical resection or platinum-containing chemoradiotherapy or metastatic disease.

The second indication is for tislelizumab plus pemetrexed and platinum-containing chemotherapy as a frontline treatment for adult patients with nonsquamous NSCLC with a PD-L1 expression of 50% or higher, with no EGFR/ALK mutations. Patients also had disease that was locally advanced and not suitable for surgical resection or platinum-based chemoradiotherapy or metastatic NSCLC.

The third indication is for tislelizumab as a single agent for adult patients with locally advanced or metastatic disease following previous platinum-containing treatment. If patients had an EGFR/ALK mutation, they should have previously received targeted therapies before tislelizumab.

“Through 3 phase 3 clinical trials enrolling nearly 1500 patients across the world including in the European Union, tislelizumab has been shown to be an effective therapy for patients with treatment-naïve and treatment-resistant NSCLC,” Mark Lanasa, MD, PhD, chief medical officer of solid tumors at BeiGene, said in the press release.¹ “Today's positive CHMP opinion brings us one step closer to providing an important treatment option to patients in Europe with lung cancer, which is among the most common cancers and a leading cause of cancer death in the region.”

RATIONALE 307 Trial

After a median follow-up of 8.6 months (95% CI, 8.1-9.0) in the RATIONALE 307 trial, the median progression-free survival (PFS) was 7.6 months (95% CI, 6.0-9.8) with tislelizumab plus carboplatin and paclitaxel (arm A) and 7.6 months (95% CI, 5.8-11.0) with tislelizumab plus nab-paclitaxel and carboplatin (arm B) compared with 5.5 months (95% CI, 4.2-5.7) with chemotherapy alone (arm C).² The HR for arm A vs arm C was 0.524 (95% CI, 0.370-0.742; P <.001) and 0.478 for arm B vs arm C (95% CI, 0.336-0.679; P <.001).

Overall, 12.5%, 29.7%, and 15.4% of patients discontinued study treatment following adverse effects (AEs) in arm A, arm B, and arm C, respectively. The most common grade 3 or higher toxicity was neutrophil level decreases. Additionally, there were 6 treatment-related AEs resulting in death, although none of these deaths were solely associated with tislelizumab.

RATIONALE 304 Trial

With a median follow-up of 9.8 months (95% CI, 9.23-10.38), in the RATIONALE 304 trial, the median PFS was 9.7 months (95% CI, 7.7-11.5) in patients who received tislelizumab plus carboplatin or cisplatin and pemetrexed (arm A) compared with 7.6 months (95% CI, 5.6-8.0) in those who were treated with platinum-based chemotherapy plus pemetrexed alone (arm B; HR, 0.645; 95% CI, 0.462-0.902; P = .0044).³ The estimated 12-month PFS rates were 31.3% (95% CI, 21.7%-41.4%) vs 16.7% (95% CI, 6.8%-30.5%) in each respective arm.

The most common grade 3 or higher AEs, which were primarily related to chemotherapy, included neutropenia (44.6% vs 35.5%), leukopenia (21.6% vs 14.5%), and thrombocytopenia (19.4% vs 13.6%) in arm A and arm B, respectively. There were treatment-related AEs (TRAEs) leading to death in 3 and 1 from each respective arm, which were all due to pneumonitis.

RATIONALE 303 Trial

In the RATIONALE 303 trial, the median overall survival (OS) was 17.2 months (95% CI, 15.3-20.0) with tislelizumab vs 11.9 months (95% CI, 10.2-13.9) with docetaxel (HR, 0.64; 95% CI, 0.53-0.78; P <.0001).⁴ Additionally, the median OS in each respective arm was 19.1 months (95% CI, 16.8-25.8) vs 11.9 months (95% CI, 8.9-14.0) among patients with a PD-L1 level of 25% or higher (HR, 0.52; 95% CI, 0.38-0.71).

Any-grade treatment-emergent AEs affected 96.8% of patients who received tislelizumab compared with 98.4% of those who received docetaxel. Investigators concluded that there were no new safety signals identified in the trial.

References

BeiGene receives positive CHMP opinion for tislelizumab as treatment for non-small cell lung cancer. News release. BeiGene, Ltd. February 26, 2024. Accessed February 26, 2024. http://tinyurl.com/4w9e734t
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
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
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