The monoclonal antibody tislelizumab (brand name Tevimbra) has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for the treatment of non-small cell lung cancer (NSCLC) across three indications, its manufacturer BeiGene has announced.
Tislelizumab has been recommended by the CHMP for use in combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of adult patients with squamous NSCLC who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
The second indication is for use in combination with pemetrexed and platinum-containing chemotherapy for the first-line treatment of adult patients with non-squamous NSCLC whose tumours have PD-L1 expression on ≥50% of tumour cells with no EGFR or ALK positive mutations and who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
Tislelizumab is also recommended as a monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab, the CHMP said.
The positive opinion for these indications is based on the results of three Phase 3 trials which demonstrated the benefit of tislelizumab as a first- and second-line treatment for patients with NSCLC.
Dr Mark Lanasa, chief medical officer, solid tumors at BeiGene, said: ‘Through three Phase 3 clinical trials enrolling nearly 1,500 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.’
He added that the 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.’
Statistically significant tislelizumab trials
The RATIONALE 307 trial looked at first-line tislelizumab in combination with chemotherapy for patients with advanced squamous NSCLC.
It met its primary endpoints with the median progression free survival at 7.7 months for tislelizumab in combination with paclitaxel and carboplatin (hazard ratio, HR: 0.45 [95% CI: 0.326-0.619]; P< 0.001) and 9.6 months for tislelizumab in combination with nab-paclitaxel and carboplatin (HR: 0.43 [95% CI: 0.308-0.60]; P< 0.001).
This was compared to 5.5 months for paclitaxel and carboplatin alone, at a median study follow-up of 8.6 months.
The most common grade ≥3 treatment emergent adverse events were decreased neutrophil levels, neutropenia and leukopenia.
RATIONALE 304 also considered tislelizumab in combination with chemotherapy as first-line treatment and focused on patients with locally advanced or metastatic non-squamous NSCLC.
The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in progression free survival compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]; P=0.0054) along with higher response rates and longer response duration.
The most common grade ≥3 treatment emergent adverse events were associated with chemotherapy and included neutropenia and leukopenia.
Looking at second- and third-line treatment, the RATIONALE 303 trial looked at tislelizumab versus docetaxel in patients with advanced NSCLC who progressed on prior platinum-based chemotherapy.
This trial met its primary endpoint, with second- or third-line tislelizumab resulting in statistically significant and clinically meaningful improvement in overall survival compared with docetaxel in the intent-to-treat population (HR: 0.66 [95% CI: 0.56-0.79]; P<0.0001), regardless of PD-L1 expression.
At the final analysis, overall survival in the PD-L1 positive population was also significantly improved in favour of tislelizumab (median 19.3 vs 11.5 months, respectively; HR: 0.53 [95% CI: 0.41-0.70]; P<0.0001).
The most commonly reported grade ≥3 treatment emergent adverse events were pneumonia, anaemia and dyspnoea.
