European Commission Approves Tislelizumab for Three Indications in Non-Small Cell Lung Cancer
In April, the European Commission (EC) approved tislelizumab as a treatment for non-small cell lung cancer (NSCLC) across three indications, including first- and second-line use.
The newly-approved indications for tislelizumab are:
- 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 who have metastatic disease.
- In combination with pemetrexed and platinum-containing chemotherapy for the first-line treatment of adult patients with non-squamous NSCLC whose tumors have PD-L1 expression ≥50% 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 who have metastatic disease.
- As 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.
“Non-small cell lung cancer 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,” said Luis Paz-Ares, MD, PhD, Head of the Medical Oncology Service at the Hospital Universitario 12 de Octubre, Madrid. “Across three phase III studies, tislelizumab has been shown to improve outcomes for patients with certain types of NSCLC, providing a new option for those facing the disease.”
The EC approval is based on the results from three phase III studies in the RATIONALE program that enrolled 1,499 patients:
- RATIONALE 307 is an open-label, randomized phase III trial that enrolled 360 patients with advanced 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 (PFS), as well as higher objective response rates and a manageable safety/tolerability profile, regardless of PD-L1 expression. Full study results were published in JAMA Oncology.
- RATIONALE 304 is an open-label, randomized phase III trial that enrolled 334 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 PFS compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]) along with higher response rates and longer response duration. Full study results were published in the Journal of Thoracic Oncology.
- RATIONALE 303 is an open-label, randomized phase III trial with tislelizumab versus docetaxel that enrolled 805 patients with advanced NSCLC who progressed on prior platinum-based chemotherapy. The study 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]), regardless of PD-L1 expression. The full study results were published in the Journal of Thoracic Oncology.
US FDA Grants Breakthrough Therapy Designation to Sunvozertinib for the First-Line Treatment of advanced NSCLC with EGFR Exon 20 Insertion Mutations
On April 7, Shanghai-based biopharmaceutical company Dizal announced the US Food and Drug Administration (FDA) granted a Breakthrough Therapy Designation (BTD) for sunvozertinib for the first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion (Exon20ins) mutations.
According to a statement, the designation was based on results from the global multi-center phase I/II WU-KONG1 study, which evaluated the efficacy and safety of single agent sunvozertinib. The primary study results, which were presented during the 2023 European Society of Medical Oncology Congress, demonstrated an objective response rate (ORR) of 78.6% and a median progression-free survival (mPFS) of 12.4 months.
Sunvozertinib was previously granted BTDs by the FDA and the China Center for Drug Evaluation (CDE) for relapsed or refractory patients. The drug was subsequently approved in China in 2023 for the treatment of patients who progressed after first-line treatment. According to the company, new drug applications in that setting are expected to be filed in the US and European Union later this year.
Breakthrough Therapy Designations are intended to expedite the development and regulatory review of drugs for serious or life-threatening conditions. To qualify, new drugs must demonstrate promising preliminary clinical results indicating substantial improvement on clinically significant endpoints compared to existing treatments. Drugs designated as breakthrough therapies benefit accelerated development policies.
