Repotrectinib is Recommended for EU Approval to Treat ROS1-Positive NSCLC
Repotrectinib has been recommended by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use to treat advanced ROS1-positive non-small cell lung cancer (NSCLC) and patients with advanced NTRK fusion-positive solid tumors.1
Repotrectinib was approved by the US Food and Drug Administration in 2023 for the treatment of locally advanced or metastatic ROS1-positive NSCLC. That decision and the EMA recommendation were based on the results of the TRIDENT-1 trial, which enrolled patients with ROS1-positive locally advanced or metastatic NSCLC.2
The trial evaluated 71 patients who were ROS1 TKI-naïve and had received up to one prior line of platinum-based chemotherapy and/or immunotherapy, as well as 56 patients who had received one prior ROS1 TKI without any prior platinum-based chemotherapy or immunotherapy.1
The confirmed objective response rate (ORR) in the ROS1 TKI naïve group was 79%, compared to 38% in patients who had received prior treatment with a ROS1 inhibitor.2 The median DOR was 34 months and 15 months in the two respective cohorts.2
Zenocutuzumab-zbco Becomes the First FDA-Approved Systemic Therapy for Patients with NSCLC or Pancreatic Adenocarcinoma
The FDA recently granted accelerated approval for zenocutuzumab-zbco in December 2024 for patients with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma that harbor an NRG1 gene fusion, following systemic therapy.
The decision is based on findings from the eNRGy trial, which enrolled 64 patients with advanced or metastatic NRG1 fusion-positive NSCLC and 30 patients with advanced or metastatic NRG1 fusion-positive pancreatic adenocarcinoma. All participants had experienced disease progression after receiving standard-of-care treatment.3
The primary efficacy outcome measures were confirmed ORR and DOR.3 For patients with NSCLC, the ORR was 33%, and the median DOR was 7 months.3 For patients with pancreatic adenocarcinoma, the ORR was 40%, with a DOR range of 4 to 17 months.3
Durvalumab Secures FDA Approval for LS-SCLC
Earlier this month, the FDA announced the approval of durvalumab for patients with limited-stage small cell lung cancer (LS-SCLC) whose disease did not progress after receiving concurrent platinum-based chemotherapy and radiation therapy, following the results of the ADRIATIC trial.
The randomized, placebo-controlled trial enrolled 730 patients with LS-SCLC who did not experience disease progression after receiving concurrent platinum-based chemotherapy and radiation therapy.4 Patients were randomized in a 1:1:1 ratio to receive either durvalumab as a single agent, a combination of durvalumab with tremelimumab, or a placebo.4
In the study, durvalumab demonstrated a statistically significant improvement in OS improvement compared to placebo, with a hazard ratio (HR) of 0.73.5 The median OS was 56 months in the durvalumab cohort and 33 months in the placebo group.5
FDA Gives Green Light to Next-Generation Sequencing Test for Patients with NSCLC
FoundationOne Liquid CDx has been approved by the FDA as a companion diagnostic tool for tepotinib. This diagnostic test is specifically designed to identify MET exon 14 skipping alterations in patients with NSCLC.
FoundationOne Liquid CDx is a next-generation sequencing diagnostic test and the first FDA-approved companion diagnostic device specifically designed to identify patients eligible for treatment with tepotinib.
Tepotinib obtained accelerated approval from the FDA in February 2021 for patients with NSCLC. It received traditional approval in February 2024 based on the results of the phase II VISION trial.
The study enrolled 313 patients with metastatic NSCLC harboring MET exon 14 skipping alterations. These patients received tepotinib at a dosage of 450 mg once daily until disease progression or the occurrence of unacceptable toxicity.5
The ORR was 57% among 164 treatment-naïve patients, with 40% of these patients experiencing a duration of response (DOR) of 12 months or longer.5 Among 149 previously treated patients, the ORR was 45%, with 36% of responders achieving a DOR of 12 months or longer.5
Additionally, durvalumab also showed a statistically significant improvement in PFS compared to placebo, with an HR of 0.76.6 The median PFS was nearly 17 months in the durvaluumab cohort, compared to just over 9 months in the placebo group, respectively.6
Resources
- 1. https://www.ema.europa.eu/en/medicines/human/EPAR/augtyro
- 2. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-repotrectinib-ros1-positive-non-small-cell-lung-cancer
- 3. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic
- 4. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-limited-stage-small-cell-lung-cancer?utm_medium=email&utm_source=govdelivery
- 5. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tepotinib-metastatic-non-small-cell-lung-cancer
- 6. Mazieres, Julien et al. “Tepotinib Treatment in Patients With MET Exon 14-Skipping Non-Small Cell Lung Cancer: Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial.” JAMA oncology vol. 9,9 (2023): 1260-1266. doi:10.1001/jamaoncol.2023.1962
