Trastuzumab Emtansine in HER2+ Recurrent Metastatic Non-Small-Cell Lung Cancer: Study Protocol
Kadoaki Ohashi1, Katsuyuki Hotta2, Taizo Hirata2
1Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan.
Abstract:
The treatment outcome has been unsatisfactory for patients with non-small-cell lung cancer (NSCLC) refractory to standard first-line chemotherapy. Trastuzumab emtansine (T-DM1), an anti-HER2 antibody conjugated with a vinca alkaloid, has been approved for clinical use in HER2+ breast cancer in many countries. Approximately 5% of NSCLC tumors possess HER2 alterations, and T-DM1 has shown excellent antitumor effects against HER2+ lung cancer cell lines in preclinical models. Therefore, we hypothesized that T-DM1 could significantly inhibit the growth of HER2+ lung cancers. We have launched a nonrandomized phase II trial of T-DM1 monotherapy for patients with HER2+ lung cancers. The major eligibility criteria are as follows: age ≥ 20 years, pathologically diagnosed NSCLC with documented HER2 positivity (immunohistochemistry 3+, both immunohistochemistry 2+ and fluorescence in situ hybridization positive, or exon 20 insertion mutation), and previous chemotherapy. Thirty patients will receive T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint is the overall response rate. This trial will provide information on whether T-DM1 monotherapy is effective against HER2+ lung cancer.
Insights
Trastuzumab emtansine (T-DM1) is being investigated as a novel treatment for patients with HER2-positive non-small-cell lung cancer (NSCLC) who have not responded to chemotherapy. This phase II trial assesses T-DM1
Area of Science:
- Oncology
- Pharmacology
- Genetics
Background:
- Non-small-cell lung cancer (NSCLC) often shows unsatisfactory treatment outcomes in patients refractory to standard first-line chemotherapy.
- Trastuzumab emtansine (T-DM1), an antibody-drug conjugate targeting HER2, is approved for HER2-positive breast cancer.
- Approximately 5% of NSCLC tumors exhibit HER2 alterations, presenting a potential therapeutic target.
Purpose of the Study:
- To evaluate the efficacy of T-DM1 monotherapy in patients with HER2-positive NSCLC.
- To hypothesize that T-DM1 can significantly inhibit the growth of HER2-positive lung cancers.
- To provide data on the effectiveness of T-DM1 for this patient population.
Main Methods:
- A nonrandomized phase II clinical trial was initiated.
- Participants are patients with pathologically diagnosed NSCLC and documented HER2 positivity (IHC 3+, IHC 2+/FISH+, or exon 20 insertion mutation) who have received prior chemotherapy.
- Thirty patients will receive T-DM1 at a dose of 3.6 mg/kg every 3 weeks, with overall response rate as the primary endpoint.
Main Results:
- This section is to be filled once the trial concludes and results are available.
Conclusions:
- This trial aims to determine if T-DM1 monotherapy is an effective treatment option for HER2-positive NSCLC.
- The study will offer crucial insights into the therapeutic potential of T-DM1 in a previously untreated NSCLC subgroup.
