Pyrotinib combined with thalidomide in advanced non-small-cell lung cancer patients harboring HER2 exon 20 insertions (PRIDE): protocol of an open-label, single-arm phase II trial
| Autor: | Xinghao Ai, Ziming Li, Zhiwei Chen, Hong Jian, Zhen Zhou, Zheng-bo Song, Shun Lu, Yongfeng Yu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Oncology
Diarrhea Cancer Research medicine.medical_specialty Antibody-drug conjugate Human epidermal growth factor receptor 2 China Lung Neoplasms Receptor ErbB-2 Afatinib Angiogenesis Inhibitors Drug Administration Schedule chemistry.chemical_compound Study Protocol Ikaros Transcription Factor Trastuzumab Internal medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Genetics medicine Protocol Humans Lung cancer Protein Kinase Inhibitors RC254-282 Acrylamides business.industry Neoplasms. Tumors. Oncology. Including cancer and carcinogens Exons Pyrotinib medicine.disease Dacomitinib Thalidomide chemistry Trastuzumab emtansine Neratinib Mutation Aminoquinolines business Non-small-cell lung cancer medicine.drug |
| Zdroj: | BMC Cancer BMC Cancer, Vol 21, Iss 1, Pp 1-7 (2021) |
| ISSN: | 1471-2407 |
| Popis: | Background Standard therapy for human epidermal growth factor receptor 2 (HER2)-mutant non-small-cell lung cancer (NSCLC) is lacking. The clinical benefits with pan-HER inhibitors (afatinib, neratinib, and dacomitinib), anti-HER2 antibody drug conjugate (ADC) trastuzumab emtansine, and an emerging irreversible tyrosine kinase inhibitor (TKI) poziotinib were modest. Another new ADC trastuzumab deruxtecan showed encouraging outcomes, but only phase I study was completed. Pyrotinib, another emerging irreversible epidermal growth factor receptor (EGFR)/HER2 dual TKI, has been approved in HER2-positive breast cancer in 2018 in China. It has shown promising antitumor activity against HER2-mutant NSCLC in phase II trials, but pyrotinib-related diarrhea remains an issue. The antiangiogenic and immunomodulatory drug thalidomide is a cereblon-based molecular glue that can induce the degradation of the IKAROS family transcription factors IKZF1 and IKZF3. The use of thalidomide can also decrease gastrointestinal toxicity induced by anti-cancer therapy. Methods This is an open-label, single-arm phase II trial. A total of 39 advanced NSCLC patients with HER2 exon 20 insertions and ≤ 2 lines of prior chemotherapy will be recruited, including treatment-naïve patients who refuse chemotherapy. Patients are allowed to have prior therapy with immune checkpoint inhibitors and/or antiangiogenic agents. Those who have prior HER2-targeting therapy or other gene alterations with available targeted drugs are excluded. Eligible patients will receive oral pyrotinib 400 mg once daily and oral thalidomide 200 mg once daily until disease progression or intolerable toxicity. The primary endpoint is objective response rate. Discussion The addition of thalidomide to pyrotinib is expected to increase the clinical benefit in advanced NSCLC patients with HER2 exon 20 insertions, and reduce the incidence of pyrotinib-related diarrhea. We believe thalidomide is the stone that can hit two birds. Trial registration ClinicalTrials.gov Identifier: NCT04382300. Registered on May 11, 2020. |
| Databáze: | OpenAIRE |
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