KEY TAKEAWAYS
- Phase 2 of the EXCLAIM extension cohort aimed at studying the safety and efficacy of the drug TAK-788 (Mobocertinib) and investigating it as a potential cancer treatment of solid tumors and hematological cancers.
- Patients were given a daily dose of Mobocertinib (160mg) orally for a median duration of 6.8 months.
- At median FU of 13 months, the patients reported improvements in symptoms such as dyspnea, cough, and chest pain and worsening of others such as diarrhea and dry skin.
- Overall, Mobocertinib was found to be clinically significant in improving the symptoms and maintaining the quality of life in patients previously treated for metastatic non-small cell lung cancer.
In the extension cohort of the Phase 1/2 EXCLAIM study, a tyrosine kinase inhibitor (TKI), Mobocertinib aka TAK-788, was given orally to target the epidermal growth factor receptor (EGFR) exon 20 insertions (ex20ins) in 90 patients who were previously treated for EGFR ex20ins+ mNSLC (metastatic non-small cell lung cancer). One dose of 160mg Mobocertinib was given daily in 28-day cycles.
The Patient-Reported Outcomes (PRO) were assessed based on multiple European Organisation for Research and Treatment of Cancer Core Quality-of-Life Questionnaires (EORTC QLQs), including PRO-CTCAE and lung cancer module (QLQ-LC13). The treatment duration was in the range of 0-18.8 months, with a median of 6.8 months. Median FU was 13 months (range 0.7-18.8 months), and the data cutoff date was 1st November 2020.
The patients reported improvements in lung cancer symptoms, such as dyspnea, cough, and chest pain, in the EORTC QLQ-LC13. These improvements were evident during the 2nd cycle of the treatment and lasted throughout the duration of the treatment. The least-squares mean [LSM] changes from baseline for the symptoms of dyspnea was -3.2 [p = 0.019] with improvements in 54.4% of the patients; cough, -9.3 [p < 0.001] with improvements in 46.7% of the patients; and chest pain, -8.2 [p < 0.001] with the symptom improving in 38.9% of the patients. Insomnia and constipation among patients also showed improvements.
However, there no significant changes in the quality of life or global health status of the patients were reported in the EORTC QLQ-LC13 (LSM change from baseline: -1.8 [p = 0.235]). The common side effects were appetite loss, diarrhea, rashes, and dry skin. There was a worsening of diarrhea and appetite loss from the baseline on the symptom scores, with an LSM change from baseline: +34.1; p < 0.001 and +6.6; p = 0.004, respectively. 67.8% of patients worsening dry skin, while 64.4% reported worsening frequency of diarrhea.
Overall, the study achieved durable responses and demonstrated that TAK-788 is clinically meaningful in improving lung cancer-related symptoms. Even with some symptoms worsening, the quality of life in terms of health was maintained throughout the trial.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9821270/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02716116
Citation: Garcia Campelo, M. R., Zhou, C., Ramalingam, S. S., Lin, H. M., Kim, T. M., Riely, G. J., Mekhail, T., Nguyen, D., Goodman, E., Mehta, M., Popat, S., & Jänne, P. A. (2022). Mobocertinib (TAK-788) in EGFR Exon 20 Insertion+ Metastatic NSCLC: Patient-Reported Outcomes from EXCLAIM Extension Cohort. Journal of clinical medicine, 12(1), 112. https://doi.org/10.3390/jcm12010112
