Single-center study to determine the safety and efficacy of CT-707 in Chinese patients with advanced anaplastic lymphoma kinase-rearranged non-small-cell lung cancer

Our plain-English summary of Single-center study to determine the safety and efficacy of CT-707 in Chinese patients with advanced anaplastic lymphoma kinase-rearranged non-small-cell lung cancer, by P. Song, X. Zhang, D. Yang, et al (Thoracic Cancer, 2020).

The study

• Authors: P. Song, X. Zhang, D. Yang, H. Wang, X. Si, L. Zhang
• Journal: Thoracic Cancer
• Published: 2020;11(5):1216-1223
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: It has been proven that ALK-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitors while the chemotherapy resistance is unavoidable. In this study, safety and antitumor activity of the novel ALK inhibitor (ALKi) CT-707 were evaluated in Chinese patients with advanced ALK-rearranged NSCLC.

Methods: This single-center, open-label phase I study recruited adult patients with ALK-rearrangement (confirmed by fluorescence in situ hybridization and/or immunohistochemistry) of locally advanced/metastatic malignancies including NSCLC. This study consisted of two parts: dose escalation and dose expansion. CT-707 was administered orally once a day for 21 days.

Results: A total of 13 patients who were treated with CT-707 from 450 to 600 mg (in the dose increasing phase) were enrolled in this trial (two patients were previously treated with crizotinib). There were 12 patients diagnosed with lung adenocarcinoma and one patient with malignant pleural mesothelioma. After treatment, grade 3 diarrhea (600 mg once a day) was found as dose-limiting toxicity (DLT).The most common adverse events included diarrhea (92%), elevated aspartate aminotransferase (61%), elevated alanine aminotransferase (54%), hair loss (38%), and vomiting (31%). The overall response rate was 77% (10/13). Among all patients, four of the five patients who did not receive any treatment, one of the two patients who had received treatments with crizotinib, and five of the six patients who received standard chemotherapy achieved partial response (PR). One patient reached a complete remission (CR).

Conclusions: This study indicated that CT-707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose-expansion phase recruitment has started.

© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

In plain English

This single-center, open-label phase I trial was run at Peking Union Medical College Hospital, China. It tested CT-707, an experimental oral ALK-targeting drug, in adults with advanced ALK-rearranged cancers. Thirteen patients were treated in the dose-escalation stage: 12 had lung adenocarcinoma and one had malignant pleural mesothelioma. Doses were 450 mg once a day (7 patients), 300 mg twice a day (2) or 600 mg once a day (4). The study did not look at asbestos exposure. Overall, 10 of 13 (77%) had a complete or partial tumor response and 11 of 13 (85%) had disease control. The mesothelioma patient (600 mg group) progressed after one cycle and died of tumor progression. All patients had at least one drug-related side effect, most often diarrhea (92%). One section reported one dose-limiting toxicity, grade 3 diarrhea at 600 mg, but another also recorded drug-induced liver injury as a dose-limiting toxicity. Median progression-free survival was 13 months (95% confidence interval 9.98 to 16.00). The authors concluded that CT-707 is effective and has a reliable safety profile. They noted that only two crizotinib-resistant patients with brain metastases were included.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Single-center, open-label phase I drug trial (dose-escalation stage reported)
• Who was studied: 13 adult Chinese patients with advanced ALK-rearranged tumors treated at Peking Union Medical College Hospital: 12 with lung adenocarcinoma and 1 with malignant pleural mesothelioma; data cutoff 1 January 2020
• Exposure: The exposure was the experimental ALK inhibitor drug CT-707, taken by mouth at 450 mg once a day (n = 7), 300 mg twice a day (n = 2), or 600 mg once a day (n = 4). Asbestos exposure was not studied.
• Main results:
  • Among all 13 patients, the overall response rate was 10 of 13 (77%) and the disease control rate was 11 of 13 (85%)
  • The one patient with malignant pleural mesothelioma (600 mg group) had disease progression after one cycle and died of tumor progression
  • The dose-escalation section reported one dose-limiting toxicity, grade 3 diarrhea, at 600 mg once daily; the maximum tolerated dose was initially set at 600 mg
  • The patient disposition section states that a different patient, who stopped treatment because of drug-induced liver injury, was also recorded as a dose-limiting toxicity, which conflicts with the single DLT reported elsewhere
  • The most common drug-related adverse events in all patients were diarrhea (92%) and elevated aspartate aminotransferase (61%)
  • Two of 13 patients (15%) had grade 3/4 drug-related adverse events
  • Median progression-free survival in the 13 patients was 13 months (95% CI 9.98 to 16.00)
  • Two patients died of disease progression during the study; neither death was considered related to the drug
• The authors' conclusion: The authors concluded that CT-707 is effective in Chinese patients with tumors harboring ALK rearrangements and has a reliable safety profile and clinical application value
• Limitations the authors state:
  • Only two NSCLC patients with brain metastases who were resistant to crizotinib were included
  • The small number of subjects may explain differences from other trials' response rates

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Non-Small Cell Lung Cancer, Chemotherapy, Fluorescence In Situ Hybridization (FISH), Immunohistochemistry, Lung Adenocarcinoma, Pleural Mesothelioma.

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