A phase 1b study of the allosteric extracellular FGFR2 inhibitor alofanib in patients with pretreated advanced gastric cancer

by Selleckchem | Oct 14 2023

Alofanib is a small-molecule allosteric extracellular FGFR2 inhibitor. We report safety and preliminary efficacy from the first-in-human phase 1b study of alofanib in heavily pretreated patients with advanced gastric cancer. The standard dose-escalation design 3+3 aimed to establish the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Alofanib was administered daily intravenously 5 days on, 2 days off. There were five dose levels (50-350 mg/m2). All patients received alofanib until disease progression or unacceptable toxicity. 21 patients were enrolled. Patients were predominantly male (71%), 67% had 2 and more metastatic sites, including liver metastases (43%), 19% had ECOG PS 2, and were heavily pretreated (86% had previous 2 and more treatment lines). During dose escalation, no dose-limiting toxicities were observed, and MTD was not defined. 15 (71.4%) patients had at least one adverse event associated with the treatment (TRAE). Grade 3 or higher TRAEs were observed in 6 patients (28.6%). The most common TRAEs included reactions immediately after administration, diarrhea, thrombocytopenia, arthralgia, and headache. The median progression-free survival and overall survival was 3.63 (95% CI 1.58-5.68) and 7.0 (95% CI 3.82-10.18) months, respectively. The 6- and 12-month overall survival rates were 57.1% and 33.3%. Disease control rate was 68% with one durable partial response. The MTD has not been reached and dose of 350 mg/m2, 5 days on, 2 days off has been declared as RP2D. Alofanib showed acceptable tolerability and preliminary signs of clinical activity in the late-line treatment of metastatic gastric cancer.

Comments:

Thank you for providing the information on alofanib and the phase 1b study conducted in patients with advanced gastric cancer. Here's a summary of the key findings:

- Alofanib is a small-molecule allosteric extracellular FGFR2 inhibitor.
- The phase 1b study aimed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of alofanib.
- The study used a standard dose-escalation design (3+3) and included five dose levels ranging from 50-350 mg/m2.
- Alofanib was administered intravenously on a daily basis for 5 days, followed by 2 days off.
- A total of 21 heavily pretreated patients with advanced gastric cancer were enrolled in the study.
- The majority of patients were male (71%), had multiple metastatic sites (67%), including liver metastases (43%), and 19% had an Eastern Cooperative Oncology Group performance status of 2 (ECOG PS 2).
- Most patients (86%) had received at least two prior lines of treatment.
- During dose escalation, no dose-limiting toxicities were observed, and the MTD was not defined.
- Adverse events associated with the treatment (TRAEs) were reported in 71.4% of patients, with grade 3 or higher TRAEs observed in 28.6% of patients.
- Common TRAEs included immediate reactions after administration, diarrhea, thrombocytopenia, arthralgia, and headache.
- The median progression-free survival was 3.63 months (95% CI 1.58-5.68), and the overall survival was 7.0 months (95% CI 3.82-10.18).
- The 6- and 12-month overall survival rates were 57.1% and 33.3%, respectively.
- The disease control rate was 68%, and there was one durable partial response.
- The MTD was not reached in the study, and the dose of 350 mg/m2, administered 5 days on and 2 days off, was declared as the recommended phase 2 dose (RP2D).
- Alofanib demonstrated acceptable tolerability and showed preliminary signs of clinical activity in the late-line treatment of metastatic gastric cancer.

Please note that the information provided is based on the summary you provided and may not include all the details from the original study.