Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 11:53 PM
Ignite Modification Date:
2025-12-24 @ 11:53 PM
NCT ID:
NCT03681951
Brief Summary:
In an unbiased CRISPR screen, RIPK1 was identified as a top gene contributing to immunotherapy resistance. In addition, RIPK1 has been reported to drive pancreatic oncogenesis. In murine models, inhibition of RIPK1 kinase activity in the pancreatic tumor microenvironment leads to the replacement of tumor-permissive myeloid infiltrates with innate cells that promote an effective antitumor response by adaptive cells. The investigators hypothesize that inhibition of RIPK1 in human pancreatic cancer subjects will modulate the immune infiltrate to sensitize tumors to checkpoint blockade.
Detailed Description:
Study 205013 is a Phase 1 FTIH study of GSK3145095 alone and in combination with other anticancer agents including pembrolizumab in subjects with pancreatic ductal adenocarcinoma (PDAC) and other selected tumors. The study includes up to 4 parts: Part 1 dose escalation will be conducted in approximately 30 adult subjects with advanced or metastatic PDAC using escalating doses of GSK3145095 as monotherapy only. Part 2 will combine escalating doses of GSK3145095 with 200 milligram (mg) pembrolizumab. Dose escalation of GSK3145095 will begin at least one level below the highest dose shown to have an acceptable toxicity profile in at least 3 subjects in Part 1. Part 2 may be conducted in a broader population of selected solid tumors using a combination of escalating doses of GSK3145095 and 200 mg pembrolizumab. Part 3 will enroll subjects treated with one or more dose levels of GSK3145095 in combination with 200 mg pembrolizumab. Part 4 will investigate the combination of additional anticancer agents with one or more doses of GSK3145095 identified as safe in Part 1. Up to approximately 220 subjects will be treated in the study. Parts 1 and 2 will each treat up to approximately 30 subjects. Parts 3 and 4 will treat up to approximately 160 subjects (up to 80 subjects in each Part). The total duration of the study is expected to last up to 2 years.
Study:
NCT03681951
Study Brief:
Protocol Section:
NCT03681951