BridgeMD
FTIH study to investigate the safety and preliminary efficacy of the DNA-repair inhibitor GSK4418959 alone or in combination with other anti-cancer agents in dMMR/MSI-H solid tumors
EU CTIS ID: 2024-519721-37-00
What this study is testing
"Part 1: Determine the maximum tolerated dose and/or recommended dose for expansion for GSK4418959 as monotherapy; assess safety and tolerability of GSK4418959 as monotherapy within the dose-limiting toxicity (DLT) observation period Part 2: Evaluate the preliminary anti-tumor activity of GSK4418959 in colorectal cancer and, separately, in endometrial cancer Part 3: Determine the maximum tolerated dose and/or recommended dose for expansion for GSK4418959 in combination with a PD-1 inhibitor; assess safety and tolerability of GSK4418959 in combination with a PD-1 inhibitor within the DLT observation period"
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- "Participant is at least 18 years of age. "
- Part 2: Participant has measurable disease (i.e., at least 1 target lesion) during the Screening period per RECIST 1.1, as determined by the investigator.
- Participant has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor.
- Participant has a tumor demonstrating either: -Mismatch repair deficient (dMMR) status as assessed by immunohistochemistry (IHC) for expression of the MMR proteins (MLH1, MSH2, MSH6, PMS2) and where loss of 1 or more of these proteins indicates dMMR; OR -Microsatellite instability-high (MSI-H) phenotype as determined by PCR or by tissue NGS.
- Participant has an ECOG performance status of 0-2, with no deterioration in the 2 weeks before Cycle 1 Day 1.
- Participant is expected to have a minimum of 3 months life expectancy.
You likely can't join if
- "Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced AEs. "
- Participant has an active autoimmune disease that has required systemic treatment in the past 2 years.
- "Part 3: Participant has experienced any of the following with prior immunotherapy: any imAE of Grade ≥3, immune-mediated severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary. "
- Part 3: Participant has any history of interstitial lung disease or pneumonitis.
- Participant has received prior treatment with a WRN inhibitor.
- Participant is unable to swallow and retain orally administered study treatment.
See the full eligibility criteria
- "Participant is at least 18 years of age. "
- Part 2: Participant has measurable disease (i.e., at least 1 target lesion) during the Screening period per RECIST 1.1, as determined by the investigator.
- Participant has a histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor.
- Participant has a tumor demonstrating either: -Mismatch repair deficient (dMMR) status as assessed by immunohistochemistry (IHC) for expression of the MMR proteins (MLH1, MSH2, MSH6, PMS2) and where loss of 1 or more of these proteins indicates dMMR; OR -Microsatellite instability-high (MSI-H) phenotype as determined by PCR or by tissue NGS.
- Participant has an ECOG performance status of 0-2, with no deterioration in the 2 weeks before Cycle 1 Day 1.
- Participant is expected to have a minimum of 3 months life expectancy.
- For participants with biopsiable disease and when medically feasible: must provide a fresh biopsy at Screening and must be willing to undergo another on-treatment biopsy.
- Parts 1 and 3: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) solid tumor and has exhausted all standard of care treatment options.
- Part 2: Participant has histologically diagnosed advanced (unresectable, metastatic or recurrent) CRC or EC.
- Part 2: Participant has received at least 1 but no more than 3 lines of systemic anticancer therapy for their advanced (unresectable, metastatic or recurrent) disease (i.e., participants are being treated on study in a 2nd to 4th line metastatic setting), including at least one line of ICI therapy.
- "Participant has not recovered (i.e., to Grade ≤1 or to baseline) from prior anticancer therapy-induced AEs. "
- Participant has an active autoimmune disease that has required systemic treatment in the past 2 years.
- "Part 3: Participant has experienced any of the following with prior immunotherapy: any imAE of Grade ≥3, immune-mediated severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary. "
- Part 3: Participant has any history of interstitial lung disease or pneumonitis.
- Participant has received prior treatment with a WRN inhibitor.
- Participant is unable to swallow and retain orally administered study treatment.
- Participant has symptomatic uncontrolled brain or leptomeningeal metastases.
- Has any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of study drugs (e.g., severe ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection), except for prior gastrectomy.
- Participant has severe liver fibrosis.
- Participant has cirrhosis or current unstable liver or biliary disease.
- Participant has known hypersensitivity to any of the study interventions or any of their excipients.
- Participant has known WRN syndrome.
The study team makes the final eligibility decision.
Where it's taking place
- Korea, Republic of
- Australia
- United States
- Japan
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Korea, Republic of; Australia; United States; Japan. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.