Study to Assess GTAEXS617 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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A phase 1/2 study to assess the safety, tolerability, pharmacokinetics and anti-tumor activity of GTAEXS617-001 in patients with advanced solid tumors.

Detailed Description
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A phase 1/2 study to assess the safety, tolerability, pharmacokinetics and anti-tumor activity of GTAEXS617-001 as monotherapy and in combination, in patients with one of the following advanced solid tumors: head and neck squamous cell carcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma, non-small cell lung cancer, breast cancer (HR+ and HER2- that has progressed to a prior treatment with CD4/CDK6 inhibitor), ovarian epithelial carcinoma.

Official Title
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A Phase 1/2 Open-label Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti-tumor Activity of GTAEXS617 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: GTAEXS617


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ECOG performance status 0-1 Life expectancy >3 months One the following histologically or cytologically confirmed advanced solid tumors: head and neck squamous cell carcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma, NSCLC, breast carcinoma (HR+ and HER2- that has progressed to a prior treatment with CD4/CDK6 inhibitor), or ovarian epithelial carcinoma Patients must have disease that is advanced (ie, surgery or radiotherapy are not considered to be potentially curative), recurrent, or metastatic following SoC treatments Adequate hematological, liver, and renal function Participant must have tumor lesion(s) or metastases amenable to biopsy, excluding bone metastases Exclusion Criteria: Active and clinically significant (CS) infection Refractory nausea and/or vomiting, chronic gastrointestinal disease, or previous significant bowel resection, with CS sequelae that would preclude adequate absorption of GTAEXS617 Symptomatic central nervous system (CNS) malignancy or metastases Concurrent active or previous malignancy Prior organ or allogeneic stem-cell transplantation Moderate or severe cardiovascular disease Received anticancer therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of the study treatment Received treatment with known strong inhibitors and or inducers of cytochrome P450 3A isoform subfamily (CYP3A) within 14 days or 5 half-lives before the first dose of study treatment Received treatment with known inhibitors or inducers of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) within 14 days or 5 half-lives before the first dose of study Received treatment with known substrates of organic anion transporting peptide 1B3 (OATP1B3) or BCRP within 14 days or 5 half-lives before the first dose of study treatment Unresolved or unstable serious toxic side-effects of prior chemotherapy or radiotherapy Has had or is scheduled to have major surgery <28 days prior to the first dose of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GTAEXS617<br>GTAEXS617 tablet for oral administration | Drug: GTAEXS617<br>* GTAEXS617 tablets daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Module 1 Part A: To characterize the safety profile of GTAEXS617 as monotherapy | Incidence of treatment-emergent adverse events (TEAEs), characterised by type, incidence, severity (graded by NCI CTCAE v5.0), seriousness, timing and relationship to GTAEXS617 dosing. | Through patient study completion, an average of 6 months | 
| Module 1 Part A: To characterize the Dose Limiting Toxicities (DLTs) of GTAEXS617 as monotherapy | Incidence of dose limiting toxicities (DLTs) during Cycle 1 of treatment. | Through patient study completion, an average of 6 months | 
| Module 1 Part A: To establish the Recommended Phase 2 Dose (RP2D) of GTAEXS617 as monotherapy | The RP2D will not exceed the maximum tolerated dose (MTD) if established. | Through study completion for all patients in Module 1 Part A. Estimated 18 months. | 
| Module 1 Part B: To characterize the safety profile of GTAEXS617 in combination with selected Standard of Care (SoC) regimens | Incidence of treatment-emergent adverse events (TEAEs), characterised by type, incidence, severity (graded by NCI CTCAE v5.0), seriousness, timing and relationship to GTAEXS617 dosing. | Through patient study completion, an average of 6 months | 
| Module 1 Part B: To characterize the Dose Limiting Toxicities (DLTs) of GTAEXS617 in combination with selected Standard of Care (SoC) regimens | Incidence of dose limiting toxicities (DLTs) during Cycle 1 of treatment | Through patient study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Module 1 Part A: GTAEXS617 Maximum Plasma Concentration (Cmax) | Maximum Plasma Concentration (Cmax) when GTAEXS617 administered as monotherapy | Through patient study completion, an average of 6 months | 
| Module 1 Part A: GTAEXS617 Time Maximum Plasma Concentration (Tmax) | Time Maximum Plasma Concentration (Tmax) when GTAEXS617 administered as monotherapy | Through patient study completion, an average of 6 months | 
| Module 1 Part A: GTAEXS617 Area under Plasma Concentration Curve during 24 hour dosing interval (AUC 0-tau) | Area under Plasma Concentration Curve during 24 hour dosing interval (AUC 0-tau) when GTAEXS617 administered as monotherapy | Through patient study completion, an average of 6 months |