A Study of TAS0612 in Participants With Advanced or Metastatic Solid Tumor Cancer

Study Overview
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Brief Summary
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The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.

Official Title
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A Phase 1 Study of TAS0612 in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: TAS0612


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dose Escalation: have evidence of a solid tumor that is locally advanced and/or metastatic (excluding primary brain tumor) Dose Expansion: have evidence of a solid tumor as outlined below that is locally advanced and/or metastatic (excluding primary brain tumor) Cohort A: Human epidermal growth factor negative (HER2 negative) Breast Cancer with an NF1 mutation Cohort B: Hormone receptor positive (HR+)/HER2 negative breast cancer after progression on endocrine therapy and a CDK4/6 inhibitor Cohort C: PTEN loss or mutations Cohort D: KRAS G12C mutation Cohort E: KRAS G12D mutation Have adequate organ function Amenable to biopsy Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale Exclusion Criteria: Participating in medical research not compatible with this study Have not discontinued or recovered from previous treatments for cancer Have a significant cardiac condition Have untreated brain metastases Have a primary brain tumor Have a serious concomitant disorder Unable to swallow or digest pills Poorly controlled diabetes Concomitant medications or substances that are strong inhibitors/inducers of CYP3A.Study

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS0612 Escalation<br>TAS0612 administered orally | Drug: TAS0612<br>* oral tablets<br>|
| Experimental: TAS0612 Expansion<br>TAS0612 administered orally | Drug: TAS0612<br>* oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLTs) | Number of participants with DLTs during cycle 1 | Baseline through Cycle 1 (28 day cycle) | 
| Objective Response Rate | Percentage of participants with partial response (PR) or complete response (CR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Baseline through measured progressive disease (estimated up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | DCR: Percentage of participants who exhibit stable disease (SD), PR or CR. | Baseline through progressive disease (estimated up to 24 months) | 
| Duration of Response (DOR) | DOR: Date of PR or CR to date of objective progression or death due to any cause. | Estimated up to 22 months | 
| Progression Free Survival (PFS) | Baseline to objective progression or death due to any cause. | Estimated up to 24 months | 
| Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of TAS0612 | Cmax of TAS0612 | Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle) | 
| Pharmacokinetics (PK): plasma concentration of TAS0612 | Plasma concentration of TAS0612 | Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle) | 
| PK: Area under the plasma concentration curve (AUC) | AUC of TAS0612 | Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle) | 
| PK: Time it takes to reach Cmax (Tmax) of TAS0612 | Tmax of TAS0612 | Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle) | 
| PK: Time it takes for plasma concentration to fall by half its original value (t1/2) of TAS0612 | t1/2 of TAS0612 | Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle) | 
| Safety and Tolerability | All adverse events (AEs) per CTCAE v5.0 | Estimated up to 24 months | 
| Pharmacodynamic: biochemical effects of TAS0612 | Total proteins and phospho-proteins will be measured in blood samples collected at different time points. The levels/changes (dose- and concentration-dependent) of phospho-proteins will be assessed and reported for biochemical effects of TAS0612. | Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) | 
| Pharmacodynamic: molecular effects in tumor tissue of TAS0612 | Selected phospho-proteins will be analyzed in tumor tissue at baseline and on-treatment in dose escalation. The levels/changes of the phospho-proteins will be assessed and reported for target modulation. | Baseline through Day 1 Cycle 2 (28-day cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, AKT inhibitor, RSK inhibitor, S6K inhibitor, kinase inhibitor, phase I, phase 1, NF1 mutation, endocrine therapy resistance, PTEN loss, PTEN mutation, KRAS G12C, KRAS G12D, breast cancer