The purpose of this study is to see if TAS0612 is safe in participants with advanced or metastatic solid tumor cancer.
Name: TAS0612
Description: Number of participants with DLTs during cycle 1
Measure: Dose Limiting Toxicities (DLTs) Time: Baseline through Cycle 1 (28 day cycle)Description: Percentage of participants with partial response (PR) or complete response (CR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measure: Objective Response Rate Time: Baseline through measured progressive disease (estimated up to 24 months)Description: DCR: Percentage of participants who exhibit stable disease (SD), PR or CR.
Measure: Disease Control Rate (DCR) Time: Baseline through progressive disease (estimated up to 24 months)Description: DOR: Date of PR or CR to date of objective progression or death due to any cause.
Measure: Duration of Response (DOR) Time: Estimated up to 22 monthsDescription: Baseline to objective progression or death due to any cause.
Measure: Progression Free Survival (PFS) Time: Estimated up to 24 monthsDescription: Cmax of TAS0612
Measure: Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of TAS0612 Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)Description: Plasma concentration of TAS0612
Measure: Pharmacokinetics (PK): plasma concentration of TAS0612 Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)Description: AUC of TAS0612
Measure: PK: Area under the plasma concentration curve (AUC) Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)Description: Tmax of TAS0612
Measure: PK: Time it takes to reach Cmax (Tmax) of TAS0612 Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)Description: t1/2 of TAS0612
Measure: PK: Time it takes for plasma concentration to fall by half its original value (t1/2) of TAS0612 Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28 day cycle)Description: All adverse events (AEs) per CTCAE v5.0
Measure: Safety and Tolerability Time: Estimated up to 24 monthsDescription: 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.
Measure: Pharmacodynamic: biochemical effects of TAS0612 Time: Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle)Description: 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.
Measure: Pharmacodynamic: molecular effects in tumor tissue of TAS0612 Time: Baseline through Day 1 Cycle 2 (28-day cycle)Allocation: Non-Randomized
Single Group Assignment
There are 2 SNPs
The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. 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 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 Advanced or Metastatic Solid Tumors Neoplasms null --- G12C ---
The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. 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 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 Advanced or Metastatic Solid Tumors Neoplasms null --- G12C --- --- G12D --- --- G12C ---
The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. 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 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 Advanced or Metastatic Solid Tumors Neoplasms null --- G12C --- --- G12D ---
The levels/changes of the phospho-proteins will be assessed and reported for target modulation.. 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 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 Advanced or Metastatic Solid Tumors Neoplasms null --- G12C --- --- G12D --- --- G12C --- --- G12D ---