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

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

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

Study Overview

• Status: Terminated
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: TAS0612

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Bouches Du Rhone
    • Marseille, Bouches Du Rhone, France, 13009
      • Institut Paoli Calmette
  • Val De Marne
    • Villejuif, Val De Marne, France, 94805
      • Centre de Lutte Contre le Cancer Gustave Roussy
• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Dose Escalation:

Have histologically confirmed, locally advanced, and unresectable cancer, or metastatic cancer and have progressed on or were intolerant to standard treatments or refused standard of care (SOC).

Dose Expansion:

Have documented histologically or cytologically confirmed adenocarcinoma of the prostate with documented PTEN loss or loss of function mutation, who have metastatic castration-resistant disease and have:

• Disease progression per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3)/modified RECIST 1.1 after the most recent regimen.
• Received androgen receptor directed therapy previously with or without chemotherapy consisting of no more than 2 prior taxane-based regimens.
• Been receiving androgen deprivation therapy with serum testosterone <50 ng/dL (<2.0 nM). Note: previously documented PTEN loss or loss of function mutation from archived tissue sample testing or cfDNA sample testing is acceptable if done in a CLIA certified lab or a locally certified lab.

Have an ECOG score of 0 or 1 Dose Escalation (Part 1): Have no measurable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Dose Expansion (Part 2): Have measurable or no measurable disease per PCWG3/modified RECIST 1.1

• No more than 30 patients with no measurable disease will be enrolled in Dose Expansion (Part 2).

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAS0612 Escalation; TAS0612 administered orally	Drug: TAS0612; oral tablets
Experimental: TAS0612 Expansion; TAS0612 administered orally	Drug: TAS0612; oral tablets

What is the study measuring?

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)
rPFS rate	Percentage of participants with partial response (PR) or complete response (CR) at 6 months Prostate Cancer Working Group 3 (PCWG3)/ modified defined by the Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1.	Baseline through measured progressive disease (estimated up to 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR) per PCWG3/mRECIST1.1	DCR: Percentage of participants who exhibit stable disease (SD), PR or CR.	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
Duration of Response (DOR) per PCWG3/mRECIST1.1	DOR: Date of PR or CR to date of objective progression or death due to any cause.	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
Radiographic Progression Free Survival (rPFS) per PCWG3/mRECIST1.1	Proportion of patients experiencing a radiographic progression by PCWG3/mRECIST1.1 criteria	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 6 months.
Overall Response Rate (ORR) per PCWG3/mRECIST1.1	Proportion of patients experiencing a best overall response of Complete Response (CR) or Partial response (PR)	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
Prostatic Specific Antigen (PSA) Response	Proportion of patients with ≥50% reduction in PSA from baseline to lowest post-baseline result.	Baseline to PSA progression, up to 12 months
Pharmacokinetics (PK) parameters including but not limited to: Cmax	time of TAS0612 it takes to reach Cmax.	Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
Pharmacokinetics (PK) parameters including but not limited to: Tmax	time of TAS0612 it takes to reach Cmax,	Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
Pharmacokinetics (PK) parameters including but not limited to: AUC.	Area under the plasma concentration curve of TAS0612.	Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
Pharmacokinetics (PK) parameters including but not limited to: T1/2.	time it takes for plasma concentration to fall by half its original value (t1/2) of TAS0612	Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle) Cycle 2 Day 1 and Cycle 3 Day 1
Safety and Tolerability	All adverse events (AEs) per CTCAE v5.0.	From screening to 30 days after last dose
Pharmacodynamic: biochemical effects of TAS0612: Total proteins	Total proteins will be measured in blood samples collected at different time points.	Cycle 1 Day 1 through Cycle 1 Day 15 (28-day cycle)
Pharmacodynamic: biochemical effects of TAS0612: phospho-proteins	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) through study completion, an average of 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Metabolites in plasma	Structure elucidation of TAS0612 metabolites in human plasma.	Cycle 1 Day 1 (each cycle is 28 days).
Time-matched plasma exposures of TAS0612 and changes from baseline in QTcF using central ECG measurements	To explore the correlation between the incidence of exposures of TAS0612 in plasma and QT prolongation	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months
Exploratory correlation of tissue and/or blood markers with tumor efficacy endpoints and/or tumor resistance to TAS0612	To investigate potential predictive biomarkers for TAS0612.	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.
Exposure of TAS0612 and selected efficacy and safety measures.	To explore the correlation between PK and antitumor activity or toxicity	Baseline through progressive disease or date of death for any causes, whichever comes first, assessed up to 12 months.

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): November 14, 2024
• Study Completion (Actual): November 14, 2024

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 11, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Prostate cancer; phase I; Solid Tumors; kinase inhibitor; PTEN loss; AKT inhibitor; RSK inhibitor; S6K inhibitor; PTEN mutation
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TAS0612-101; 2020-002304-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No