TAS0612 for Advanced or Metastatic Cancer

Recruiting at 3 trial locations

Overseen By Taiho Oncology, INC

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Taiho Oncology, Inc.

Must be taking: Androgen deprivation therapy

Must not be taking: CYP3A inhibitors/inducers

Disqualifiers: Cardiac condition, Brain metastases, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

47 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called TAS0612 to see if it is safe for people with advanced or metastatic solid tumor cancer.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those taking strong inhibitors or inducers of CYP3A (a liver enzyme that affects drug metabolism). It's best to discuss your current medications with the trial team.

What is known about the safety of TAS0612 (also known as TAS-115) in humans?

TAS-115, a similar treatment to TAS0612, has been generally well tolerated in clinical trials for various cancers, with some manageable side effects like decreased blood cell counts and skin rash. The most common serious side effects included low white blood cell counts, low phosphate levels, and low platelet counts, but these were considered manageable. ^{1 2 3 4 5}

What makes the drug TAS0612 unique for treating advanced or metastatic cancer?

TAS0612 is unique because it is an oral multi-kinase inhibitor, similar to TAS-115, which targets specific proteins involved in cancer growth and spread, potentially offering a new option for patients with limited treatment choices. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for adults with advanced or metastatic solid tumors, excluding brain tumors. Participants must have good organ function and a performance status of 0 or 1 on the ECOG scale. Specific cohorts include those with certain genetic mutations like PTEN loss, KRAS G12D/C mutation, NF1 mutation in HER2 negative breast cancer, and HR+/HER2 negative breast cancer resistant to standard treatments.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My organs are functioning well.

My cancer is advanced or has spread but does not originate from the brain.

Exclusion Criteria

I cannot swallow or digest pills.

I have a brain tumor that originated in my brain.

My diabetes is not well-managed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of TAS0612 to determine the maximum tolerated dose

28 days

Cycle 1 Day 1 through Cycle 1 Day 15

Dose Expansion

Participants receive TAS0612 at the determined dose to further evaluate safety and efficacy

28 days

Cycle 2 Day 1 and Cycle 3 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• TAS0612

Trial Overview The study is testing TAS0612's safety for patients with various types of advanced solid tumors. It includes different phases: dose escalation to find the safe dosage levels and dose expansion to test effectiveness in specific patient groups defined by genetic characteristics of their cancers.

Participant Groups

Group I: TAS0612 Expansion Experimental Treatment 1 Intervention

TAS0612 administered orally

Group II: TAS0612 Escalation Experimental Treatment 1 Intervention

TAS0612 administered orally

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Findings from Research

Targeted therapies using BRAF and MEK inhibitors have become the standard treatment for advanced-stage BRAF V600-mutant melanoma, significantly improving patient outcomes.

Effective management of drug-related adverse events (AEs) is crucial for maximizing treatment benefits, as understanding the specific toxicity profiles of these inhibitors allows for timely adjustments in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. Daud, A., Tsai, K.[2019]

Dabrafenib plus trametinib has been approved for treating non-small cell lung cancer (NSCLC) with the BRAF V600E mutation, showing a response rate of approximately 65% and a median progression-free survival of 10-11 months based on clinical trials.

While the combination therapy has a manageable safety profile, it presents unique toxicities such as pyrexia, fatigue, and nausea, which may be unfamiliar to oncologists treating lung cancer, but can be effectively managed using strategies developed from experience in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib. Chalmers, A., Cannon, L., Akerley, W.[2020]

In a study of 43 patients with metastatic colorectal cancer (mCRC) who were resistant to standard treatments, TAS-102 provided clinically relevant disease control in 30% of patients, particularly those treated for 6 or more cycles, with a median progression-free survival of 7.5 months and overall survival of 11.2 months.

A significant correlation was found between previous treatment success with regorafenib and the efficacy of TAS-102, suggesting that patients who responded well to regorafenib may benefit more from subsequent treatment with TAS-102.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme. Sforza, V., Martinelli, E., Cardone, C., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase I study of TAS-115, a novel oral multi-kinase inhibitor, in patients with advanced solid tumors. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A Phase II, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With Bone Metastases. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Adverse Event Management in Patients with BRAF V600E-Mutant Non-Small Cell Lung Cancer Treated with Dabrafenib plus Trametinib. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

A Phase I Clinical Trial of Trametinib in Combination with TAS-102 in Patients with Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild Type) Metastatic Colorectal Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme. [2021]