Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Futibatinib

Dose escalation: Futibitanib in combination with binimetinib in patients with advanced cancer disease.

Dose expansion: Futibatinib in combination with binimetinib at the RP2D in patients with advanced KRASmt NSCLC

Patients will receive futibatinib once daily in combination with binimetinib twice daily by oral administration on a 21-day cycle

Futibatinib and Binimetinib

Phase 1b/2 study to evaluate the FGFRi futibatinib in combination with the MEKi binimetinib in patients with advanced KRASmt tumors.

This is an open-label, nonrandomized, uncontrolled Phase 1b/2 study to determine the recommended phase 2 dose (RP2D) of futibatinib in combination with binimetinib and to explore the preliminary antitumor activity of futibatinib in combination with binimetinib in patients with advanced KRASmt tumors.

The study will consist of two parts:

* Part 1: Dose-Escalation part to determine the RP2D and dosing schedule of futibatinib in combination with binimetinib in patients with advanced cancer disease
* Part 2: Dose-Expansion part to evaluate the preliminary antitumor activity of futibatinib in combination with binimetinib at the RP2D in patients with advanced KRASmt NSCLC

Patients will receive study treatment until progressive disease or any other discontinuation or withdrawal criterion is met.

Phase 1b/2 Study of Futibatinib in Combination With Binimetinib in Patients With Advanced KRAS Mutant Cancer

A Phase 1b/2 Open-label, Nonrandomized Study of FGFR Inhibitor Futibatinib in Combination With MEK-inhibitor Binimetinib in Patients With Advanced KRAS Mutant Cancer

Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities

proportion of patients who have achieved a PR or complete response (CR) according to RECIST 1.1.

Plasma concentrations of futibatinib, binimetinib, and AR00426032

DOR is defined as the length of time between first response and the date of objectively documented progression of disease or death

PFS is defined as the time from date of first dose to objectively documented progression of disease or death

DCR is defined as the percentage of patients who have achieved a CR, PR, or SD.

Evaluate safety and tolerability of futibatinib in combination with binimetinib based on treatment-emergent adverse events per CTCAE v5.0(including serious adverse events),clinical laboratory parameters, ECGs, and vital signs

Taiho Oncology, Inc.

Advanced or metastatic solid tumors irrespective of gene alterations

Advanced or metastatic solid tumors with germline PTEN inactivating mutations

TAS-117 will be dosed orally every day on a 21-day cycle

TAS-117

TAS-117 will be dosed intermittently on a 21-day cycle

TAS-117 will be dosed orally every day or intermittently on a 21-day cycle

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of TAS-117 in patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations.

Study TAS-117-201 is an open-label, single-arm Phase 2 study evaluating the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of TAS-117 in patients with advanced or metastatic solid tumors harboring germline PTEN inactivating mutations. The study will be conducted in two parts:

* Part A: Safety lead-in (Dose Escalation and Dose Regimen Confirmation)
* Part B: Single-arm Phase 2 study

Patients will receive TAS-117 orally every day or intermittently on a 21-day cycle

* Part A (Dose Escalation): up to 36 adult patients with advanced or metastatic solid tumors (excluding primary brain tumors) irrespective of gene alterations. The Dose Escalation consists of 2 cohorts: Daily Dose Regimen and Intermittent Dose Regimen.
* Part A (Dose Regimen Confirmation): approximately 6 adult or adolescent patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations
* Part B (Phase 2): approximately 54 adult or adolescent patients with advanced or metastatic solid tumors (excluding primary brain tumors) harboring germline PTEN inactivating mutations

Treatment will continue until disease progression, unacceptable toxicity, or any other of the criteria for treatment discontinuation is met. For patients who discontinue treatment for reasons other than disease progression, tumor assessments should be continued until radiologic disease progression is documented or until initiation of subsequent new anticancer therapy (whichever occurs first).

Patients will be followed for survival every 12 weeks (±2 weeks) until survival events (deaths) have been reported for 75% of enrolled patients or the study is terminated early by the Sponsor.

TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations

A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations

Number of patients with abnormal laboratory values, treatment emergent AEs, abnormal vital signs and ECG, and Dose-limiting toxicities (DLTs)

ORR, defined as the proportion of patients experiencing a best overall response of CR or PR per RECIST 1.1.

Number of patients with abnormal laboratory values, treatment-emergent AEs, abnormal vital signs and ECG

DCR, defined as the proportion of patients experiencing a best overall response of stable response (SD), PR, or complete response (CR).

DOR, defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

PFS, defined as the time from date of the first dose of study treatment to the date of disease progression based on Investigator assessment of radiographic images or death, whichever occurs first.

OS, defined as the time from the date of first dose to the death date.

area under the plasma concentration-time curve (AUC)

time to reach maximum plasma concentration (Tmax)

Evaluate Total and Phosphorylated AKT and PRAS40

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase 1b/2 Study of Futibatinib in Combination With Binimetinib in Patients With Advanced KRAS Mutant Cancer	NCT04965818	Advanced or Met... Non-Small Cell ... KRAS Gene Mutat...	Futibatinib and...	18 Years -	Taiho Oncology, Inc.
TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations	NCT04770246	Advanced or Met... Advanced or Met...	TAS-117 TAS-117 TAS-117 TAS-117	12 Years -	Taiho Oncology, Inc.
Phase 1b/2 Study of Futibatinib in Combination With Binimetinib in Patients With Advanced KRAS Mutant Cancer	NCT04965818	Advanced or Met... Non-Small Cell ... KRAS Gene Mutat...	Futibatinib and...	18 Years -	Taiho Oncology, Inc.
TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations	NCT04770246	Advanced or Met... Advanced or Met...	TAS-117 TAS-117 TAS-117 TAS-117	12 Years -	Taiho Oncology, Inc.
TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Mutations	NCT04770246	Advanced or Met... Advanced or Met...	TAS-117 TAS-117 TAS-117 TAS-117	12 Years -	Taiho Oncology, Inc.

Spots Global Cancer Trial Database for advanced or metastatic solid tumors irrespective of gene alterations