Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Fluorouracil

Participants received 400 milligrams (mg) of TAS-114 tablets orally twice daily (BID) along with 30 milligrams per meter square (mg/m\^2) of S-1 capsule BID for 2 weeks (Day 1 to 14), followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 51 weeks).

Participants received 30 mg/m\^2 of S-1 capsules BID for 2 weeks (Day 1 to 14) followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 38 weeks).

TAS-114 was a modulator of 5-fluorouracil (5-FU).

TAS-114

S-1 was designed to provide oral delivery of 5-FU and to reduce the rate of degradation of 5-FU in vivo.

Taiho Central

This is a randomized, open-label, Phase 2 study of TAS-114 administered in combination with S-1, to investigate the efficacy, safety and tolerability of the TAS-114/S-1 regimen in patients with advanced or metastatic NSCLC.

The study will be conducted internationally in 2 regions: Asian \[Japan\] and Western \[Europe and US\]. Patients will be randomized into TAS-114/S-1 arm versus S-1 control arm in a 1:1 ratio.

Randomization will take place once the consented patient has completed all the necessary baseline procedures and is deemed eligible for study entry. Treatment assignment will be done centrally using a dynamic allocation method (biased coin) via an interactive voice/web response system (IXRS) stratified by:

* Geographical region (Region 1: Asian \[Japan\]; Region 2: Western \[Europe and US\])
* Histological subtypes (nonsquamous cell carcinoma \[including mixed\] and squamous cell carcinoma)

A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1

A Randomized, Open-Label, Multi-Center, International Phase 2 Study of TAS-114 in Combination With S-1 in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Progression-free survival was defined as the time (in months) from the day of randomization to the start of radiologic disease progression or death (any cause), whichever occurred first. Response assessments were made based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). As per RECIST 1.1 criteria, progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). (Note: the appearance of one or more new lesions was also considered progressions). Participants who did not have disease progression or died were censored at the last known time that the participant was progression free.

OS was defined as the time from the first dose of the study treatment to death from any cause. Participants who were alive at the end of study were censored at the last date the participant was known to be alive. OS was estimated from Kaplan-Meier method.

ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1. CR was defined as the disappearance of all target lesions and non-target lesions and normalization of tumor marker level. Any pathological and non-pathological lymph nodes must have reduction in short axis to less than (\<) 10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters.

DCR was defined as the percentage of participants with objective evidence CR, PR, or stable disease (SD). Based on the central review of tumor assessments per RECIST, version 1.1. CR was defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameters during study.

DR was derived for participants with objective evidence of PR or CR. DR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. Participants who were alive and progression-free as of the analysis cut-off date were censored at their last evaluable tumor response assessment before initiation of any new anticancer treatment.

An adverse event (AE) was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened during the TEAE period which was defined as the period from the time of first dose of study treatment until 30 days after last dose of study treatment. AEs included both serious and non- serious adverse events.

Taiho Oncology, Inc.

Analysis was performed on As-Treated (AT) population which included all participants who received at least 1 dose of TAS-114 or S-1.

Participants received 400 mg of TAS-114 tablets orally BID along with 30 mg/m\^2 of S-1 capsule BID for 2 weeks (Day 1 to 14), followed by 1 week recovery period (Day 15 to 21) in each 21 days cycle, until progressive disease (PD), occurrence of intolerable side effects, removal by the Investigator, or withdrawal of consent (maximum treatment duration: 51 weeks).

TAS-114 + S-1

S-1 (Monotherapy)

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Baseline population included all participants randomized in the study, regardless of whether they actually received any study treatment (TAS-114 or S-1) or not.

Intent-to-Treat (ITT) population included all participants randomized in the study, regardless of whether they actually received any study treatment (TAS-114 or S-1) or not.

Progression-free Survival (PFS) Based on Central Independent Review

Overall Survival (OS)

Tumor response (TR) population included all participants randomized in the study, regardless of whether they actually received any study treatment (TAS-114 or S-1) or not; with measurable disease (at least one target lesion) at baseline and with at least one tumor evaluation (participants who had disease progression or had a cancer related death prior to their 1st tumor evaluation were also considered evaluable).

Spots Global Cancer Trial Database for A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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