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

• ClinicalTrials.gov Identifier: NCT02855125
• Recruitment Status: Completed
• First Posted: August 4, 2016
• Results First Posted: December 23, 2021
• Last Update Posted: December 23, 2021
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced or Metastatic Non-small Cell Lung Cancer
• Interventions: Drug: TAS-114; Drug: S-1
• Enrollment: 128

Participant Flow

Recruitment Details	The study was conducted at 26 centers in 5 countries.
Pre-assignment Details	A total of 128 participants were randomized.1 participant in S-1 (Monotherapy) arm was randomized but not treated.

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description	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).
Period Title: Overall Study
Started	64	64
Treated	64	63
Completed	0	0
Not Completed	64	64
Reason Not Completed
Withdrawal by Subject	2	2
Clinical Disease Progression	5	4
Radiologic Disease Progression	36	39
Adverse Event	11	7
Physician Decision	1	0
On Treatment	9	11
Randomized but not treated	0	1

Baseline Characteristics

Arm/Group Title		TAS-114 + S-1	S-1 (Monotherapy)	Total
Arm/Group Description		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).	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).	Total of all reporting groups
Overall Number of Baseline Participants		64	64	128
Baseline Analysis Population Description		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.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	64 participants	64 participants	128 participants
		63.8 (7.77)	62.6 (10.22)	63.2 (9.06)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	64 participants	128 participants
	Female	23 35.9%	16 25.0%	39 30.5%
	Male	41 64.1%	48 75.0%	89 69.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	64 participants	128 participants
	Hispanic or Latino	8 12.5%	5 7.8%	13 10.2%
	Not Hispanic or Latino	45 70.3%	47 73.4%	92 71.9%
	Unknown or Not Reported	11 17.2%	12 18.8%	23 18.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	64 participants	64 participants	128 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	30 46.9%	30 46.9%	60 46.9%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	21 32.8%	21 32.8%	42 32.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	13 20.3%	13 20.3%	26 20.3%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) Based on Central Independent Review
Description	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.
Time Frame	From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	64	64
Median (95% Confidence Interval); Unit of Measure: months
	3.65; (2.69 to 5.16)	4.17; (2.60 to 6.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-114 + S-1, S-1 (Monotherapy)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2744
	Comments	[Not Specified]
	Method	Log Rank
	Comments	1-sided stratified log-rank test.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.88
	Estimation Comments	Based on stratified Cox regression model .

2. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	From date of randomization until death (approximately up to 15 months)

Outcome Measure Data

Analysis Population Description

ITT population.

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	64	64
Median (95% Confidence Interval); Unit of Measure: months
	7.92; (6.28 to 10.78)	9.82; (7.66 to 13.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAS-114 + S-1, S-1 (Monotherapy)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1431
	Comments	[Not Specified]
	Method	Log Rank
	Comments	1-sided stratified log-rank test.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.80 to 2.14
	Estimation Comments	Based on stratified Cox regression model.

3. Secondary Outcome

Title	Overall Response Rate (ORR) Based on Central Independent Review
Description	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.
Time Frame	From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	61	58
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	19.7; (10.6 to 31.8)	10.3; (3.9 to 21.2)

4. Secondary Outcome

Title	Disease Control Rate (DCR) Based on Central Independent Review
Description	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.
Time Frame	From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)

Outcome Measure Data

Analysis Population Description

TR population.

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	61	58
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	80.3; (68.2 to 89.4)	75.9; (62.8 to 86.1)

5. Secondary Outcome

Title	Duration of Response (DR) Based on Central Independent Review
Description	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.
Time Frame	From date of first response to the date of first documentation of progression or death (approximately up to 13 months)

Outcome Measure Data

Analysis Population Description

TR population.

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	12	6
Median (95% Confidence Interval); Unit of Measure: months
	3.38; (2.37 to 4.86)	NA [1]; (2.79 to NA)

[1]

Median and upper limit of 95% Confidence interval were not estimable because of censoring in 5 of the 6 participants.

6. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description	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.
Time Frame	From first dose of study drug up to 30 days after the last dose of study drug (approximately up to 13 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	TAS-114 + S-1	S-1 (Monotherapy)
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	64	63
Measure Type: Count of Participants; Unit of Measure: Participants
Participants with TEAEs	64 100.0%	61 96.8%
Participants with TESAEs	30 46.9%	19 30.2%

Adverse Events

Time Frame	From first dose of study drug up to 30 days after the last dose of study drug (approximately up to 13 months)
Adverse Event Reporting Description	Analysis was performed on As-Treated (AT) population which included all participants who received at least 1 dose of TAS-114 or S-1.
Arm/Group Title	TAS-114 + S-1		S-1 (Monotherapy)
Arm/Group Description	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).		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).
All-Cause Mortality
	TAS-114 + S-1		S-1 (Monotherapy)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	36/64 (56.25%)		29/63 (46.03%)
Serious Adverse Events
	TAS-114 + S-1		S-1 (Monotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/64 (46.88%)		19/63 (30.16%)
Blood and lymphatic system disorders
Anaemia † 1	2/64 (3.13%)	2	0/63 (0.00%)	0
Thrombocytopenia † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Cardio-respiratory arrest † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Endocrine disorders
Hypopituitarism † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Pituitary-dependent Cushing's syndrome † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	1/64 (1.56%)	2	0/63 (0.00%)	0
Ascites † 1	1/64 (1.56%)	2	0/63 (0.00%)	0
Diarrhoea † 1	2/64 (3.13%)	2	1/63 (1.59%)	1
Enteritis † 1	1/64 (1.56%)	2	0/63 (0.00%)	0
Mechanical ileus † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Vomiting † 1	0/64 (0.00%)	0	1/63 (1.59%)	3
General disorders
Disease progression † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
General physical health deterioration † 1	1/64 (1.56%)	1	1/63 (1.59%)	1
Multiple organ dysfunction syndrome † 1	1/64 (1.56%)	2	0/63 (0.00%)	0
Pyrexia † 1	1/64 (1.56%)	1	1/63 (1.59%)	1
Hepatobiliary disorders
Cholelithiasis † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Infections and infestations
Bronchitis † 1	3/64 (4.69%)	4	0/63 (0.00%)	0
Lower respiratory tract infection † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Lung infection † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Pneumonia † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Pneumonia influenzal † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Sepsis † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Septic shock † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Staphylococcal sepsis † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Urinary tract infection † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Injury, poisoning and procedural complications
Femoral neck fracture † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/64 (1.56%)	2	0/63 (0.00%)	0
Dehydration † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Hyperkalaemia † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Hyponatraemia † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Metabolic alkalosis † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Metastases to central nervous system † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Metastases to meninges † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Squamous cell carcinoma of skin † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Tumour pain † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Nervous system disorders
Cognitive disorder † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Encephalopathy † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Paraesthesia † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Acute respiratory failure † 1	2/64 (3.13%)	2	0/63 (0.00%)	0
Chronic obstructive pulmonary disease † 1	1/64 (1.56%)	2	1/63 (1.59%)	1
Dyspnoea † 1	4/64 (6.25%)	5	1/63 (1.59%)	1
Hypoxia † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Lung disorder † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Pleural effusion † 1	0/64 (0.00%)	0	2/63 (3.17%)	2
Pneumonia aspiration † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
Pneumothorax † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Pulmonary embolism † 1	4/64 (6.25%)	4	1/63 (1.59%)	1
Pulmonary haemorrhage † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Respiratory acidosis † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Respiratory failure † 1	2/64 (3.13%)	2	0/63 (0.00%)	0
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Purpura † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Rash † 1	2/64 (3.13%)	3	0/63 (0.00%)	0
Rash maculo-papular † 1	3/64 (4.69%)	3	0/63 (0.00%)	0
Stevens-Johnson syndrome † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Vascular disorders
Hypotension † 1	1/64 (1.56%)	1	0/63 (0.00%)	0
Vena cava thrombosis † 1	0/64 (0.00%)	0	1/63 (1.59%)	1
1 Term from vocabulary, MedDRA 19.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	TAS-114 + S-1		S-1 (Monotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/64 (100.00%)		61/63 (96.83%)
Blood and lymphatic system disorders
Anaemia † 1	42/64 (65.63%)	111	17/63 (26.98%)	26
Neutropenia † 1	5/64 (7.81%)	14	1/63 (1.59%)	1
Thrombocytopenia † 1	4/64 (6.25%)	5	2/63 (3.17%)	5
Eye disorders
Lacrimation increased † 1	5/64 (7.81%)	5	5/63 (7.94%)	5
Gastrointestinal disorders
Abdominal pain † 1	3/64 (4.69%)	4	5/63 (7.94%)	5
Abdominal pain upper † 1	4/64 (6.25%)	5	3/63 (4.76%)	6
Constipation † 1	9/64 (14.06%)	9	9/63 (14.29%)	10
Diarrhoea † 1	19/64 (29.69%)	32	18/63 (28.57%)	24
Nausea † 1	20/64 (31.25%)	61	23/63 (36.51%)	62
Stomatitis † 1	10/64 (15.63%)	18	4/63 (6.35%)	5
Vomiting † 1	12/64 (18.75%)	32	13/63 (20.63%)	18
General disorders
Asthenia † 1	19/64 (29.69%)	40	14/63 (22.22%)	22
Fatigue † 1	6/64 (9.38%)	12	11/63 (17.46%)	18
Malaise † 1	10/64 (15.63%)	18	5/63 (7.94%)	6
Mucosal inflammation † 1	4/64 (6.25%)	5	3/63 (4.76%)	3
Non-cardiac chest pain † 1	6/64 (9.38%)	7	3/63 (4.76%)	4
Oedema peripheral † 1	5/64 (7.81%)	6	4/63 (6.35%)	7
Pyrexia † 1	14/64 (21.88%)	17	9/63 (14.29%)	12
Infections and infestations
Bronchitis † 1	1/64 (1.56%)	1	5/63 (7.94%)	5
Investigations
Alanine aminotransferase increased † 1	3/64 (4.69%)	7	4/63 (6.35%)	7
Aspartate aminotransferase increased † 1	4/64 (6.25%)	6	6/63 (9.52%)	9
Blood bilirubin increased † 1	0/64 (0.00%)	0	5/63 (7.94%)	12
Lymphocyte count decreased † 1	4/64 (6.25%)	7	0/63 (0.00%)	0
Neutrophil count decreased † 1	6/64 (9.38%)	25	7/63 (11.11%)	11
Platelet count decreased † 1	8/64 (12.50%)	18	6/63 (9.52%)	11
Weight decreased † 1	5/64 (7.81%)	6	0/63 (0.00%)	0
White blood cell count decreased † 1	10/64 (15.63%)	34	5/63 (7.94%)	10
Metabolism and nutrition disorders
Decreased appetite † 1	29/64 (45.31%)	46	27/63 (42.86%)	44
Hyperglycaemia † 1	4/64 (6.25%)	6	1/63 (1.59%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	4/64 (6.25%)	7	2/63 (3.17%)	3
Back pain † 1	5/64 (7.81%)	13	6/63 (9.52%)	7
Muscle spasms † 1	4/64 (6.25%)	4	1/63 (1.59%)	1
Nervous system disorders
Dizziness † 1	4/64 (6.25%)	4	3/63 (4.76%)	3
Dysgeusia † 1	2/64 (3.13%)	2	4/63 (6.35%)	6
Headache † 1	4/64 (6.25%)	6	3/63 (4.76%)	4
Psychiatric disorders
Insomnia † 1	5/64 (7.81%)	6	1/63 (1.59%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	8/64 (12.50%)	11	7/63 (11.11%)	15
Dyspnoea † 1	12/64 (18.75%)	12	10/63 (15.87%)	14
Epistaxis † 1	5/64 (7.81%)	5	3/63 (4.76%)	4
Haemoptysis † 1	1/64 (1.56%)	2	4/63 (6.35%)	4
Skin and subcutaneous tissue disorders
Dry skin † 1	12/64 (18.75%)	14	5/63 (7.94%)	5
Pruritus † 1	10/64 (15.63%)	13	8/63 (12.70%)	8
Rash † 1	15/64 (23.44%)	29	4/63 (6.35%)	5
Rash maculo-papular † 1	18/64 (28.13%)	46	2/63 (3.17%)	2
Skin hyperpigmentation † 1	18/64 (28.13%)	25	12/63 (19.05%)	12
Vascular disorders
Hypotension † 1	4/64 (6.25%)	4	0/63 (0.00%)	0
1 Term from vocabulary, MedDRA 19.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Taiho Central
• Organization: Taiho Oncology, Inc.
• Phone: 1-609-250-7336
• EMail: clinicaltrialinfo@taihooncology.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Yamamoto N, Hayashi H, Planchard D, Moran T, Gregorc V, Dowell J, Sakai H, Yoh K, Nishio M, Cortot AB, Benhadji KA, Soni N, Huang J, Makris L, Cedres S. A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer. Invest New Drugs. 2020 Oct;38(5):1588-1597. doi: 10.1007/s10637-020-00930-5. Epub 2020 Apr 3.

• Responsible Party: Taiho Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02855125
• Other Study ID Numbers: TAS-114-201; 2016-001806-40 ( EudraCT Number )
• First Submitted: July 18, 2016
• First Posted: August 4, 2016
• Results First Submitted: November 24, 2021
• Results First Posted: December 23, 2021
• Last Update Posted: December 23, 2021