Trial Outcomes & Findings for A Randomized Phase 2 Trial of TAS-114 in Combination With S-1 Versus S-1 (NCT NCT02855125)

Last Updated: 2024-09-19

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

128 participants

Primary outcome timeframe

From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)

Results posted on

2024-09-19

Participant Flow

The study was conducted at 26 centers in 5 countries.

A total of 128 participants were randomized.1 participant in S-1 (Monotherapy) arm was randomized but not treated.

Participant milestones

Participant milestones
Measure	TAS-114 + S-1 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).	S-1 (Monotherapy) 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 Study STARTED	64	64
Overall Study Treated	64	63
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	64	64

Reasons for withdrawal

Reasons for withdrawal
Measure	TAS-114 + S-1 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).	S-1 (Monotherapy) 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 Study Withdrawal by Subject	2	2
Overall Study Clinical Disease Progression	5	4
Overall Study Radiologic Disease Progression	36	39
Overall Study Adverse Event	11	7
Overall Study Physician Decision	1	0
Overall Study On Treatment	9	11
Overall Study Randomized but not treated	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TAS-114 + S-1 n=64 Participants 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).	S-1 (Monotherapy) n=64 Participants 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 n=128 Participants Total of all reporting groups
Age, Continuous	63.8 years STANDARD_DEVIATION 7.77 • n=5 Participants	62.6 years STANDARD_DEVIATION 10.22 • n=7 Participants	63.2 years STANDARD_DEVIATION 9.06 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	16 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	48 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	47 Participants n=7 Participants	92 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	30 Participants n=5 Participants	30 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of randomization or until date of disease progression or death whichever occurred first (approximately up to 13 months)

Population: 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.

Outcome measures

Outcome measures
Measure	TAS-114 + S-1 n=64 Participants 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).	S-1 (Monotherapy) n=64 Participants 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).
Progression-free Survival (PFS) Based on Central Independent Review	3.65 months Interval 2.69 to 5.16	4.17 months Interval 2.6 to 6.6

SECONDARY outcome

Timeframe: From date of randomization until death (approximately up to 15 months)

Population: ITT population.

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.

Outcome measures

Outcome measures
Measure	TAS-114 + S-1 n=64 Participants 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).	S-1 (Monotherapy) n=64 Participants 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 Survival (OS)	7.92 months Interval 6.28 to 10.78	9.82 months Interval 7.66 to 13.4

SECONDARY outcome

Timeframe: From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	TAS-114 + S-1 n=61 Participants 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).	S-1 (Monotherapy) n=58 Participants 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 Response Rate (ORR) Based on Central Independent Review	19.7 percentage of participants Interval 10.6 to 31.8	10.3 percentage of participants Interval 3.9 to 21.2

SECONDARY outcome

Timeframe: From date of first dose of study drug to the date of first documentation of progression or death (approximately up to 13 months)

Population: TR population.

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.

Outcome measures

Outcome measures
Measure	TAS-114 + S-1 n=61 Participants 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).	S-1 (Monotherapy) n=58 Participants 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).
Disease Control Rate (DCR) Based on Central Independent Review	80.3 percentage of participants Interval 68.2 to 89.4	75.9 percentage of participants Interval 62.8 to 86.1

SECONDARY outcome

Timeframe: From date of first response to the date of first documentation of progression or death (approximately up to 13 months)

Population: TR population.

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.

Outcome measures

Outcome measures
Measure	TAS-114 + S-1 n=12 Participants 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).	S-1 (Monotherapy) n=6 Participants 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).
Duration of Response (DR) Based on Central Independent Review	3.38 months Interval 2.37 to 4.86	NA months Interval 2.79 to Median and upper limit of 95% Confidence interval were not estimable because of censoring in 5 of the 6 participants.

SECONDARY outcome

Timeframe: From first dose of study drug up to 30 days after the last dose of study drug (approximately up to 13 months)

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

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.

Outcome measures

Outcome measures
Measure	TAS-114 + S-1 n=64 Participants 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).	S-1 (Monotherapy) n=63 Participants 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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Participants with TEAEs	64 Participants	61 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Participants with TESAEs	30 Participants	19 Participants

Adverse Events

TAS-114 + S-1

Serious events: 30 serious events

Other events: 64 other events

Deaths: 36 deaths

S-1 (Monotherapy)

Serious events: 19 serious events

Other events: 61 other events

Deaths: 29 deaths

Serious adverse events

Other adverse events

Additional Information

Taiho Central

Taiho Oncology, Inc.

Phone: +1 844-878-2446

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place