A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC

• ClinicalTrials.gov Identifier: NCT02860546
• Recruitment Status: Completed
• First Posted: August 9, 2016
• Results First Posted: July 26, 2021
• Last Update Posted: July 26, 2021
• Sponsor: Taiho Oncology, Inc.
• Information provided by (Responsible Party): Taiho Oncology, Inc.

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Refractory Metastatic Colorectal Cancer
• Interventions: Drug: TAS-102; Drug: nivolumab
• Enrollment: 18

Participant Flow

Recruitment Details	The study was conducted at 3 centers in United States.
Pre-assignment Details	A total of 22 participants were screened out of which 18 participants passed the screening and were enrolled in the study. This study was planned to have 2 stages but only stage1 was completed. The study was halted following an interim analysis and no participants were enrolled in stage 2. Therefore, the data represented is for stage 1 only.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description	Participants received a dose of 35 milligrams per meter square (mg/m^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Period Title: Overall Study
Started	18
Completed	0
Not Completed	18
Reason Not Completed
Clinical Progression	6
Radiological Progression	12

Baseline Characteristics

Arm/Group Title		TAS-102 + Nivolumab
Arm/Group Description		Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Baseline Participants		18
Baseline Analysis Population Description		Baseline population included all enrolled participants who received at least 1 dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	18 participants
		58.0 (7.32)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	Female	9 50.0%
	Male	9 50.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	18 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	4 22.2%
	White	12 66.7%
	More than one race	0 0.0%
	Unknown or Not Reported	2 11.1%

Outcome Measures

1. Primary Outcome

Title	Immune-Related Overall Response Rate (irORR)
Description	irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir.
Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants in the safety population (all participants who received at least 1 dose of study drug) who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: percentage of participants
	0

2. Secondary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs)
Description	DLT: defined as occurrence of any of the following- Hematological toxicities: Grade 4 neutropenia lasting greater than(>)7 days; Grade 4 febrile neutropenia and fever greater than or equal to (>=)38 degree celsius for over 1 hour; Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding or requiring transfusions Non-hematological toxicities: Grade 3 or grade 4 non-hematologic toxicity (excluding alopecia, nausea, vomiting, diarrhea); Grade 3 or grade 4 nausea/vomiting lasting >48 hours and uncontrolled by aggressive anti-emetic therapy, including serotonin 5-HT3 receptor antagonists (e.g, ondansetron); Grade 3 or grade 4 diarrhea lasting > 48 hours and unresponsive to antidiarrheal medication Drug-related toxicities: Any drug-related toxicity resulting in > 2 weeks delay in initiation of Cycle 2 (i.e, cannot start Cycle 2 until Day 43 or later); Any drug-related toxicity that prevents completion of 80% compliance for either drug in Cycle 1
Time Frame	Cycle 1 (each cycle is of 4 weeks)

Outcome Measure Data

Analysis Population Description

DLT Evaluable (DLTE) population included all participants in the safety population in Stage 1, prior to confirming the recommended dose, who completed at least 1 cycle (28 days) of study treatment with at least 80% of the study treatment administered, unless the treatment was interrupted because of a DLT.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	6
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

3. Secondary Outcome

Title	Recommended Phase 2 Dose (RP2D)
Description	RP2D of TAS-102 was evaluated based on the safety and tolerability of the combination therapy of TAS-102 and Nivolumab.
Time Frame	Cycle 1 (each cycle is of 4 weeks)

Outcome Measure Data

Analysis Population Description

DLTE population included all participants in the safety population in Stage 1, prior to confirming the recommended dose, who completed at least 1 cycle (4 weeks) of study treatment with at least 80% of the study treatment administered, unless the treatment was interrupted because of a DLT.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	6
Measure Type: Number; Unit of Measure: mg/m^2
	35

4. 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: AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: participants
Participants with TEAEs	18
Participants with TESAEs	6

5. Secondary Outcome

Title	Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Description	Hematological and chemistry laboratory tests abnormalities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).
Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: participants
Grade 4: Neutropenia (neutrophils low)	3
Grade 4: Anemia (hemoglobin low)	1
Grade 4: Leukopenia (leukocytes low)	0
Grade 4: Lymphopenia (lymphocytes low)	0
Grade 4: Thrombocytopenia (platelets low)	0
Grade 4: Bilirubin High	0
Grade 4: Glucose High	0
Grade 4: Sodium Low	0
Grade 3: Neutropenia (neutrophils low)	3
Grade 3: Anemia (hemoglobin low)	1
Grade 3: Leukopenia (leukocytes low)	6
Grade 3: Lymphopenia (lymphocytes low)	2
Grade 3: Thrombocytopenia (platelets low)	1
Grade 3: Bilirubin High	1
Grade 3: Glucose High	1
Grade 3: Sodium Low	1

6. Secondary Outcome

Title	Overall Response Rate (ORR)
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. Any pathological lymph nodes must have reduction in short axis to less than (<)10 millimeters (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.
Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Measure Type: Number; Unit of Measure: percentage of participants
	0

7. Secondary Outcome

Title	Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC)
Description	Immune-related progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on irRC) or death due to any cause. Participants who were alive with no disease progression at the moment of the analysis cut-off date was censored at the date of the last tumor assessment. Per irRC criteria disease progression defined as at least 25% increase in SPD relative to nadir. Analysis was performed using Kaplan-Meier estimates.
Time Frame	From the first dose of study treatment to disease progression or death (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Median (95% Confidence Interval); Unit of Measure: months
Radiologic progression of disease only	2.2; (1.8 to 6.0)
Radiologic + clinical progression of disease	2.2; (1.8 to 3.7)

8. Secondary Outcome

Title	Progression-Free Survival (PFS) Based on RECIST Criteria
Description	Progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on RECIST 1.1) or death due to any cause. Per RECIST criteria disease progression defined as least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study, including the baseline sum. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Definitive new lesion presence also indicated progression.
Time Frame	From the first dose of study treatment to disease progression or death (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Median (95% Confidence Interval); Unit of Measure: months
Radiologic progression of disease only	2.8; (1.8 to 5.1)
Radiologic + clinical progression of disease	2.5; (1.8 to 3.7)

9. Secondary Outcome

Title	Disease Control Rate (DCR) Based on irRC Criteria
Description	DCR was defined as the percentage of participants with objective evidence of radiologic complete response (CR), partial response (PR), or stable disease (SD) and was based on the overall best response from each participant as determined from investigator response assessments and following irRC criteria. Per irRC criteria, CR was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions). PR was defined as a decrease in the sum of the products of the two largest perpendicular diameters by 50% or greater by a consecutive assessment at least 4 weeks after first documentation. SD was defined as the failure to meet criteria for irCR or irPR in absence of in absence of irPD.
Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	44.4; (21.5 to 69.2)

10. Secondary Outcome

Title	Disease Control Rate (DCR) Based on RECIST Criteria
Description	DCR was defined as the percentage of participants with objective evidence of radiologic CR, PR, or SD and was based on the overall best response from each participant as determined from investigator response assessments and following RECIST Criteria version 1.1. Per RECIST Criteria CR defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to <10 mm. PR 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 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 first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	18
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	55.6; (30.8 to 78.5)

11. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the first dose of the study treatment to the death in the safety population. Participants alive at the time of the study discontinuation were censored. Analysis was performed using Kaplan-Meier estimates.
Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed is 0 because data were not collected for the outcome measure at particular time point.

Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description:	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Adverse Event Reporting Description	Analysis was performed on safety population.
Arm/Group Title	TAS-102 + Nivolumab
Arm/Group Description	Participants received a dose of 35 mg/m^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
All-Cause Mortality
	TAS-102 + Nivolumab
	Affected / at Risk (%)
Total	0/18 (0.00%)
Serious Adverse Events
	TAS-102 + Nivolumab
	Affected / at Risk (%)	# Events
Total	6/18 (33.33%)
Gastrointestinal disorders
Abdominal pain † 1	2/18 (11.11%)	2
Colitis † 1	1/18 (5.56%)	1
Diarrhoea † 1	1/18 (5.56%)	1
Nausea † 1	2/18 (11.11%)	3
Vomiting † 1	1/18 (5.56%)	3
General disorders
Pyrexia † 1	1/18 (5.56%)	1
Hepatobiliary disorders
Cholangitis † 1	1/18 (5.56%)	1
Infections and infestations
Urinary tract infection † 1	1/18 (5.56%)	1
Psychiatric disorders
Confusional state † 1	1/18 (5.56%)	1
Renal and urinary disorders
Obstructive uropathy † 1	1/18 (5.56%)	1
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	TAS-102 + Nivolumab
	Affected / at Risk (%)	# Events
Total	18/18 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	5/18 (27.78%)	11
Lymphadenopathy † 1	1/18 (5.56%)	1
Neutropenia † 1	3/18 (16.67%)	5
Thrombocytopenia † 1	2/18 (11.11%)	2
Ear and labyrinth disorders
Tinnitus † 1	1/18 (5.56%)	1
Eye disorders
Lacrimation increased † 1	1/18 (5.56%)	1
Photopsia † 1	1/18 (5.56%)	1
Gastrointestinal disorders
Abdominal distension † 1	1/18 (5.56%)	1
Abdominal pain † 1	5/18 (27.78%)	6
Abdominal pain upper † 1	2/18 (11.11%)	2
Ascites † 1	1/18 (5.56%)	1
Constipation † 1	4/18 (22.22%)	5
Diarrhoea † 1	11/18 (61.11%)	22
Dyspepsia † 1	1/18 (5.56%)	1
Nausea † 1	12/18 (66.67%)	25
Proctalgia † 1	1/18 (5.56%)	1
Stomatitis † 1	2/18 (11.11%)	2
Vomiting † 1	6/18 (33.33%)	9
General disorders
Asthenia † 1	2/18 (11.11%)	2
Fatigue † 1	6/18 (33.33%)	14
Mucosal inflammation † 1	2/18 (11.11%)	6
Oedema peripheral † 1	1/18 (5.56%)	1
Pyrexia † 1	2/18 (11.11%)	2
Infections and infestations
Candida infection † 1	1/18 (5.56%)	1
Herpes zoster † 1	1/18 (5.56%)	1
Influenza † 1	1/18 (5.56%)	1
Oral herpes † 1	1/18 (5.56%)	1
Sinusitis † 1	1/18 (5.56%)	1
Upper respiratory tract infection † 1	2/18 (11.11%)	2
Urinary tract infection † 1	2/18 (11.11%)	2
Injury, poisoning and procedural complications
Medication error † 1	1/18 (5.56%)	1
Investigations
Alanine aminotransferase increased † 1	1/18 (5.56%)	1
Blood bilirubin increased † 1	2/18 (11.11%)	4
Neutrophil count decreased † 1	6/18 (33.33%)	14
Platelet count decreased † 1	1/18 (5.56%)	2
Metabolism and nutrition disorders
Decreased appetite † 1	3/18 (16.67%)	3
Hyponatraemia † 1	1/18 (5.56%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/18 (5.56%)	1
Bone pain † 1	1/18 (5.56%)	1
Musculoskeletal chest pain † 1	1/18 (5.56%)	1
Nervous system disorders
Dizziness † 1	1/18 (5.56%)	1
Sciatica † 1	1/18 (5.56%)	2
Psychiatric disorders
Insomnia † 1	1/18 (5.56%)	1
Renal and urinary disorders
Chromaturia † 1	1/18 (5.56%)	1
Dysuria † 1	2/18 (11.11%)	2
Reproductive system and breast disorders
Vaginal discharge † 1	1/18 (5.56%)	1
Vulvovaginal dryness † 1	1/18 (5.56%)	1
Vulvovaginal pain † 1	1/18 (5.56%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	1/18 (5.56%)	1
Dyspnoea † 1	3/18 (16.67%)	3
Nasal congestion † 1	2/18 (11.11%)	2
Respiratory tract congestion † 1	1/18 (5.56%)	1
Rhinorrhoea † 1	2/18 (11.11%)	2
Skin and subcutaneous tissue disorders
Alopecia † 1	1/18 (5.56%)	1
Erythema † 1	1/18 (5.56%)	1
Hyperhidrosis † 1	1/18 (5.56%)	1
Pruritus † 1	4/18 (22.22%)	4
Rash † 1	1/18 (5.56%)	1
Rash follicular † 1	2/18 (11.11%)	2
Rash maculo-papular † 1	2/18 (11.11%)	2
Vascular disorders
Flushing † 1	1/18 (5.56%)	1
Hypertension † 1	2/18 (11.11%)	2
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

After interim analysis, per study design plan, the trial was stopped for futility before enrollment into Stage 2.

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: 609-250-7336
• EMail: clinicaltrialinfo@taihooncology.com

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

Patel MR, Falchook GS, Hamada K, Makris L, Bendell JC. A phase 2 trial of trifluridine/tipiracil plus nivolumab in patients with heavily pretreated microsatellite-stable metastatic colorectal cancer. Cancer Med. 2021 Feb;10(4):1183-1190. doi: 10.1002/cam4.3630. Epub 2021 Feb 5.

• Responsible Party: Taiho Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02860546
• Other Study ID Numbers: TAS-102-203
• First Submitted: July 13, 2016
• First Posted: August 9, 2016
• Results First Submitted: July 2, 2021
• Results First Posted: July 26, 2021
• Last Update Posted: July 26, 2021