Trial Outcomes & Findings for Study on the Effectiveness and Safety of the Combination of the Two Drugs Regorafenib and Nivolumab in Patients With Colorectal Cancer (Cancer of the Colon or Rectum Classified as Proficient Mismatch Repair and Microsatellite Stable) (NCT NCT04126733)
NCT ID: NCT04126733
Last Updated: 2023-07-18
Results Overview
ORR was defined as the percentage of participants with overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)
Results posted on
2023-07-18
Participant Flow
Study was conducted at 12 centers (of which at least one participant was treated) in the United States between 14-OCT-2019 (first participant first visit) and 28-MAR-2022 (last participant last visit).
A total of 94 participants were screened to enter the study; 21 participants were screening failures and 3 participants discontinued before completion of screening (2 participants withdrew consent and 1 participant died during screening). A total of 70 participants were assigned to treatment and received at least one dose of study treatment.
Participant milestones
| Measure |
Regorafenib Plus Nivolumab
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Treatment Period
STARTED
|
70
|
|
Treatment Period
COMPLETED
|
0
|
|
Treatment Period
NOT COMPLETED
|
70
|
|
Active Follow-up Period
STARTED
|
39
|
|
Active Follow-up Period
COMPLETED
|
19
|
|
Active Follow-up Period
NOT COMPLETED
|
20
|
|
Long-term Follow-up Period
STARTED
|
29
|
|
Long-term Follow-up Period
COMPLETED
|
0
|
|
Long-term Follow-up Period
NOT COMPLETED
|
29
|
Reasons for withdrawal
| Measure |
Regorafenib Plus Nivolumab
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Treatment Period
Progressive Disease - Radiological Progression
|
47
|
|
Treatment Period
Adverse Event
|
8
|
|
Treatment Period
Progressive Disease - Clinical Assessment
|
7
|
|
Treatment Period
Physician Decision
|
5
|
|
Treatment Period
Death
|
1
|
|
Treatment Period
Other Reasons
|
2
|
|
Active Follow-up Period
Death
|
13
|
|
Active Follow-up Period
Progressive Disease - Clinical Assessment
|
4
|
|
Active Follow-up Period
Withdrawal by Subject
|
2
|
|
Active Follow-up Period
Other Reasons
|
1
|
|
Long-term Follow-up Period
Death
|
22
|
|
Long-term Follow-up Period
Withdrawal by Subject
|
1
|
|
Long-term Follow-up Period
Ongoing with Long Term Follow-up
|
6
|
Baseline Characteristics
Study on the Effectiveness and Safety of the Combination of the Two Drugs Regorafenib and Nivolumab in Patients With Colorectal Cancer (Cancer of the Colon or Rectum Classified as Proficient Mismatch Repair and Microsatellite Stable)
Baseline characteristics by cohort
| Measure |
Regorafenib Plus Nivolumab
n=70 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Age, Continuous
|
57.9 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
61 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
50 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
NA Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Baseline ECOG Performance Status
0 - Fully Active
|
36 participants
n=5 Participants
|
|
Baseline ECOG Performance Status
1 - Restricted Activity
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Through database cut-off date of 11-NOV-2020 (Primary Completion Date) (up to 13 months)Population: Full Analysis Set (FAS)
ORR was defined as the percentage of participants with overall response of complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=70 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 Assessed by Investigator
|
7.1 percentage (%) of participants
Interval 2.4 to 15.9
|
SECONDARY outcome
Timeframe: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)Population: Full Analysis Set (FAS)
DOR was defined for responders only as the time from first documentation of response (i.e. CR or PR) until disease progression or death (if death without documented disease progression). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=5 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Duration of Response (DOR)
|
NA weeks
Interval 16.14 to
Median, upper bound for 95% confidence interval could not be calculated due to insufficient number of participants with event.
|
SECONDARY outcome
Timeframe: At 8, 16, 24, 32 and 40 weeksPopulation: Full Analysis Set (FAS)
DCR was defined as the percentage of participants with tumor response of complete response (CR), partial response (PR) or stable disease (SD). CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have decreased in size to have a short axis of \< 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=70 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Disease Control Rate (DCR) at 8 and 16 Weeks
Disease Control Rate at 8 weeks
|
38.6 percentage (%) of participants
Interval 27.2 to 51.0
|
|
Disease Control Rate (DCR) at 8 and 16 Weeks
Disease Control Rate at 16 weeks
|
38.6 percentage (%) of participants
Interval 27.2 to 51.0
|
|
Disease Control Rate (DCR) at 8 and 16 Weeks
Disease Control Rate at 24 weeks
|
38.6 percentage (%) of participants
Interval 27.2 to 51.0
|
|
Disease Control Rate (DCR) at 8 and 16 Weeks
Disease Control Rate at 32 weeks
|
38.6 percentage (%) of participants
Interval 27.2 to 51.0
|
|
Disease Control Rate (DCR) at 8 and 16 Weeks
Disease Control Rate at 40 weeks
|
38.6 percentage (%) of participants
Interval 27.2 to 51.0
|
SECONDARY outcome
Timeframe: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)Population: Full Analysis Set (FAS)
PFS was the time from first dose of study medication to disease progression or death, whichever was earlier.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=70 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Progression-free Survival (PFS)
|
8.00 weeks
Interval 7.86 to 10.57
|
SECONDARY outcome
Timeframe: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)Population: Full Analysis Set (FAS)
OS was defined as time from first dose of the study treatment to death. For patients who did not die, OS was censored at the last time point at which the survival status was known to be alive.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=70 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Overall Survival (OS)
|
51.86 weeks
Interval 30.29 to 69.71
|
SECONDARY outcome
Timeframe: 30 days after last dose of regorafenib and 100 days after last dose of nivolumab until study completion (up to 30 months)Population: Full Analysis Set (FAS)
TEAEs were started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab.). TEAEs were summarized by system organ class (SOC) and preferred term, severity (based on CTCAE v5 grades). Laboratory data considered as AE were graded according to CTCAE v5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=70 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Any AEs
|
69 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Serious AEs
|
34 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 1
|
3 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 2
|
18 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 3
|
38 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 4
|
7 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 5 (death)
|
3 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 1 or 2
|
21 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 3 or 4
|
45 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Worst grade: Grade 3, 4, or 5
|
48 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Grade 5 (death) between Day X+1 and Day 30
|
3 participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Different Severity Types of TEAEs Per Common Terminology Criteria for Adverse Events (CTCAE) v5
Grade 5 (death) between Day 31 and Day 100
|
0 participants
|
POST_HOC outcome
Timeframe: Through last patient last visit (LPLV) at date of 28 MAR 2022 (up to 30 months)Population: Full Analysis Set (FAS)
Duration of stable disease was measured from the start of the treatment until the criteria for progression were met.
Outcome measures
| Measure |
Regorafenib Plus Nivolumab
n=22 Participants
Regorafenib was administrated 2x40 mg once daily (q.d.) on cycle 1 and up to 3x40 mg q.d. from cycle 2 onward for 3 weeks of each 28 days treatment cycle (21 days on/7 days off).
Nivolumab was administrated 480 mg on day 1 of each 28 days treatment cycle (Q4W).
|
|---|---|
|
Duration of Stable Disease
|
29.86 weeks
Interval 15.86 to 32.0
|
Adverse Events
Regorafenib Plus Nivolumab
Serious events: 34 serious events
Other events: 66 other events
Deaths: 40 deaths
Serious adverse events
| Measure |
Regorafenib Plus Nivolumab
n=70 participants at risk
Regorafenib was administrated 2x40mg q.d. (cycle 1) then up to 3x40mg q.d. (from cycle 2 onward) for 3 weeks of each 28 days treatment cycle. Nivolumab was administrated 480mg on day 1 of each 28 days treatment cycle.
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash
|
1.4%
1/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Blood and lymphatic system disorders
Pancytopenia
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Cardiac disorders
Myocardial infarction
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Ascites
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Ileus
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Intestinal perforation
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.9%
2/70 • Number of events 4 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Duodenal stenosis
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Gastrointestinal oedema
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Asthenia
|
2.9%
2/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Pyrexia
|
5.7%
4/70 • Number of events 4 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Hepatobiliary disorders
Bile duct stone
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Hepatobiliary disorders
Hepatitis cholestatic
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Pneumonia
|
7.1%
5/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Pyelonephritis
|
1.4%
1/70 • Number of events 3 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Sepsis
|
5.7%
4/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Septic shock
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Urinary tract infection
|
1.4%
1/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Urosepsis
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Clostridium difficile infection
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Abdominal abscess
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Alanine aminotransferase increased
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Aspartate aminotransferase increased
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Blood bilirubin increased
|
1.4%
1/70 • Number of events 10 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
4.3%
3/70 • Number of events 3 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.4%
1/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
1.4%
1/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.4%
1/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Nervous system disorders
Encephalopathy
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Nervous system disorders
Hemiparesis
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Renal and urinary disorders
Acute kidney injury
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
1.4%
1/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Pemphigoid
|
1.4%
1/70 • Number of events 3 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
1.4%
1/70 • Number of events 1 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Vascular disorders
Hypertension
|
2.9%
2/70 • Number of events 2 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
Other adverse events
| Measure |
Regorafenib Plus Nivolumab
n=70 participants at risk
Regorafenib was administrated 2x40mg q.d. (cycle 1) then up to 3x40mg q.d. (from cycle 2 onward) for 3 weeks of each 28 days treatment cycle. Nivolumab was administrated 480mg on day 1 of each 28 days treatment cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
18.6%
13/70 • Number of events 24 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Endocrine disorders
Hypothyroidism
|
8.6%
6/70 • Number of events 6 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Abdominal distension
|
7.1%
5/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Abdominal pain
|
21.4%
15/70 • Number of events 18 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
7/70 • Number of events 9 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Constipation
|
15.7%
11/70 • Number of events 12 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
14/70 • Number of events 28 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Dry mouth
|
10.0%
7/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Nausea
|
24.3%
17/70 • Number of events 21 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Stomatitis
|
15.7%
11/70 • Number of events 13 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Gastrointestinal disorders
Vomiting
|
17.1%
12/70 • Number of events 17 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Asthenia
|
5.7%
4/70 • Number of events 4 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Chills
|
8.6%
6/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Fatigue
|
42.9%
30/70 • Number of events 50 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Malaise
|
5.7%
4/70 • Number of events 8 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Mucosal inflammation
|
5.7%
4/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Oedema peripheral
|
5.7%
4/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
General disorders
Pyrexia
|
22.9%
16/70 • Number of events 22 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Bronchitis
|
5.7%
4/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Infections and infestations
Urinary tract infection
|
15.7%
11/70 • Number of events 13 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Alanine aminotransferase increased
|
17.1%
12/70 • Number of events 17 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Aspartate aminotransferase increased
|
18.6%
13/70 • Number of events 18 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Blood bilirubin increased
|
24.3%
17/70 • Number of events 32 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Blood lactate dehydrogenase increased
|
7.1%
5/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.7%
4/70 • Number of events 9 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Lipase increased
|
7.1%
5/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Platelet count decreased
|
8.6%
6/70 • Number of events 13 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Weight decreased
|
15.7%
11/70 • Number of events 18 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Investigations
Blood alkaline phosphatase increased
|
14.3%
10/70 • Number of events 15 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Dehydration
|
12.9%
9/70 • Number of events 14 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
7.1%
5/70 • Number of events 8 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
11.4%
8/70 • Number of events 10 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
11.4%
8/70 • Number of events 11 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.7%
11/70 • Number of events 22 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
15.7%
11/70 • Number of events 14 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
8.6%
6/70 • Number of events 11 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Metabolism and nutrition disorders
Decreased appetite
|
30.0%
21/70 • Number of events 36 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.9%
9/70 • Number of events 10 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.3%
10/70 • Number of events 12 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.4%
8/70 • Number of events 8 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Nervous system disorders
Dizziness
|
5.7%
4/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Nervous system disorders
Headache
|
15.7%
11/70 • Number of events 15 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Renal and urinary disorders
Proteinuria
|
7.1%
5/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
17.1%
12/70 • Number of events 13 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
25.7%
18/70 • Number of events 20 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.1%
5/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
7.1%
5/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.0%
7/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.0%
7/70 • Number of events 7 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
27.1%
19/70 • Number of events 31 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.7%
4/70 • Number of events 4 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
7/70 • Number of events 10 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
28.6%
20/70 • Number of events 29 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Vascular disorders
Hypertension
|
15.7%
11/70 • Number of events 14 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
|
Vascular disorders
Hypotension
|
7.1%
5/70 • Number of events 5 • An adverse event (AE) was considered as treatment-emergent (TEAE) if it started during treatment or within the post-treatment time window (30 days after last dose of regorafenib and 100 days after last dose of nivolumab) until study completion (up to 30 months).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators may publish or present individual study data (including case reports) obtained in the course of this study but only after the primary report and/or publication of the study results in their entirety. If publishing individual site data is foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
- Publication restrictions are in place
Restriction type: OTHER