Trial Outcomes & Findings for E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck (NCT NCT01332266)
NCT ID: NCT01332266
Last Updated: 2022-01-03
Results Overview
DLT:adverse events graded as NCI CTCAEv4.0 occurring less than or equal to(\<=)28 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(\>=)3 peripheral neuropathy; 2)Grade 3 fatigue or 2 point decline in eastern cooperative oncology group performance status that persisted for greater than(\>)7 days; 3)Grade \>=3 nausea,vomiting despite optimal antiemetic treatment; 4)Any nonhematologic toxicity of Grade \>=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological 1)Grade 4 neutropenia lasting \>7 days; 2)Febrile neutropenia as fever \>=38.5 degree celsius with absolute neutrophil count less than(\<)1.0\*10\^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
95 participants
Primary outcome timeframe
Cycle 1 (Cycle length is equal to [=] 28 days)
Results posted on
2022-01-03
Participant Flow
Participants took part in the study at 28 investigative sites in the Republic of Korea, Ukraine, United Kingdom, and the United States from 19 September 2011 to 04 September 2017.
This study consists of two phases Phase 1b and Phase 2. Phase 1b: 12 participants were enrolled and received the study treatment; Phase 2: 83 participants were enrolled and received the study treatment.
Participant milestones
| Measure |
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant squamous cell carcinoma of the head and neck (SCCHN) received golvatinib 200 milligram (mg) tablets, orally, once daily (run-in period) and cetuximab 400 milligram per square meter (mg/m\^2) intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D), until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 2: Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|---|---|
|
Phase 1b
STARTED
|
4
|
5
|
3
|
0
|
0
|
|
Phase 1b
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Phase 1b
NOT COMPLETED
|
4
|
5
|
3
|
0
|
0
|
|
Phase 2
STARTED
|
0
|
0
|
0
|
42
|
41
|
|
Phase 2
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Phase 2
NOT COMPLETED
|
0
|
0
|
0
|
42
|
41
|
Reasons for withdrawal
| Measure |
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant squamous cell carcinoma of the head and neck (SCCHN) received golvatinib 200 milligram (mg) tablets, orally, once daily (run-in period) and cetuximab 400 milligram per square meter (mg/m\^2) intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D), until the occurrence of progressive disease (PD), unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 2: Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|---|---|
|
Phase 1b
Death
|
3
|
3
|
2
|
0
|
0
|
|
Phase 1b
Lost to Follow-up
|
0
|
1
|
0
|
0
|
0
|
|
Phase 1b
Withdrawal by Subject
|
1
|
1
|
1
|
0
|
0
|
|
Phase 2
Death
|
0
|
0
|
0
|
33
|
36
|
|
Phase 2
Lost to Follow-up
|
0
|
0
|
0
|
2
|
0
|
|
Phase 2
Physician Decision
|
0
|
0
|
0
|
3
|
1
|
|
Phase 2
Symptomatic deterioration
|
0
|
0
|
0
|
0
|
1
|
|
Phase 2
Progression Disease
|
0
|
0
|
0
|
2
|
1
|
|
Phase 2
Withdrawal by Subject
|
0
|
0
|
0
|
2
|
2
|
Baseline Characteristics
E7050 in Combination With Cetuximab Versus Cetuximab Alone in the Treatment of Platinum-Resistant Squamous Cell Carcinoma of the Head and Neck
Baseline characteristics by cohort
| Measure |
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2
n=4 Participants
Participants with platinum-resistant SCCHN received golvatinib 200 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2
n=5 Participants
Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=3 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Total
n=95 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
70.0 years
STANDARD_DEVIATION 8.29 • n=5 Participants
|
58.8 years
STANDARD_DEVIATION 12.58 • n=7 Participants
|
59.3 years
STANDARD_DEVIATION 5.51 • n=5 Participants
|
58.4 years
STANDARD_DEVIATION 11.04 • n=4 Participants
|
53.9 years
STANDARD_DEVIATION 9.84 • n=21 Participants
|
57.0 years
STANDARD_DEVIATION 10.79 • n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
13 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
38 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
82 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
41 Participants
n=4 Participants
|
41 Participants
n=21 Participants
|
93 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
36 Participants
n=8 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
29 Participants
n=21 Participants
|
56 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: 0 (Fully Active)
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
21 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: 1 (Restricted in Physical Activity; Ambulatory)
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
62 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: 2 (Ambulatory and Capable of All Self-care)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
5 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: 3 (Capable of Only Limited Self-care)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: 4 (Completely Disabled)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
ECOG: 5 (Dead)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Not Specified
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 (Cycle length is equal to [=] 28 days)Population: Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.
DLT:adverse events graded as NCI CTCAEv4.0 occurring less than or equal to(\<=)28 days after treatment.Events as: Non-hematological: 1)Grade greater than or equal to(\>=)3 peripheral neuropathy; 2)Grade 3 fatigue or 2 point decline in eastern cooperative oncology group performance status that persisted for greater than(\>)7 days; 3)Grade \>=3 nausea,vomiting despite optimal antiemetic treatment; 4)Any nonhematologic toxicity of Grade \>=3, with exceptions as alopecia,single laboratory values out of normal range,hypersensitivity reaction. Hematological 1)Grade 4 neutropenia lasting \>7 days; 2)Febrile neutropenia as fever \>=38.5 degree celsius with absolute neutrophil count less than(\<)1.0\*10\^9 per liter(/L); 3)Grade 3 thrombocytopenia with nontraumatic bleeding requiring platelet transfusion; 4)Grade 4 thrombocytopenia with/without nontraumatic bleeding. Other 1)Study drug related death; 2)Toxicity that dose escalation committee believed to be DLT that was not covered by above DLT criteria.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=5 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=4 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=3 Participants
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Cycle 1: 0-48 hours post-dose (Each cycle=28 days)Population: Data was not collected and analyzed for this outcome measure because no pharmacokinetic analysis was conducted in this study due to incomplete pharmacokinetic sample bioanalysis due to unresolved queries leading to inadequate calculations and limited data interpretability.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 5 years 11 monthsPopulation: Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.
TEAEs are defined as an adverse event that has an onset date, or a worsening in severity from baseline (pre-golvatinib), on or after the first dose of golvatinib. The severity was graded according to CTCAE v4.0. 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 (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to adverse event.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Number of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)
|
21 Participants
|
21 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years 4 monthsPopulation: Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Number of Participants With Markedly Abnormal Vital Sign Values
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years 4 monthsPopulation: Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.
Physical examination was performed and included evaluation of 1) General appearance, 2) Head; Eyes; Ears; Nose; Throat (HEENT), 3) Neck, 4) Heart, 5) Chest (Including Lungs), 6) Abdomen, 7) Extremities, 8) Skin, 9) Lymph Nodes, and 10) neurological status. Here, number of participants with markedly abnormal physical examinations were reported.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Skin
|
5 Participants
|
4 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Lymph Nodes
|
15 Participants
|
13 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Chest (Including Lungs)
|
5 Participants
|
4 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Abdomen
|
3 Participants
|
6 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Extremities
|
0 Participants
|
2 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
General Appearance
|
6 Participants
|
5 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
HEENT
|
17 Participants
|
20 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Neck
|
22 Participants
|
24 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Heart
|
0 Participants
|
1 Participants
|
—
|
|
Phase 2: Number of Participants With Markedly Abnormal Physical Examinations Findings
Neurologic
|
5 Participants
|
3 Participants
|
—
|
PRIMARY outcome
Timeframe: Up to 4 years 4 monthsPopulation: Safety population was defined as all participants enrolled and randomized to treatment in study, except for those who drop out of the study prior to receiving any study treatment, or were without any safety assessments following the first dose of study treatment.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Values
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: From the date of randomization until the earlier of the following two events: the date of PD or the date of death (Up to approximately 4 years 4 months)Population: Modified Intent-to-Treat (MITT) analysis set included all participants randomized in the applicable study arm who received any comparator or study drug.
PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on response evaluation criteria in solid tumor (RECIST) v1.1. PD is defined as at least a 20 percent (%) increase or 5 millimeter (mm) increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Progression-free Survival (PFS)
|
15.71 weeks
Interval 9.29 to 18.71
|
15.71 weeks
Interval 12.14 to 23.86
|
—
|
SECONDARY outcome
Timeframe: At Week 12Population: MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug.
PFS rate at week 12 is defined as the percentage of participants who were still alive without disease progression at 12 weeks from the date of randomization. PFS is defined as the time from the date of randomization until the earlier of the following two events: the date of PD or the date of death based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. PFS rate was estimated and analyzed using Kaplan Meier method.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Percentage of Participants With PFS at Week 12
|
59.4 percentage of participants
Interval 41.9 to 73.23
|
68.9 percentage of participants
Interval 50.79 to 81.44
|
—
|
SECONDARY outcome
Timeframe: From the date of randomization until the date of PD (Up to approximately 4 years 4 months)Population: MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug.
TTP is defined as the time from the date of randomization until the date of PD based on RECIST v1.1. PD is defined as at least a 20% increase or 5 mm increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions. TTP was estimated and analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Time to Progression (TTP)
|
16.00 weeks
Interval 9.29 to 19.14
|
15.43 weeks
Interval 12.14 to 23.14
|
—
|
SECONDARY outcome
Timeframe: From the date of randomization until the date of death (Up to approximately 4 years 4 months)Population: MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug. Here "Overall number of participants analyzed" signifies participants with events (death).
OS is defined as the time from the date of randomization until the date of death. OS was analyzed using Kaplan Meier method. As planned, data for this endpoint was analyzed and collected till primary completion date.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=36 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=33 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Overall Survival (OS)
|
36.71 weeks
Interval 28.0 to 44.43
|
39.71 weeks
Interval 28.43 to 49.71
|
—
|
SECONDARY outcome
Timeframe: From the date of randomization until CR or PR (Up to approximately 4 years 4 months)Population: MITT analysis set included all participants randomized in the applicable study arm who received any comparator or study drug.
Overall response rate is defined as percentage of participants with complete response (CR) or partial response (PR) based on RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. As planned, data for this endpoint was analyzed and collected till primary completion date.
Outcome measures
| Measure |
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 Participants
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 Participants
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Participants with platinum-resistant SCCHN received 400 mg of golvatinib tablets orally, once daily (run-in period) and Cetuximab 400 mg/m\^2 as intravenous infusion, once on day 1 of cycle 1, followed by 250 mg/m\^2 as intravenous infusion, once on days 8, 15 and 22 of cycle 1 of 28-days treatment cycle for 6 subsequent cycles until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|
|
Phase 2: Percentage of Participants With Overall Response
|
4.9 percentage of participants
Interval 0.0 to 11.5
|
9.5 percentage of participants
Interval 0.7 to 18.4
|
—
|
Adverse Events
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2
Serious events: 1 serious events
Other events: 4 other events
Deaths: 3 deaths
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2
Serious events: 4 serious events
Other events: 5 other events
Deaths: 3 deaths
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Serious events: 2 serious events
Other events: 3 other events
Deaths: 2 deaths
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
Serious events: 15 serious events
Other events: 42 other events
Deaths: 33 deaths
Phase 2: Arm 2: Cetuximab 400 mg/m^2
Serious events: 15 serious events
Other events: 38 other events
Deaths: 36 deaths
Serious adverse events
| Measure |
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2
n=4 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 200 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2
n=5 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=3 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 participants at risk
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Cellulitis
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Pneumonia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
4.8%
2/42 • Number of events 2 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper Airway Obstruction
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Haemorrhage Subcutaneous
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Cardiac disorders
Pericardial Effusion
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
4.8%
2/42 • Number of events 2 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Mechanical Ileus
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Oral Cavity Fistula
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
General disorders
Adverse Drug Reaction
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Infections and infestations
Pyelonephritis Acute
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Infections and infestations
Staphylococcal Infection
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Tuberculosis
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Injury, poisoning and procedural complications
Alcohol Poisoning
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Injury, poisoning and procedural complications
Post Procedural Haemorrhage
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Pain In Jaw
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Haemorrhage
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 3 • Up to 5 years 11 months
|
|
Nervous system disorders
Depressed Level Of Consciousness
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Nervous system disorders
Presyncope
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 2 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Stridor
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Vascular disorders
Hypotension
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
Other adverse events
| Measure |
Phase 1b: Cohort 1: Golvatinib 200 mg + Cetuximab 400 mg/m^2
n=4 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 200 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 2: Golvatinib 300 mg + Cetuximab 400 mg/m^2
n=5 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 300 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 1b: Cohort 3: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=3 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 400 mg tablets, orally, once daily (run-in period) and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles for determining MTD or RP2D, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 1: Golvatinib 400 mg + Cetuximab 400 mg/m^2
n=42 participants at risk
Participants with platinum-resistant SCCHN received golvatinib 400 mg (RP2D) tablets, orally, once daily and cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by cetuximab 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
Phase 2: Arm 2: Cetuximab 400 mg/m^2
n=41 participants at risk
Participants with platinum-resistant SCCHN received cetuximab 400 mg/m\^2 intravenous infusion, once on Day 1 of Cycle 1, followed by 250 mg/m\^2 intravenous infusion, once on Days 8, 15 and 22 of Cycle 1 in a 28-days treatment cycle for up to 6 subsequent cycles. After 6 cycles, at the discretion of the Investigator, participants who experienced clinical benefit could continue for as long as clinical benefit was sustained and the treatment was well tolerated, until the occurrence of PD, unacceptable toxicity, withdrawal of consent, withdrawal by the Investigator, lost to follow-up, or death, whichever occurred first.
|
|---|---|---|---|---|---|
|
Investigations
Protein Total Decreased
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
9.5%
4/42 • Number of events 8 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Investigations
Alanine Aminotransferase Increased
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 9 • Up to 5 years 11 months
|
23.8%
10/42 • Number of events 12 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 2 • Up to 5 years 11 months
|
45.2%
19/42 • Number of events 35 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
0.00%
0/4 • Up to 5 years 11 months
|
60.0%
3/5 • Number of events 4 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Investigations
Blood Lactate Dehydrogenase Increased
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Blood and lymphatic system disorders
Anaemia
|
50.0%
2/4 • Number of events 4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
9.5%
4/42 • Number of events 5 • Up to 5 years 11 months
|
12.2%
5/41 • Number of events 6 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Constipation
|
25.0%
1/4 • Number of events 2 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 2 • Up to 5 years 11 months
|
23.8%
10/42 • Number of events 13 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Diarrhoea
|
50.0%
2/4 • Number of events 2 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
23.8%
10/42 • Number of events 22 • Up to 5 years 11 months
|
9.8%
4/41 • Number of events 4 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Dyspepsia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Dysphagia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
11.9%
5/42 • Number of events 6 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 3 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 2 • Up to 5 years 11 months
|
23.8%
10/42 • Number of events 10 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 3 • Up to 5 years 11 months
|
|
General disorders
Asthenia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
11.9%
5/42 • Number of events 5 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Eye disorders
Blepharitis
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
General disorders
Chest Pain
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
50.0%
2/4 • Number of events 2 • Up to 5 years 11 months
|
40.0%
2/5 • Number of events 2 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
23.8%
10/42 • Number of events 12 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
|
75.0%
3/4 • Number of events 6 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 3 • Up to 5 years 11 months
|
23.8%
10/42 • Number of events 17 • Up to 5 years 11 months
|
17.1%
7/41 • Number of events 9 • Up to 5 years 11 months
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 2 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
75.0%
3/4 • Number of events 4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Erythema
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
General disorders
Face Oedema
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
General disorders
Fatigue
|
25.0%
1/4 • Number of events 2 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
11.9%
5/42 • Number of events 5 • Up to 5 years 11 months
|
12.2%
5/41 • Number of events 5 • Up to 5 years 11 months
|
|
Vascular disorders
Flushing
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Renal and urinary disorders
Haematuria
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
4.8%
2/42 • Number of events 2 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • Number of events 3 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
50.0%
2/4 • Number of events 2 • Up to 5 years 11 months
|
40.0%
2/5 • Number of events 2 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 2 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
40.0%
2/5 • Number of events 2 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
50.0%
2/4 • Number of events 3 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
4.8%
2/42 • Number of events 3 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 5 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
50.0%
2/4 • Number of events 2 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 6 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
General disorders
Localised Oedema
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Ulcer
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Investigations
Neutrophil Count Decreased
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
General disorders
Oedema Peripheral
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Paronychia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
9.5%
4/42 • Number of events 10 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
General disorders
Pyrexia
|
25.0%
1/4 • Number of events 2 • Up to 5 years 11 months
|
40.0%
2/5 • Number of events 2 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 2 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
66.7%
2/3 • Number of events 3 • Up to 5 years 11 months
|
45.2%
19/42 • Number of events 22 • Up to 5 years 11 months
|
19.5%
8/41 • Number of events 9 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Skin Fissures
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
9.5%
4/42 • Number of events 5 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Skin Ulcer
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
14.3%
6/42 • Number of events 7 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Investigations
Weight Decreased
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
14.3%
6/42 • Number of events 6 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
11.9%
5/42 • Number of events 7 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
General disorders
Mucosal Inflammation
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
9.5%
4/42 • Number of events 6 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
9.5%
4/42 • Number of events 5 • Up to 5 years 11 months
|
12.2%
5/41 • Number of events 12 • Up to 5 years 11 months
|
|
Psychiatric disorders
Depression
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Nervous system disorders
Lethargy
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 2 • Up to 5 years 11 months
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
2.4%
1/41 • Number of events 1 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Oral Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 3 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 3 • Up to 5 years 11 months
|
|
Skin and subcutaneous tissue disorders
Onychomadesis
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Investigations
Eastern Cooperative Oncology Group Performance Status Worsened
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
2.4%
1/42 • Number of events 1 • Up to 5 years 11 months
|
7.3%
3/41 • Number of events 3 • Up to 5 years 11 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
7.1%
3/42 • Number of events 4 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
33.3%
14/42 • Number of events 19 • Up to 5 years 11 months
|
4.9%
2/41 • Number of events 2 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Anal pruritus
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Infections and infestations
Candida infection
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/4 • Up to 5 years 11 months
|
20.0%
1/5 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Ear and labyrinth disorders
Otorrhoea
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/4 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
33.3%
1/3 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Eye disorders
Pinguecula
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Psychiatric disorders
Substance-induced psychotic disorder
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
25.0%
1/4 • Number of events 1 • Up to 5 years 11 months
|
0.00%
0/5 • Up to 5 years 11 months
|
0.00%
0/3 • Up to 5 years 11 months
|
0.00%
0/42 • Up to 5 years 11 months
|
0.00%
0/41 • Up to 5 years 11 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place