Trial Outcomes & Findings for A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer (NCT NCT01767857)

Last Updated: 2021-06-29

Results Overview

Overall survival time was defined as the duration from the date of randomization until death or last follow-up. OS was summarized by Kaplan-Meier method and compared between the treatment groups using un-adjusted log-rank test.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

643 participants

Primary outcome timeframe

Up to 18 months

Results posted on

2021-06-29

Participant Flow

Total 643 participants were screened and enrolled in the study. Out of them, only 611 participants have received the study drug and participated in the study while 32 participants never received any study drug.

Participant milestones

Participant milestones
Measure	Xilonix Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Overall Study STARTED	430	213
Overall Study Treated	411	200
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	430	213

Reasons for withdrawal

Reasons for withdrawal
Measure	Xilonix Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Overall Study Adverse Event	27	7
Overall Study Death	28	13
Overall Study Lack of Efficacy	299	151
Overall Study Lost to Follow-up	1	1
Overall Study Withdrawal by Subject	38	18
Overall Study Physician Decision	17	10
Overall Study Protocol Terminated	1	0
Overall Study Randomized But Never Treated	19	13

Baseline Characteristics

A Phase III Study of Xilonix in Patients With Advanced Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xilonix n=411 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=200 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).	Total n=611 Participants Total of all reporting groups
Age, Continuous	62.9 years STANDARD_DEVIATION 10.14 • n=5 Participants	61.1 years STANDARD_DEVIATION 9.98 • n=7 Participants	62.3 years STANDARD_DEVIATION 10.11 • n=5 Participants
Sex: Female, Male Female	159 Participants n=5 Participants	94 Participants n=7 Participants	253 Participants n=5 Participants
Sex: Female, Male Male	252 Participants n=5 Participants	106 Participants n=7 Participants	358 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	15 Participants n=5 Participants	2 Participants n=7 Participants	17 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	20 Participants n=5 Participants	8 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	355 Participants n=5 Participants	186 Participants n=7 Participants	541 Participants n=5 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	21 Participants n=5 Participants	4 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Australia	18 Participants n=5 Participants	7 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Austria	12 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment Belgium	49 Participants n=5 Participants	27 Participants n=7 Participants	76 Participants n=5 Participants
Region of Enrollment Czech Republic	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment England	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Hungary	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment Israel	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment Italy	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Region of Enrollment Netherlands	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Poland	30 Participants n=5 Participants	18 Participants n=7 Participants	48 Participants n=5 Participants
Region of Enrollment Spain	118 Participants n=5 Participants	55 Participants n=7 Participants	173 Participants n=5 Participants
Region of Enrollment Switzerland	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment USA	135 Participants n=5 Participants	64 Participants n=7 Participants	199 Participants n=5 Participants
Age (years) < 65 years	229 Participants n=5 Participants	122 Participants n=7 Participants	351 Participants n=5 Participants
Age (years) Between 65 and 75 years	141 Participants n=5 Participants	64 Participants n=7 Participants	205 Participants n=5 Participants
Age (years) > 75 years	41 Participants n=5 Participants	14 Participants n=7 Participants	55 Participants n=5 Participants
Age (years) Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 18 months

Population: The modified intent-to-treat (mITT) population included all participants who were randomized and received at least one infusion of study drug.

Outcome measures

Outcome measures
Measure	Xilonix n=411 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=200 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Overall Survival (OS)	5.6 Months Interval 4.9 to 6.2	5.4 Months Interval 4.6 to 6.2

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: The per protocol (PP) population was defined as participants that had baseline and follow up values for both the DEXA assessment and the European Organization for Research and Treatment of Cancer (EORTC) questionnaire.

Change from baseline in LBM as measured by Dexa scans was reported. DEXA is an X-ray imaging modality used to determine the mass of one material in the presence of another material, using the knowledge of their unique X-ray attenuation at different energies.

Outcome measures

Outcome measures
Measure	Xilonix n=202 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=94 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Change From Baseline in Lean Body Mass (LBM) Measured by Dual-energy X-ray Absorptiometry (DEXA) Scans	0.51 kilogram (kg) Standard Error 0.158	-0.21 kilogram (kg) Standard Error 0.231

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: The PP population was defined as participants that had baseline and follow up values for both the DEXA assessment and the EORTC questionnaire.

The EORTC QLQ-C30 questionnaire incorporates nine multi-item scales: 5 functional scales (physical, cognitive, role, emotional, and social); 3 symptom scales (pain, fatigue, and appetite loss) and a Global Health Status/QoL scale. Each item, except Global Health Status, is answered on a four-point scale (1-4): 1-not at all, 2-a little, 3-quite a bit, 4-very much. Response to Global Health Status is measured on a 1 to 7 scale. "1" being very poor and "7" being excellent. Each scale (symptom scale \[pain, fatigue, and appetite loss\] and Global Health Status/Quality of Life \[QoL\] scale) was linearly transformed to be in range from 0-100 where a higher score represents good health status, while lower scores indicate poor health status. As planned, the data for symptom scales (pain, fatigue, appetite loss) and a Global Health Status/QoL scale was evaluated and reported.

Outcome measures

Outcome measures
Measure	Xilonix n=202 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=94 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Change From Baseline in Symptom Scale and Global Health Status/Quality of Life (QoL) Assessed Through the Cancer-specific European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Qol	-6.64 Units on a scale Standard Error 1.392	-8.16 Units on a scale Standard Error 2.041
Change From Baseline in Symptom Scale and Global Health Status/Quality of Life (QoL) Assessed Through the Cancer-specific European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30) Pain	8.50 Units on a scale Standard Error 1.707	10.27 Units on a scale Standard Error 2.503
Change From Baseline in Symptom Scale and Global Health Status/Quality of Life (QoL) Assessed Through the Cancer-specific European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30) Fatigue	7.42 Units on a scale Standard Error 1.516	8.82 Units on a scale Standard Error 2.223
Change From Baseline in Symptom Scale and Global Health Status/Quality of Life (QoL) Assessed Through the Cancer-specific European Organization for Research and Treatment of Cancer - Quality of Life Questionnaire (EORTC QLQ-C30) Appetite Loss	9.34 Units on a scale Standard Error 2.010	11.84 Units on a scale Standard Error 2.947

SECONDARY outcome

Timeframe: Baseline and Week 8

Population: The PP population was defined as participants that had baseline and follow up values for both the DEXA assessment and the EORTC questionnaire.

Change from baseline in platelet counts up to Week 8 was evaluated.

Outcome measures

Outcome measures
Measure	Xilonix n=202 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=94 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Change From Baseline in Platelet Counts	5.50 1000 cells/cubic millimeter Standard Error 4.721	16.19 1000 cells/cubic millimeter Standard Error 7.082

SECONDARY outcome

Timeframe: Up to 18 Months

Population: The intent-to-treat (ITT) population consisted of all randomized participants.

PFS was defined as time from randomization to tumor progression or death. Progressive Disease defined as increase in tumor burden greater than or equals to (\>=) 25 (%) percent relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented. Participants surviving without disease progression at end of study were censored. PFS was compared by Kaplan-Meier method using log-rank test.

Outcome measures

Outcome measures
Measure	Xilonix n=430 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=213 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Progression Free Survival (PFS)	2.1 Months Interval 2.1 to 2.1	2.1 Months Interval 2.0 to 2.1

SECONDARY outcome

Timeframe: Up to 18 months

Population: The mITT population included all participants who were randomized and received at least one infusion of study drug.

The percentage of OR was estimated by dividing the total number of confirmed complete response (CR) and partial response (PR) by the total number of participants randomized where CR was complete disappearance of all lesions (whether measurable or not, and no new lesions); confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented and PR was decrease in tumor burden \>= 50 % relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation.

Outcome measures

Outcome measures
Measure	Xilonix n=411 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=200 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Percentage of Participants With Objective Response (OR)	0 Percentage of Participants	0 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 18 months

Population: The participants with baseline and follow up radiographic assessments were included in this analysis.

Percentage of participants who achieved disease control was estimated by dividing the total number of confirmed CRs, PRs and stable disease (SD) by the total number of participants randomized where CR was complete disappearance of all lesions (whether measurable or not, and no new lesions); confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented, PR was decrease in tumor burden \>= 50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation and SD defined as not meeting criteria for CR and PR, in absence of Progressive Disease (increase in tumor burden \>= 25 % relative to nadir (minimum recorded tumor burden) confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented).

Outcome measures

Outcome measures
Measure	Xilonix n=296 Participants Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=154 Participants Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Percentage of Participants With Disease Control	25 Percentage of Participants	27.3 Percentage of Participants

Adverse Events

Xilonix

Serious events: 169 serious events

Other events: 324 other events

Deaths: 28 deaths

Placebo

Serious events: 84 serious events

Other events: 167 other events

Deaths: 13 deaths

Serious adverse events

Other adverse events

Additional Information

Product Development Portfolio Leader

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Measure	Xilonix n=411 participants at risk Participants received 7.5 milligram per kilogram (mg/kg) Xilonix (MABp1) via intravenous (IV) injection once every 2 weeks until evidence of radiographic or clinical progression along with best supportive care (BSC) (up to 18 months).	Placebo n=200 participants at risk Participants received placebo via IV injection once every 2 weeks until evidence of radiographic or clinical progression plus BSC (up to 18 months).
Psychiatric disorders Insomnia	3.9% 16/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	5.0% 10/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Renal and urinary disorders Proteinuria	2.7% 11/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	5.5% 11/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	9.7% 40/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	13.5% 27/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	10.2% 42/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	10.0% 20/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Cardiac disorders Sinus Tachycardia	2.7% 11/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	5.0% 10/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal Pain	19.0% 78/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	20.5% 41/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	12.4% 51/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	15.5% 31/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	10.9% 45/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	11.0% 22/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	19.2% 79/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	23.0% 46/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	11.2% 46/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	10.0% 20/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
General disorders Asthenia	15.3% 63/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	17.5% 35/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
General disorders Fatigue	26.5% 109/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	30.0% 60/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
General disorders Oedema Peripheral	9.5% 39/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	11.5% 23/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
General disorders Pyrexia	9.2% 38/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	13.5% 27/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Investigations Aspartate Aminotransferase Increased	5.6% 23/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	3.0% 6/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Investigations Blood Alkaline Phosphatase Increased	4.9% 20/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	6.5% 13/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Investigations Blood Bilirubin Increased	6.1% 25/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	3.5% 7/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased Appetite	20.4% 84/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	25.5% 51/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back Pain	10.7% 44/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	13.5% 27/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Nervous system disorders Headache	5.1% 21/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	6.5% 13/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.9% 49/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	13.5% 27/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.
Vascular disorders Hypertension	6.1% 25/411 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.	7.5% 15/200 • Up to 18 months Safety analysis included the safety population, defined as enrolled participants who received at least one dose of study drug.