Morphotek Investigation in Colorectal Cancer: Research of MORAb-004 (MICRO)

• Sponsor: Morphotek (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01507545
• Collaborator: (none)
• Enrollment: 154
• Locations: 67
• Arms: 2
• Actual Duration (Months): 18.8
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether therapy with MORAb-004 is effective and safe in the treatment of metastatic, colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer; Colorectal Cancer	Drug: MORAb-004; Drug: Placebo; Other: Best supportive care	Phase 2

Detailed Description

Tumor endothelial marker-1 also referred to as TEM-1 is expressed in the supportive tissue, as well as, on the cells within the tumor. TEM-1, which is a cell surface glycoprotein, and is expressed in the stromal compartment (cells) of nearly all human tumors. In preclinical studies, it has been shown that TEM-1 plays a key role in tumor growth and the vascularization of tumors. There is evidence suggesting an association between the level of TEM-1, 7, 7R, 8 in relation to lymph node involvement and disease progression. MORAb-004 is a humanized immunoglobulin G (IgG1/κ) antibody directed against endosialin/TEM-1. Nonclinical pharmacological studies showed that MORAb-004 has the ability to block specific TEM-1 receptor-ligand interactions. Immunohistochemistry studies of human tumor biopsy samples demonstrate TEM-1 expression and MORAb-004 binding to tumor stromal cells, in particular mural cell compartment of neovessels and cancer-associated fibroblasts. All of which suggests a potential effective treatment. Researchers hypothesize that an antibody therapy that binds to TEM-1 may be efficacious in the treatment of metastatic, colorectal cancer. This clinical study is a proof of concept study to see if an anti-TEM-1 agent is safe and effective in the treatment of metastatic, colorectal cancer.

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-controlled Study of the Efficacy & Safety of Monotherapy MORAb-004 Plus Best Supportive Care in Subjects With Chemorefractory Metastatic Colorectal Cancer
• Actual Study Start Date: Mar 27, 2012
• Actual Primary Completion Date: Oct 20, 2013
• Actual Study Completion Date: Oct 20, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: MORAb-004	Drug: MORAb-004; MORAb-004 8mg per kg IV once a week; Other: Best supportive care; Best supportive care to improve quality of life
Placebo Comparator: Placebo	Drug: Placebo; Placebo - normal saline IV once a week; Other: Best supportive care; Best supportive care to improve quality of life

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From the date of randomization to the date of the first observation of PD or death due to any cause (up to approximately 1 year 7 months)]

   PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression (PD) or death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further antitumor treatment. PFS was summarized for each treatment group using Kaplan-Meier estimation curves.

Secondary Outcome Measures

1. Overall Survival (OS) [From the date of randomization to the date of death due to any cause (up to approximately 1 year 7 months)]

   OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause. OS was summarized for each treatment group using Kaplan-Meier estimation curves. In the absence of death confirmation or for participants alive at the time of analysis, the survival time was censored at the last date known to be alive.

2. Overall Response Rate (ORR) [From the date of randomization to the first documentation of CR or PR (up to approximately 1 year 7 months)]

   ORR was defined as the percentage of subjects achieving either CR or PR using RECIST v.1.1. CR was 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 less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

3. Time to Tumor Response (TTR) [From the date of randomization to first documentation of objective tumor response (CR or PR) (up to approximately 1 year 7 months)]

   Time to tumor response was defined for those participants with objective evidence of confirmed CR or PR as the time from randomization to first documentation of objective tumor response (CR or PR). CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

4. Duration of Response (DOR) [From the date of first objective response (CR or PR) to objective tumor progression or death regardless of cause (up to approximately 1 year 7 months)]

   The DOR was defined as the time from first documentation of objective response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

5. Biomarkers Based PFS, Within Treatment Group [From the date of randomization up to approximately 1 year 7 months]

   The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for PFS was not carried out.

6. Biomarkers Based OS, Within Treatment Group [From the date of randomization up to approximately 1 year 7 months]

   The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for OS was not carried out.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females >18 years old

• Diagnosis of metastatic, colorectal cancer

• Significant medical conditions must be well-controlled and stable for at least 30 days prior to the first treatment infusion

• Be willing and able to provide written informed consent

Exclusion Criteria:

• No prior treatment for metastatic colorectal cancer

• Other serious systemic diseases (bacterial or fungal)

• Clinically significant heart disease or an arrhythmia on an ECG within the past 6 months

• Known allergic reaction to monoclonal antibody therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Hem/Onc Medical Group, Inc.	Alhambra	California	United States	91801
2	Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
3	Providence St. Joseph Medical Center-Disney Family Cancer Center	Burbank	California	United States	91505
4	St. Jude Heritage Healthcare	Fullerton	California	United States	92835
5	The Thomas and Dorothy Leavey Cancer Center Northridge Hospital Medical Center	Northridge	California	United States	91328
6	UC Davis Comprehensive Cancer Center	Sacramento	California	United States
7	Sharp Memorial Hospital	San Diego	California	United States	92123
8	CPMCRI / Pacific Hematology Oncology Associates	San Francisco	California	United States	94115
9	Central Coast Medical Oncology	Santa Maria	California	United States	93454
10	UCLA Hematology Oncology	Santa Monica	California	United States	90404
11	Colorado Cancer Research Program	Denver	Colorado	United States	80224
12	St. Mary's Hospital Regional Cancer Center	Grand Junction	Colorado	United States	81501
13	Lutheran Hematology & Oncology	Wheat Ridge	Colorado	United States	80033
14	Christiana Care Health Services	Newark	Delaware	United States	19713
15	Georgetown University	Washington	District of Columbia	United States	20007
16	Mayo Clinic Florida Hematology/Oncology	Jacksonville	Florida	United States	32224
17	Integrated Community Oncology Network / Cancer Specialists of North Florida	Jacksonville	Florida	United States	32256
18	Compass Research, LLC	Orange City	Florida	United States	32763
19	Hematology Oncology Associates of the Treasure Coast	Port Saint Lucie	Florida	United States	34952
20	Cancer Care Centers of Brevard	Rockledge	Florida	United States	32955
21	H. Lee Moffitt Cancer Center (Moffitt Cancer Center)	Tampa	Florida	United States	33612
22	Suburban Hematology-Oncology Associates, P.C.	Duluth	Georgia	United States	30096
23	Suburban Hematology-Oncology Assoc., PC	Lawrenceville	Georgia	United States	30046
24	Suburban Hematology-Oncology Associates, P.C.	Snellville	Georgia	United States	30078
25	Medical and Surgical Specialists	Galesburg	Illinois	United States	61401
26	Ingalls Cancer Research Center	Harvey	Illinois	United States	60426
27	Oncology Specialists,S.C. Center for Advanced Care	Park Ridge	Illinois	United States	60068
28	Illinois CancerCare, P.C.	Peoria	Illinois	United States	61615
29	Carle Cancer Center	Urbana	Illinois	United States	61801
30	Medical Oncology & Hematology Associates (Clinic #3)	Clive	Iowa	United States	50325
31	Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
32	Medical Oncology & Hematology Associates (Clinic #1)	Des Moines	Iowa	United States	50309
33	Medical Oncology & Hematology Associates (Clinic #2)	Des Moines	Iowa	United States	50314
34	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
35	Cancer Center of Kansas	Wichita	Kansas	United States	67208
36	Cancer Center of Kansas	Wichita	Kansas	United States	67214
37	Central Baptist Hospital	Lexington	Kentucky	United States	40503
38	John Hopkins University	Baltimore	Maryland	United States	21231-1000
39	Weinberg Cancer Institute at Franklin Square	Baltimore	Maryland	United States	21237
40	Lahey Clinic	Burlington	Massachusetts	United States	01805
41	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
42	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
43	Henry Ford Health System	Detroit	Michigan	United States	48202
44	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
45	Essentia Health Duluth CCOP	Duluth	Minnesota	United States	55805
46	Mayo Clinic	Rochester	Minnesota	United States	55905
47	Coborn Cancer Center/ CentraCare Health Plaza	Saint Cloud	Minnesota	United States	56303
48	Metro Minnesota CCOP	Saint Louis Park	Minnesota	United States	55416
49	Regions Hospital	Saint Louis Park	Minnesota	United States	55416
50	St. John's Hospital	Saint Louis Park	Minnesota	United States	55416
51	CCCN	Las Vegas	Nevada	United States	89169
52	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
53	Mount Sinai Medical Center	New York	New York	United States	10029
54	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
55	Presbyterian Hospital Cancer Center	Charlotte	North Carolina	United States	28204
56	Duke University Medical Center	Durham	North Carolina	United States	27710
57	Piedmont Hematology Oncology Associates PA	Winston-Salem	North Carolina	United States	27103
58	Medcenter One	Bismarck	North Dakota	United States	58501
59	TriHealth Oncology Institute/Oncology Partners Network	Cincinnati	Ohio	United States	45247
60	Hickman Cancer Center at Flower Hospital	Sylvania	Ohio	United States	43560
61	Mercy Cancer Center	Toledo	Ohio	United States	43623
62	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
63	Pharma Resource	East Providence	Rhode Island	United States	02915
64	Rhode Island Hospital	Providence	Rhode Island	United States	02903
65	The Miriam Hospital	Providence	Rhode Island	United States	02906
66	St. Vincent Hospital / Green Bay Oncology	Green Bay	Wisconsin	United States	54301
67	St. Mary's Hospital / Green Bay Oncology	Green Bay	Wisconsin	United States	54303

Sponsors and Collaborators

• Morphotek

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Morphotek
• ClinicalTrials.gov Identifier: NCT01507545
• Other Study ID Numbers: MORAb-004-202-CRC
• First Posted: Jan 11, 2012
• Last Update Posted: May 6, 2022
• Last Verified: Sep 1, 2015

• Keywords provided by Morphotek: mCRC; chemorefractory metastatic colorectal cancer
• Additional relevant MeSH terms: Colorectal Neoplasms

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 61 investigative sites in the United States from 27 March 2012 to 20 October 2013.
Pre-assignment Detail	A total of 154 participants were screened and enrolled (signed informed consent form), of which 28 were screen failures, 126 were randomized and 122 were treated. Study was terminated by the sponsor at the end of Stage 1 due to futility, hence Stage 2 was not carried out.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 milligram per kilogram (mg/kg), infusion intravenously (IV), once weekly, in each 2-week treatment cycle along with the best supportive care (BSC) which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Period Title: Overall Study
STARTED	84	42
Treated/Safety Set	82	40
COMPLETED	0	0
NOT COMPLETED	84	42

Baseline Characteristics

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC	Total
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Total of all reporting groups
Overall Participants	84	42	126
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (11.72)	61.8 (10.61)	61.5 (11.32)
Sex: Female, Male (Count of Participants)
Female	43 51.2%	16 38.1%	59 46.8%
Male	41 48.8%	26 61.9%	67 53.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 7.1%	1 2.4%	7 5.6%
Not Hispanic or Latino	75 89.3%	40 95.2%	115 91.3%
Unknown or Not Reported	3 3.6%	1 2.4%	4 3.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.2%	1 2.4%	2 1.6%
Asian	4 4.8%	2 4.8%	6 4.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 3.6%	3 7.1%	6 4.8%
White	74 88.1%	36 85.7%	110 87.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 2.4%	0 0%	2 1.6%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression (PD) or death due to any cause. PD was defined as at least a 20 percent (%) increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of last tumor assessment without evidence of progression prior to the date of initiation of further antitumor treatment. PFS was summarized for each treatment group using Kaplan-Meier estimation curves.
Time Frame	From the date of randomization to the date of the first observation of PD or death due to any cause (up to approximately 1 year 7 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, analyzed according to the treatment assigned by the IVRS/IWRS.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	84	42
Median (95% Confidence Interval) [weeks]	8.1	8.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MORAb-004 8.0 mg/kg + BSC, Placebo + BSC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7335
	Comments
	Method	One-sided log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause. OS was summarized for each treatment group using Kaplan-Meier estimation curves. In the absence of death confirmation or for participants alive at the time of analysis, the survival time was censored at the last date known to be alive.
Time Frame	From the date of randomization to the date of death due to any cause (up to approximately 1 year 7 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, analyzed according to the treatment assigned by IVRS/IWRS.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	84	42
Median (95% Confidence Interval) [months]	4.8	6.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MORAb-004 8.0 mg/kg + BSC, Placebo + BSC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9498
	Comments
	Method	One-sided log-rank test
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.93 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was defined as the percentage of subjects achieving either CR or PR using RECIST v.1.1. CR was 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 less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	From the date of randomization to the first documentation of CR or PR (up to approximately 1 year 7 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, analyzed according to the treatment assigned by IVRS/IWRS.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	84	42
Number (95% Confidence Interval) [percentage of participants]	0 0%	2.4 5.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MORAb-004 8.0 mg/kg + BSC, Placebo + BSC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.333
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference of arms
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -6.992 to 2.230
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to Tumor Response (TTR)
Description	Time to tumor response was defined for those participants with objective evidence of confirmed CR or PR as the time from randomization to first documentation of objective tumor response (CR or PR). CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	From the date of randomization to first documentation of objective tumor response (CR or PR) (up to approximately 1 year 7 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, analyzed according to the treatment assigned by the IVRS/IWRS. Here overall number analyzed "N" are the participants who had achieved CR or PR.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	0	1
Median (Full Range) [weeks]	NA

5. Secondary Outcome

Title	Duration of Response (DOR)
Description	The DOR was defined as the time from first documentation of objective response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. CR was 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 was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame	From the date of first objective response (CR or PR) to objective tumor progression or death regardless of cause (up to approximately 1 year 7 months)

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, analyzed according to the treatment assigned by the IVRS/IWRS. Here overall number analyzed "N" are the participants who had achieved CR or PR.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	0	1
Median (Full Range) [weeks]	NA

6. Secondary Outcome

Title	Biomarkers Based PFS, Within Treatment Group
Description	The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for PFS was not carried out.
Time Frame	From the date of randomization up to approximately 1 year 7 months

Outcome Measure Data

Analysis Population Description

The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for PFS was not carried out.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	0	0

7. Secondary Outcome

Title	Biomarkers Based OS, Within Treatment Group
Description	The statistical evidence to support the use of the biomarker identified in Stage 1 interim analysis for Stage 2 selection of participants as designed was not adequate to clearly define a biomarker responsive population. The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for OS was not carried out.
Time Frame	From the date of randomization up to approximately 1 year 7 months

Outcome Measure Data

Analysis Population Description

The study was terminated by the sponsor at the end of Stage 1 and enrollment of stage 2 did not occur due to futility, hence Stage 2 and biomarker based analysis for OS was not carried out.

Arm/Group Title	MORAb-004 8.0 mg/kg + BSC	Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).	Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
Measure Participants	0	0

Adverse Events

Time Frame	From the date of randomization of the study drug up to 45 days after the last infusion of study drug (approximately up to 1 year 7 months)
Arm/Group Title	MORAb-004 8.0 mg/kg + BSC		Placebo + BSC
Arm/Group Description	Participants received MORAb-004 8 mg/kg, infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).		Participants received MORAb-004 matching placebo infusion IV, once weekly, in each 2-week treatment cycle along with the BSC which included those measures intended to provide palliation of all symptoms and improve quality of life, until disease progression or discontinuation from any reason (up to Cycle 24).
All Cause Mortality
	MORAb-004 8.0 mg/kg + BSC		Placebo + BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/82 (15.9%)		4/40 (10%)
Serious Adverse Events
	MORAb-004 8.0 mg/kg + BSC		Placebo + BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/82 (37.8%)		15/40 (37.5%)
Blood and lymphatic system disorders
Anaemia	1/82 (1.2%)		1/40 (2.5%)
Neutropenia	1/82 (1.2%)		0/40 (0%)
Gastrointestinal disorders
Abdominal Pain	3/82 (3.7%)		0/40 (0%)
Small Intestinal Obstruction	3/82 (3.7%)		0/40 (0%)
Ascites	1/82 (1.2%)		0/40 (0%)
Caecitis	1/82 (1.2%)		0/40 (0%)
Constipation	1/82 (1.2%)		1/40 (2.5%)
Intestinal Obstruction	1/82 (1.2%)		1/40 (2.5%)
Diarrhoea	0/82 (0%)		1/40 (2.5%)
Rectal Haemorrhage	0/82 (0%)		1/40 (2.5%)
General disorders
Pyrexia	2/82 (2.4%)		2/40 (5%)
Asthenia	1/82 (1.2%)		0/40 (0%)
Fatigue	1/82 (1.2%)		0/40 (0%)
Gait Disturbance	1/82 (1.2%)		0/40 (0%)
General Physical Health Deterioration	1/82 (1.2%)		0/40 (0%)
Hepatobiliary disorders
Hepatic Failure	3/82 (3.7%)		0/40 (0%)
Infections and infestations
Abdominal Wall Abscess	1/82 (1.2%)		0/40 (0%)
Intestinal Fistula Infection	1/82 (1.2%)		0/40 (0%)
Pneumonia	1/82 (1.2%)		1/40 (2.5%)
Septic Shock	0/82 (0%)		1/40 (2.5%)
Injury, poisoning and procedural complications
Infusion Related Reaction	1/82 (1.2%)		0/40 (0%)
Metabolism and nutrition disorders
Dehydration	5/82 (6.1%)		2/40 (5%)
Diabetes Mellitus Inadequate Control	1/82 (1.2%)		0/40 (0%)
Hypocalcaemia	1/82 (1.2%)		0/40 (0%)
Hypokalaemia	1/82 (1.2%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	4/82 (4.9%)		0/40 (0%)
Muscular Weakness	2/82 (2.4%)		0/40 (0%)
Bone Pain	0/82 (0%)		1/40 (2.5%)
Muscle Spasms	0/82 (0%)		1/40 (2.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm Malignant	7/82 (8.5%)		2/40 (5%)
Metastases To Central Nervous System	1/82 (1.2%)		0/40 (0%)
Nervous system disorders
Hypoaesthesia	1/82 (1.2%)		0/40 (0%)
Cauda Equina Syndrome	0/82 (0%)		1/40 (2.5%)
Headache	0/82 (0%)		1/40 (2.5%)
Presyncope	0/82 (0%)		1/40 (2.5%)
Psychiatric disorders
Confusional State	1/82 (1.2%)		0/40 (0%)
Renal and urinary disorders
Renal Failure Acute	2/82 (2.4%)		1/40 (2.5%)
Renal Failure	0/82 (0%)		1/40 (2.5%)
Urinary Tract Obstruction	0/82 (0%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/82 (2.4%)		0/40 (0%)
Respiratory Failure	1/82 (1.2%)		0/40 (0%)
Pleural Effusion	0/82 (0%)		1/40 (2.5%)
Vascular disorders
Deep Vein Thrombosis	2/82 (2.4%)		1/40 (2.5%)
Embolism	2/82 (2.4%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	MORAb-004 8.0 mg/kg + BSC		Placebo + BSC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/82 (93.9%)		40/40 (100%)
Blood and lymphatic system disorders
Anaemia	10/82 (12.2%)		5/40 (12.5%)
Lymphopenia	6/82 (7.3%)		0/40 (0%)
Thrombocytopenia	0/82 (0%)		1/40 (2.5%)
Cardiac disorders
Sinus Tachycardia	4/82 (4.9%)		0/40 (0%)
Atrial Fibrillation	1/82 (1.2%)		0/40 (0%)
Bradycardia	1/82 (1.2%)		0/40 (0%)
Cardiac Failure Congestive	1/82 (1.2%)		0/40 (0%)
Cardiomyopathy	1/82 (1.2%)		0/40 (0%)
Palpitations	1/82 (1.2%)		0/40 (0%)
Sinus Bradycardia	1/82 (1.2%)		1/40 (2.5%)
Tachycardia	1/82 (1.2%)		0/40 (0%)
Sinus Arrhythmia	0/82 (0%)		1/40 (2.5%)
Ear and labyrinth disorders
Ear Pain	1/82 (1.2%)		0/40 (0%)
Eye disorders
Eye Pain	1/82 (1.2%)		0/40 (0%)
Vision Blurred	1/82 (1.2%)		0/40 (0%)
Conjunctivitis	0/82 (0%)		1/40 (2.5%)
Eyelid Disorder	0/82 (0%)		1/40 (2.5%)
Vitreous Floaters	0/82 (0%)		1/40 (2.5%)
Gastrointestinal disorders
Nausea	32/82 (39%)		14/40 (35%)
Constipation	22/82 (26.8%)		13/40 (32.5%)
Abdominal Pain	16/82 (19.5%)		8/40 (20%)
Vomiting	17/82 (20.7%)		9/40 (22.5%)
Diarrhoea	16/82 (19.5%)		6/40 (15%)
Abdominal Distension	8/82 (9.8%)		1/40 (2.5%)
Abdominal Pain Upper	6/82 (7.3%)		2/40 (5%)
Ascites	5/82 (6.1%)		2/40 (5%)
Abdominal Pain Lower	4/82 (4.9%)		2/40 (5%)
Dyspepsia	3/82 (3.7%)		0/40 (0%)
Dysphagia	3/82 (3.7%)		0/40 (0%)
Gastrooesophageal Reflux Disease	3/82 (3.7%)		2/40 (5%)
Abdominal Discomfort	2/82 (2.4%)		0/40 (0%)
Dry Mouth	2/82 (2.4%)		1/40 (2.5%)
Stomatitis	2/82 (2.4%)		2/40 (5%)
Colitis	1/82 (1.2%)		0/40 (0%)
Faecal Volume Increased	1/82 (1.2%)		0/40 (0%)
Flatulence	1/82 (1.2%)		1/40 (2.5%)
Haematochezia	1/82 (1.2%)		0/40 (0%)
Lip Haematoma	1/82 (1.2%)		0/40 (0%)
Paraesthesia Oral	1/82 (1.2%)		0/40 (0%)
Proctalgia	1/82 (1.2%)		2/40 (5%)
Rectal Haemorrhage	1/82 (1.2%)		1/40 (2.5%)
Toothache	1/82 (1.2%)		0/40 (0%)
Eructation	0/82 (0%)		1/40 (2.5%)
Gingival Pain	0/82 (0%)		1/40 (2.5%)
Perianal Erythema	0/82 (0%)		1/40 (2.5%)
General disorders
Fatigue	43/82 (52.4%)		19/40 (47.5%)
Oedema Peripheral	12/82 (14.6%)		6/40 (15%)
Pyrexia	11/82 (13.4%)		5/40 (12.5%)
Asthenia	8/82 (9.8%)		4/40 (10%)
Chills	8/82 (9.8%)		4/40 (10%)
Pain	7/82 (8.5%)		0/40 (0%)
Malaise	4/82 (4.9%)		0/40 (0%)
Gait Disturbance	3/82 (3.7%)		0/40 (0%)
Influenza Like Illness	2/82 (2.4%)		1/40 (2.5%)
Non-Cardiac Chest Pain	2/82 (2.4%)		0/40 (0%)
Early Satiety	1/82 (1.2%)		0/40 (0%)
Injection Site Reaction	1/82 (1.2%)		0/40 (0%)
Chest Discomfort	0/82 (0%)		1/40 (2.5%)
Suprapubic Pain	0/82 (0%)		1/40 (2.5%)
Hepatobiliary disorders
Jaundice	2/82 (2.4%)		0/40 (0%)
Hyperbilirubinaemia	1/82 (1.2%)		2/40 (5%)
Immune system disorders
Drug Hypersensitivity	1/82 (1.2%)		0/40 (0%)
Infections and infestations
Urinary Tract Infection	4/82 (4.9%)		8/40 (20%)
Upper Respiratory Tract Infection	2/82 (2.4%)		1/40 (2.5%)
Abdominal Infection	1/82 (1.2%)		0/40 (0%)
Bronchitis	1/82 (1.2%)		0/40 (0%)
Gastroenteritis Viral	1/82 (1.2%)		0/40 (0%)
Nasopharyngitis	1/82 (1.2%)		0/40 (0%)
Cystitis	0/82 (0%)		1/40 (2.5%)
Diarrhoea Infectious	0/82 (0%)		1/40 (2.5%)
Oral Candidiasis	0/82 (0%)		2/40 (5%)
Oral Herpes	0/82 (0%)		1/40 (2.5%)
Injury, poisoning and procedural complications
Infusion Related Reaction	1/82 (1.2%)		0/40 (0%)
Contusion	1/82 (1.2%)		0/40 (0%)
Fall	1/82 (1.2%)		0/40 (0%)
Post Procedural Haemorrhage	1/82 (1.2%)		0/40 (0%)
Compression Fracture	0/82 (0%)		1/40 (2.5%)
Investigations
Blood Alkaline Phosphatase Increased	10/82 (12.2%)		1/40 (2.5%)
Weight Decreased	10/82 (12.2%)		3/40 (7.5%)
Aspartate Aminotransferase Increased	6/82 (7.3%)		1/40 (2.5%)
Alanine Aminotransferase Increased	5/82 (6.1%)		0/40 (0%)
Blood Lactate Dehydrogenase Increased	5/82 (6.1%)		4/40 (10%)
Blood Bilirubin Increased	3/82 (3.7%)		0/40 (0%)
Blood Creatinine Increased	3/82 (3.7%)		0/40 (0%)
Electrocardiogram Abnormal	3/82 (3.7%)		1/40 (2.5%)
Activated Partial Thromboplastin Time Prolonged	2/82 (2.4%)		2/40 (5%)
Blood Cholesterol Increased	1/82 (1.2%)		0/40 (0%)
Blood Magnesium Increased	1/82 (1.2%)		0/40 (0%)
Blood Pressure Decreased	1/82 (1.2%)		0/40 (0%)
Blood Uric Acid Increased	1/82 (1.2%)		1/40 (2.5%)
Cardiac Murmur	1/82 (1.2%)		0/40 (0%)
Ejection Fraction Decreased	1/82 (1.2%)		0/40 (0%)
International Normalised Ratio Increased	1/82 (1.2%)		0/40 (0%)
Lymphocyte Count Decreased	1/82 (1.2%)		0/40 (0%)
Platelet Count Decreased	1/82 (1.2%)		0/40 (0%)
Prothrombin Time Prolonged	1/82 (1.2%)		0/40 (0%)
White Blood Cell Count Decreased	1/82 (1.2%)		0/40 (0%)
Blood Glucose Increased	0/82 (0%)		1/40 (2.5%)
Electrocardiogram ST Segment Depression	0/82 (0%)		1/40 (2.5%)
Haemoglobin Decreased	0/82 (0%)		1/40 (2.5%)
Peritoneal Fluid Analysis Abnormal	0/82 (0%)		1/40 (2.5%)
Peritoneal Fluid Analysis Normal	0/82 (0%)		1/40 (2.5%)
Transaminases Increased	0/82 (0%)		1/40 (2.5%)
Metabolism and nutrition disorders
Decreased Appetite	28/82 (34.1%)		11/40 (27.5%)
Dehydration	7/82 (8.5%)		3/40 (7.5%)
Hyponatraemia	7/82 (8.5%)		0/40 (0%)
Hypokalaemia	4/82 (4.9%)		2/40 (5%)
Hypoalbuminaemia	3/82 (3.7%)		0/40 (0%)
Hypocalcaemia	2/82 (2.4%)		1/40 (2.5%)
Hypomagnesaemia	3/82 (3.7%)		1/40 (2.5%)
Hyperglycaemia	2/82 (2.4%)		1/40 (2.5%)
Failure To Thrive	1/82 (1.2%)		0/40 (0%)
Hypoglycaemia	1/82 (1.2%)		0/40 (0%)
Hypophosphataemia	1/82 (1.2%)		0/40 (0%)
Hypovolaemia	1/82 (1.2%)		0/40 (0%)
Increased Appetite	1/82 (1.2%)		0/40 (0%)
Hypophagia	0/82 (0%)		1/40 (2.5%)
Musculoskeletal and connective tissue disorders
Back Pain	15/82 (18.3%)		2/40 (5%)
Musculoskeletal Pain	9/82 (11%)		1/40 (2.5%)
Musculoskeletal Chest Pain	7/82 (8.5%)		2/40 (5%)
Arthralgia	6/82 (7.3%)		1/40 (2.5%)
Pain In Extremity	6/82 (7.3%)		2/40 (5%)
Myalgia	4/82 (4.9%)		2/40 (5%)
Muscular Weakness	1/82 (1.2%)		2/40 (5%)
Bone Pain	1/82 (1.2%)		0/40 (0%)
Flank Pain	1/82 (1.2%)		2/40 (5%)
Groin Pain	1/82 (1.2%)		0/40 (0%)
Muscle Spasms	1/82 (1.2%)		2/40 (5%)
Neck Pain	1/82 (1.2%)		0/40 (0%)
Pain In Jaw	1/82 (1.2%)		0/40 (0%)
Musculoskeletal Discomfort	0/82 (0%)		2/40 (5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain	2/82 (2.4%)		0/40 (0%)
Tumour Pain	1/82 (1.2%)		0/40 (0%)
Nervous system disorders
Headache	16/82 (19.5%)		8/40 (20%)
Dizziness	6/82 (7.3%)		0/40 (0%)
Neuropathy Peripheral	3/82 (3.7%)		3/40 (7.5%)
Dysgeusia	2/82 (2.4%)		1/40 (2.5%)
Hypoaesthesia	1/82 (1.2%)		1/40 (2.5%)
Paraesthesia	2/82 (2.4%)		1/40 (2.5%)
Peripheral Sensory Neuropathy	2/82 (2.4%)		0/40 (0%)
Brain Oedema	1/82 (1.2%)		0/40 (0%)
Convulsion	1/82 (1.2%)		0/40 (0%)
Hypogeusia	1/82 (1.2%)		0/40 (0%)
Lethargy	1/82 (1.2%)		1/40 (2.5%)
Memory Impairment	1/82 (1.2%)		0/40 (0%)
Peroneal Nerve Palsy	1/82 (1.2%)		0/40 (0%)
Restless Legs Syndrome	1/82 (1.2%)		1/40 (2.5%)
Sinus Headache	1/82 (1.2%)		0/40 (0%)
Slow Speech	1/82 (1.2%)		0/40 (0%)
Balance Disorder	0/82 (0%)		1/40 (2.5%)
Psychiatric disorders
Insomnia	8/82 (9.8%)		3/40 (7.5%)
Anxiety	5/82 (6.1%)		2/40 (5%)
Depression	3/82 (3.7%)		2/40 (5%)
Libido Decreased	1/82 (1.2%)		0/40 (0%)
Renal and urinary disorders
Proteinuria	5/82 (6.1%)		1/40 (2.5%)
Renal Failure Acute	1/82 (1.2%)		0/40 (0%)
Dysuria	2/82 (2.4%)		0/40 (0%)
Pollakiuria	2/82 (2.4%)		0/40 (0%)
Renal Failure	1/82 (1.2%)		0/40 (0%)
Urinary Incontinence	2/82 (2.4%)		2/40 (5%)
Chromaturia	1/82 (1.2%)		0/40 (0%)
Micturition Urgency	1/82 (1.2%)		0/40 (0%)
Ureteric Stenosis	1/82 (1.2%)		0/40 (0%)
Urinary Tract Pain	1/82 (1.2%)		1/40 (2.5%)
Urine Flow Decreased	1/82 (1.2%)		0/40 (0%)
Haematuria	0/82 (0%)		1/40 (2.5%)
Incontinence	0/82 (0%)		1/40 (2.5%)
Nephrolithiasis 0	0/82 (0%)		1/40 (2.5%)
Reproductive system and breast disorders
Pelvic Pain	1/82 (1.2%)		1/40 (2.5%)
Perineal Pain	1/82 (1.2%)		0/40 (0%)
Scrotal Swelling	1/82 (1.2%)		0/40 (0%)
Scrotal Pain	0/82 (0%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	20/82 (24.4%)		9/40 (22.5%)
Cough	12/82 (14.6%)		9/40 (22.5%)
Dyspnoea Exertional	3/82 (3.7%)		1/40 (2.5%)
Oropharyngeal Pain	3/82 (3.7%)		2/40 (5%)
Dysphonia	2/82 (2.4%)		1/40 (2.5%)
Epistaxis	2/82 (2.4%)		1/40 (2.5%)
Productive Cough	2/82 (2.4%)		0/40 (0%)
Rhinorrhoea	2/82 (2.4%)		0/40 (0%)
Upper-Airway Cough Syndrome	2/82 (2.4%)		1/40 (2.5%)
Chronic Obstructive Pulmonary Disease	1/82 (1.2%)		0/40 (0%)
Haemoptysis	1/82 (1.2%)		0/40 (0%)
Hypoxia	1/82 (1.2%)		0/40 (0%)
Nasal Congestion	1/82 (1.2%)		0/40 (0%)
Pleural Effusion	1/82 (1.2%)		1/40 (2.5%)
Pulmonary Congestion	1/82 (1.2%)		0/40 (0%)
Wheezing	1/82 (1.2%)		1/40 (2.5%)
Pneumonitis	0/82 (0%)		1/40 (2.5%)
Pulmonary Embolism	0/82 (0%)		1/40 (2.5%)
Skin and subcutaneous tissue disorders
Pruritus	8/82 (9.8%)		1/40 (2.5%)
Rash	5/82 (6.1%)		1/40 (2.5%)
Night Sweats	4/82 (4.9%)		1/40 (2.5%)
Hyperhidrosis	3/82 (3.7%)		4/40 (10%)
Alopecia	1/82 (1.2%)		2/40 (5%)
Dermatitis Atopic	1/82 (1.2%)		0/40 (0%)
Erythema	1/82 (1.2%)		0/40 (0%)
Exfoliative Rash	1/82 (1.2%)		0/40 (0%)
Pain Of Skin	1/82 (1.2%)		0/40 (0%)
Petechiae	1/82 (1.2%)		0/40 (0%)
Pruritus Generalised	1/82 (1.2%)		0/40 (0%)
Rash Erythematous	1/82 (1.2%)		0/40 (0%)
Rash Maculo-Papular	1/82 (1.2%)		0/40 (0%)
Dermatitis	0/82 (0%)		1/40 (2.5%)
Dermatitis Acneiform	0/82 (0%)		1/40 (2.5%)
Vascular disorders
Flushing	6/82 (7.3%)		3/40 (7.5%)
Hypertension	5/82 (6.1%)		1/40 (2.5%)
Deep Vein Thrombosis	1/82 (1.2%)		0/40 (0%)
Hypotension	3/82 (3.7%)		0/40 (0%)
Hot Flush	2/82 (2.4%)		2/40 (5%)
Haematoma	1/82 (1.2%)		0/40 (0%)

Limitations/Caveats

The study was terminated by the sponsor at the end of Stage 1 due to futility, hence Stage 2 was not carried out.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.