Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer

• Sponsor: Sanofi (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02984683
• Collaborator: (none)
• Enrollment: 23
• Locations: 13
• Arms: 2
• Actual Duration (Months): 17.5
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Primary Objective:

To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Part 1: To select the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658. Part 2: Part 2a: To demonstrate the activity of SAR566658 based on ORR in participants overexpressing CA6 (membrane intensity of 2+, 3+ in greater than or equal to (>=) 30% of tumor cells) treated at the selected dose in an expanded cohort, in addition to the participants treated in Part 1. - Part 2b: To assess the efficacy in participants with metastatic TNBC and mild CA6 expression.

Secondary Objectives:

To assess:

• Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS), and Time To Progression (TTP).

• The impact of ocular primary prophylaxis on the incidence of keratopathies.

• The potential immunogenicity of SAR566658.

• To evaluate the global safety profile.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer	Drug: SAR566658 (ACT14884)	Phase 2

Detailed Description

The duration of the study for 1 participant included a screening period of up to 21 days prior to first study drug administration, 3-week treatment cycle(s) (until 30 days after last SAR566658 administration), and a follow-up period. Each participant was treated until radiological disease progression, unacceptable toxicity, or participant's refusal of further study treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label Phase 2 Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer
• Actual Study Start Date: Mar 23, 2017
• Actual Primary Completion Date: Sep 7, 2018
• Actual Study Completion Date: Sep 7, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAR566658 90 mg/m^2 Participants received SAR566658 90 milligram per square meter (mg/m^2) as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Drug: SAR566658 (ACT14884); Pharmaceutical form:Solution Route of administration: Intravenous
Experimental: SAR566658 120 mg/m^2 Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Drug: SAR566658 (ACT14884); Pharmaceutical form:Solution Route of administration: Intravenous

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings [Up to Cycle 2 (each cycle of 21 days)]

   Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (>=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade >=3 peripheral neuropathy (Preferred Term), Grade >=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.

2. Percentage of Participants With Objective Response [Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)]

   Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <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.

Secondary Outcome Measures

1. Percentage of Participants With Disease Control [Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)]

   Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in 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. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.

2. Duration of Response (DOR) [Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)]

   DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in 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. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.

3. Progression Free Survival (PFS) [Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)]

   PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.

4. Time to Tumor Progression (TTP) [Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)]

   TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

5. Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE) [Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)]

   AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.

6. Number of Participants With Keratopathies (Corneal Toxicity) [Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)]

   Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.

7. Number of Participants With Positive Anti-SAR566658 Antibodies Response [Up to 3 treatment cycles, each cycle 21 days]

Eligibility Criteria

Criteria

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

Inclusion criteria :

• Measurable Metastatic TNBC.

• Participants with CA6-positive disease.

• Participants received at least 1 prior chemotherapy regimen but no more than 3 for advanced/metastatic disease.

• Prior anticancer therapy must have contained anthracycline (eg, doxorubicin), if not contraindicated, and a taxane (eg, docetaxel, paclitaxel) in an adjuvant/neo-adjuvant or metastatic setting.

Exclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status >=2.

• Participant less than 18 years old.

• Pregnant or breast-feeding women.

• Participants with reproductive potential who do not agree to use accepted and effective method of contraception during the study treatment period and for 6 months following discontinuation of study drug.

• Wash out period of less than 3 weeks or 5 half-lives from previous antitumor chemotherapy, immunotherapy, or any investigational treatment.

• History of brain metastasis (other than totally resected or previously irradiated and nonprogressive/relapsed), spinal cord compression or carcinomatous meningitis, or new evidence of brain leptomeningeal disease.

• Prior treatment with eribulin as last prior therapy or prior maytansinoid treatments (DM1 or DM4 antibody-drug conjugates [ADCs]).

• Known intolerance to infused protein products including other monoclonal antibodies and ADCs.

• Poor bone marrow reserve and/or poor organ function.

• Symptomatic peripheral neuropathy Grade >=2.

• Previous history of chronic corneal diseases (even if asymptomatic) or unresolved acute nonrecurrent corneal conditions.

• Participants wearing contact lenses who are not willing to stop wearing them for the duration of the study.

• Medical conditions requiring concomitant administration of strong Cytochrome P450 3A4 (CYP3A4) inhibitors, unless it could be discontinued at least 2 weeks before 1st administration of SAR566658.

• Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 0560001	Leuven		Belgium	3000
2	Investigational Site Number 2030002	Praha 2		Czechia	12808
3	Investigational Site Number 3800003	Genova		Italy	16132
4	Investigational Site Number 3800001	Milano		Italy	20132
5	Investigational Site Number 3800004	Roma		Italy	00144
6	Investigational Site Number 5280001	Maastricht		Netherlands	6229 HX
7	Investigational Site Number 5280002	Rotterdam		Netherlands	3015 GD
8	Investigational Site Number 7240002	Barcelona		Spain	08035
9	Investigational Site Number 7240005	Lleida		Spain	25198
10	Investigational Site Number 7240001	Madrid		Spain	28034
11	Investigational Site Number 7240006	Madrid		Spain	28041
12	Investigational Site Number 7240003	Sevilla		Spain	41013
13	Investigational Site Number 7240004	Valencia		Spain	46010

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Dec 15, 2016
• Statistical Analysis Plan - May 29, 2018

More Information

Publications

None provided.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02984683
• Other Study ID Numbers: ACT14884; 2016-001962-27; U1111-1182-7044
• First Posted: Dec 7, 2016
• Last Update Posted: Sep 8, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms

Study Results

Participant Flow

Recruitment Details	The study was conducted at 13 sites in 5 countries from 23 March 2017 to 07 September 2018.
Pre-assignment Detail	A total of 23 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled in the study and included in Part 1. The study was prematurely terminated due to safety reasons, hence Part 2 was not conducted and no analysis was performed.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 milligram per square meter (mg/m^2) as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Period Title: Overall Study
STARTED	11	12
COMPLETED	0	0
NOT COMPLETED	11	12

Baseline Characteristics

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2	Total
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Total of all reporting groups
Overall Participants	11	12	23
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.73 (11.23)	50.33 (15.30)	53.39 (13.61)
Sex: Female, Male (Count of Participants)
Female	11 100%	12 100%	23 100%
Male	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	11 100%	12 100%	23 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings
Description	Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (>=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade >=3 peripheral neuropathy (Preferred Term), Grade >=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.
Time Frame	Up to Cycle 2 (each cycle of 21 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on participants evaluable for predefined safety criteria population which included participants treated in the study and had completed 2 cycles, or who experienced predefined safety criteria.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	9	9
Grade>=3 related TEAE from SOC Eye disorders	2 18.2%	2 16.7%
Grade>=3 related peripheral neuropathy	0 0%	0 0%
Grade>=4 related TEAE	0 0%	0 0%

2. Primary Outcome

Title	Percentage of Participants With Objective Response
Description	Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <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	Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on all-treated population which included participants who actually received at least 1 dose or any partial dose of SAR566658.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	11	12
Number (80% Confidence Interval) [percentage of participants]	9.1 82.7%	8.3 69.2%

3. Secondary Outcome

Title	Percentage of Participants With Disease Control
Description	Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in 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. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.
Time Frame	Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analyzed due to early termination of the study.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	0	0

4. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in 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. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame	Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analyzed due to early termination of the study.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	0	0

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.
Time Frame	Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analyzed due to early termination of the study.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	0	0

6. Secondary Outcome

Title	Time to Tumor Progression (TTP)
Description	TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time Frame	Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analyzed due to early termination of the study.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	0	0

7. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)
Description	AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.
Time Frame	Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on all treated population.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	11	12
Any TEAE	11 100%	12 100%
Any treatment emergent SAE	1 9.1%	6 50%
Any TEAE leading to treatment discontinuation	3 27.3%	3 25%

8. Secondary Outcome

Title	Number of Participants With Keratopathies (Corneal Toxicity)
Description	Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.
Time Frame	Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)

Outcome Measure Data

Analysis Population Description

Analysis was performed on all treated population.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	11	12
Count of Participants [Participants]	3 27.3%	5 41.7%

9. Secondary Outcome

Title	Number of Participants With Positive Anti-SAR566658 Antibodies Response
Time Frame	Up to 3 treatment cycles, each cycle 21 days

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not collected and analyzed due to early termination of the study.

Arm/Group Title	SAR566658 90 mg/m^2	SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).	Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
Measure Participants	0	0

Adverse Events

Time Frame	Adverse event (AE) data was collected from the baseline up to 3 treatment cycles, each cycle 21 days.
Adverse Event Reporting Description	Reported AEs are TEAEs i.e. AEs that developed/worsened during 'treatment period'(time from the first treatment administration to the last treatment administration + 30 days). Analysis was performed on safety population which included all participants who received at least 1 dose (or any partial dose) of SAR566658.
Arm/Group Title	SAR566658 90 mg/m^2		SAR566658 120 mg/m^2
Arm/Group Description	Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).		Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
All Cause Mortality
	SAR566658 90 mg/m^2		SAR566658 120 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/12 (0%)
Serious Adverse Events
	SAR566658 90 mg/m^2		SAR566658 120 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)		6/12 (50%)
Gastrointestinal disorders
Abdominal Pain	0/11 (0%)	0	1/12 (8.3%)	1
Pancreatitis Acute	0/11 (0%)	0	1/12 (8.3%)	1
General disorders
Pyrexia	0/11 (0%)	0	1/12 (8.3%)	1
Infections and infestations
Pneumonia	0/11 (0%)	0	1/12 (8.3%)	1
Respiratory Tract Infection	0/11 (0%)	0	1/12 (8.3%)	1
Staphylococcal Bacteraemia	1/11 (9.1%)	1	0/12 (0%)	0
Injury, poisoning and procedural complications
Ankle Fracture	0/11 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Hypercalcaemia	0/11 (0%)	0	1/12 (8.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Meninges	0/11 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/11 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	SAR566658 90 mg/m^2		SAR566658 120 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		12/12 (100%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)	0	1/12 (8.3%)	1
Ear and labyrinth disorders
Ear Pruritus	1/11 (9.1%)	1	0/12 (0%)	0
Endocrine disorders
Cushingoid	0/11 (0%)	0	1/12 (8.3%)	1
Eye disorders
Abnormal Sensation In Eye	1/11 (9.1%)	1	1/12 (8.3%)	1
Corneal Epithelial Microcysts	0/11 (0%)	0	1/12 (8.3%)	1
Corneal Opacity	0/11 (0%)	0	1/12 (8.3%)	1
Diplopia	1/11 (9.1%)	1	0/12 (0%)	0
Dry Eye	3/11 (27.3%)	3	1/12 (8.3%)	1
Halo Vision	1/11 (9.1%)	1	0/12 (0%)	0
Keratitis	5/11 (45.5%)	5	1/12 (8.3%)	1
Keratopathy	3/11 (27.3%)	3	5/12 (41.7%)	6
Periorbital Oedema	0/11 (0%)	0	1/12 (8.3%)	1
Photophobia	2/11 (18.2%)	2	0/12 (0%)	0
Vision Blurred	2/11 (18.2%)	2	1/12 (8.3%)	1
Vitreous Floaters	1/11 (9.1%)	1	0/12 (0%)	0
Xerophthalmia	1/11 (9.1%)	1	0/12 (0%)	0
Gastrointestinal disorders
Abdominal Pain	1/11 (9.1%)	1	0/12 (0%)	0
Constipation	3/11 (27.3%)	3	2/12 (16.7%)	2
Diarrhoea	0/11 (0%)	0	1/12 (8.3%)	1
Dry Mouth	1/11 (9.1%)	1	0/12 (0%)	0
Dyspepsia	0/11 (0%)	0	1/12 (8.3%)	1
Nausea	1/11 (9.1%)	1	2/12 (16.7%)	2
Odynophagia	1/11 (9.1%)	1	0/12 (0%)	0
Paraesthesia Oral	0/11 (0%)	0	1/12 (8.3%)	1
Stomatitis	0/11 (0%)	0	1/12 (8.3%)	1
Vomiting	0/11 (0%)	0	1/12 (8.3%)	1
General disorders
Asthenia	4/11 (36.4%)	4	3/12 (25%)	3
Device Related Thrombosis	1/11 (9.1%)	1	0/12 (0%)	0
Fatigue	1/11 (9.1%)	1	0/12 (0%)	0
Hyperthermia	1/11 (9.1%)	1	0/12 (0%)	0
Oedema Peripheral	0/11 (0%)	0	1/12 (8.3%)	1
Pain	1/11 (9.1%)	1	0/12 (0%)	0
Infections and infestations
Cystitis	1/11 (9.1%)	1	0/12 (0%)	0
Folliculitis	0/11 (0%)	0	1/12 (8.3%)	1
Gastrointestinal Infection	0/11 (0%)	0	1/12 (8.3%)	1
Nasopharyngitis	0/11 (0%)	0	1/12 (8.3%)	1
Periodontitis	1/11 (9.1%)	1	0/12 (0%)	0
Sinusitis	0/11 (0%)	0	1/12 (8.3%)	1
Skin Infection	1/11 (9.1%)	1	0/12 (0%)	0
Tonsillitis	1/11 (9.1%)	1	0/12 (0%)	0
Urinary Tract Infection	0/11 (0%)	0	1/12 (8.3%)	1
Injury, poisoning and procedural complications
Intentional Overdose	1/11 (9.1%)	2	0/12 (0%)	0
Investigations
Blood Bilirubin Increased	1/11 (9.1%)	1	0/12 (0%)	0
Transaminases Increased	2/11 (18.2%)	2	0/12 (0%)	0
Weight Decreased	0/11 (0%)	0	2/12 (16.7%)	2
Metabolism and nutrition disorders
Decreased Appetite	1/11 (9.1%)	1	3/12 (25%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	2/11 (18.2%)	2	2/12 (16.7%)	2
Muscle Spasms	0/11 (0%)	0	1/12 (8.3%)	1
Myalgia	1/11 (9.1%)	1	0/12 (0%)	0
Neck Pain	1/11 (9.1%)	1	1/12 (8.3%)	1
Nervous system disorders
Dysgeusia	0/11 (0%)	0	1/12 (8.3%)	1
Headache	1/11 (9.1%)	1	1/12 (8.3%)	2
Neuropathy Peripheral	2/11 (18.2%)	2	0/12 (0%)	0
Paraesthesia	2/11 (18.2%)	2	3/12 (25%)	3
Peripheral Sensory Neuropathy	0/11 (0%)	0	2/12 (16.7%)	2
Psychiatric disorders
Anxiety	0/11 (0%)	0	1/12 (8.3%)	1
Insomnia	1/11 (9.1%)	1	0/12 (0%)	0
Reproductive system and breast disorders
Breast Pain	1/11 (9.1%)	1	0/12 (0%)	0
Breast Ulceration	0/11 (0%)	0	1/12 (8.3%)	1
Metrorrhagia	1/11 (9.1%)	1	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/11 (0%)	0	3/12 (25%)	3
Pleural Effusion	0/11 (0%)	0	1/12 (8.3%)	1
Pulmonary Toxicity	0/11 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Onychomadesis	1/11 (9.1%)	1	0/12 (0%)	0
Palmar-Plantar Erythrodysaesthesia Syndrome	2/11 (18.2%)	2	0/12 (0%)	0
Pruritus Generalised	1/11 (9.1%)	1	0/12 (0%)	0
Rash	0/11 (0%)	0	1/12 (8.3%)	1
Vascular disorders
Hypertension	2/11 (18.2%)	2	0/12 (0%)	0

Limitations/Caveats

The study was prematurely discontinued considering the limited clinical benefit combined with higher than expected rate of known non-serious ophthalmological event, hence Part 2 was not conducted and some of pre-specified endpoints were not analyzed.

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Certain Agreements

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

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.