Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer
- Conditions
- Triple Negative Breast Cancer
- Interventions
- Drug: SAR566658 (ACT14884)
- Registration Number
- NCT02984683
- Lead Sponsor
- Sanofi
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- Female
- Target Recruitment
- 23
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description SAR566658 120 mg/m^2 SAR566658 (ACT14884) 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). SAR566658 90 mg/m^2 SAR566658 (ACT14884) 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).
- Primary Outcome Measures
Name Time Method 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.
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
Name Time Method 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.
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.
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.
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.
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.
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.
Number of Participants With Positive Anti-SAR566658 Antibodies Response Up to 3 treatment cycles, each cycle 21 days
Trial Locations
- Locations (13)
Investigational Site Number 5280002
🇳🇱Rotterdam, Netherlands
Investigational Site Number 0560001
🇧🇪Leuven, Belgium
Investigational Site Number 2030002
🇨🇿Praha 2, Czechia
Investigational Site Number 3800003
🇮🇹Genova, Italy
Investigational Site Number 5280001
🇳🇱Maastricht, Netherlands
Investigational Site Number 3800004
🇮🇹Roma, Italy
Investigational Site Number 7240002
🇪🇸Barcelona, Spain
Investigational Site Number 7240005
🇪🇸Lleida, Spain
Investigational Site Number 7240006
🇪🇸Madrid, Spain
Investigational Site Number 3800001
🇮🇹Milano, Italy
Investigational Site Number 7240003
🇪🇸Sevilla, Spain
Investigational Site Number 7240001
🇪🇸Madrid, Spain
Investigational Site Number 7240004
🇪🇸Valencia, Spain