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

NCT02984683 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: ACT148842016-001962-27U1111-1182-7044
• Study Type: interventional
• Target: 23
• Locations: 5 countries
• Sites: 13

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.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings

  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.

  Up to Cycle 2 (each cycle of 21 days)

• Percentage of Participants With Objective Response

  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.

  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)

Secondary Outcomes (7)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (2)

SAR566658 90 mg/m^2

EXPERIMENTAL

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)

SAR566658 120 mg/m^2

EXPERIMENTAL

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)

Interventions

SAR566658 (ACT14884) DRUG

Pharmaceutical form:Solution Route of administration: Intravenous

SAR566658 120 mg/m^2; SAR566658 90 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (13)

Investigational Site Number 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number 2030002

Prague, 12808, Czechia

Location

Investigational Site Number 3800003

Genova, 16132, Italy

Location

Investigational Site Number 3800001

Milan, 20132, Italy

Location

Investigational Site Number 3800004

Roma, 00144, Italy

Location

Investigational Site Number 5280001

Maastricht, 6229 HX, Netherlands

Location

Investigational Site Number 5280002

Rotterdam, 3015 GD, Netherlands

Location

Investigational Site Number 7240002

Barcelona, 08035, Spain

Location

Investigational Site Number 7240005

Lleida, 25198, Spain

Location

Investigational Site Number 7240001

Madrid, 28034, Spain

Location

Investigational Site Number 7240006

Madrid, 28041, Spain

Location

Investigational Site Number 7240003

Seville, 41013, Spain

Location

Investigational Site Number 7240004

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

SAR-566658

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and 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.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2016
• First Posted: December 7, 2016
• Study Start: March 23, 2017
• Primary Completion: September 7, 2018
• Study Completion: September 7, 2018
• Last Updated: September 8, 2021
• Results First Posted: September 8, 2021

Record last verified: 2021-08

Locations

NL (2); ES (6); CZ (1); IT (3); BE (1)