E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10075566 |
E.1.2 | Term | Triple negative breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To select in the first part the SAR566658 dose based on Objective Response Rate (ORR) and safety of 2 dose levels and to demonstrate in the second part the efficacy of the selected dose based on ORR. |
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E.2.2 | Secondary objectives of the trial |
- To assess:
- Disease Control Rate (DCR), Duration Of Response (DOR), Progression-Free Survival (PFS), and Time To Progression (TTP) ;
- The PK profile of SAR566658
- The impact of ocular primary prophylaxis on the incidence of keratopathies ;
- The potential immunogenicity of SAR566658 ;
- The relationship between CA6 expression level in the tumor, and circulating CA6 in
blood at baseline, and efficacy outcomes
- To evaluate the global safety profile. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Measurable Metastatic triple negative breast cancer (TNBC).
-Patients with CA6-positive disease.
-Patients 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. |
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E.4 | Principal exclusion criteria |
-Eastern Cooperative Oncology Group (ECOG) performance status ≥2.
-Patient less than 18 years old.
-Pregnant or breast-feeding women.
-Patients 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.
-Patients wearing contact lenses who are not willing to stop wearing them for the duration of the study.
-Medical conditions requiring concomitant administration of strong CYP3A4 inhibitors, unless it can be discontinued at least 2 weeks before 1st administration of SAR566658.
-Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1/ Disease control rate
2/ Duration of response - time
3/ Progression free survival - time
4/ Time to progression
5/ Number of keratopathies
6/ Incidence of positive patients for antidrug antibodies as a measure of SAR566658 immunogenicity |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2 : at 18 months
3-4 : at 2 years
5 : Up to 30 days after the 3-week treatment cycle(s) (until 30 days after last treatment administration)
6 : Up to 60 days after the 3-week treatment cycle(s) (until 60 days after last treatment administration) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
France |
Italy |
Netherlands |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |