Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors
Study Details
Study Description
Brief Summary
Primary Objective:
- To evaluate tolerability and safety of SAR408701 when administered as a single agent according to the investigational medicinal product (IMP) related dose limiting toxicities (DLTs) to determine the recommended dose (RD) of SAR408701 in Japanese patients with advanced malignant solid tumors.
Secondary Objectives:
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To characterize the overall safety profile of SAR408701 monotherapy.
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To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites.
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To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for main dose escalation part.
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To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria and other indicators of antitumor activity.
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To assess the potential immunogenicity of SAR408701.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The study duration per participant will include a period to assess eligibility (screening period) of up to approximately 4 weeks (28 days), a treatment period and an End-of-Treatment (EOT) visit around 30 days after the last administration of IMP, and at least one follow-up (FU) visit after the EOT visit.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SAR408701 Monotherapy SAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors |
Drug: SAR408701
Pharmaceutical form: solution for infusion
Route of administration: intravenous
Other Names:
Drug: dexamethasone
Pharmaceutical form: solution for eye drop
Route of administration: eye drop
Other Names:
Drug: naphazoline
Pharmaceutical form: solution for eye drop
Route of administration: eye drop
Other Names:
Drug: diphenhydramine
Pharmaceutical form: tablet
Route of administration: oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- IMP-related dose limiting toxicities (DLT) [4 weeks, Dose escalation q3w part: 3 weeks]
IMP-related DLTs are defined as adverse events (AE) related to the IMPs in absence of clear evidence to the contrary, after validation by the Study Committee, and if not related to a disease progression, graded using National Cancer Institute common Toxicity Criteria (NCI-CTC) scale v4.03
Secondary Outcome Measures
- Treatment emergent adverse events [Up to an average of 9 months]
Overall safety profile characterized in terms of the type, frequency, severity, seriousness, and relationship to study therapy of any AEs based on standard and systematic assessment including physical findings, laboratory tests or other investigations
- Maximum observed concentration (Cmax) of SAR408701 [Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)]
Cmax for SAR408701 will be assessed after single and repeat doses, as relevant
- Cmax of DM4 and Me-DM4 [Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)]
Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant
- Time to reach maximum concentration (Tmax) of SAR408701 [Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)]
Tmax for SAR408701 will be assessed after single and repeat doses, as relevant
- Tmax of DM4 and Me-DM4 [Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)]
Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant
- Area under the concentration-time curve (AUC) of SAR408701 [Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)]
AUC of SAR408701 from time zero extrapolated to infinity
- AUC of DM4 and Me-DM4 [Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days), Dose-escalation q3w part: Cycle 1 and Cycle2 day 1 (Cycle 1 is 21 days)]
AUC of DM4 and Me-DM4 from time zero extrapolated to infinity
- Assessment of PDy effect [Up to an average of 10 months]
Assessment of plasma CEACAM5 levels in main dose-escalation part
- Assessment of anti-tumor activity [Up to an average of 10 months]
Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria
- Detection of anti-SAR408701 antibody [Up to an average of 10 months]
Immunogenicity evaluation for anti-SAR408701 antibodies
Eligibility Criteria
Criteria
Inclusion criteria:
-
Locally advanced or metastatic solid malignant tumor disease for which, in the judgement of the investigator, no standard alternative therapy is available.
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Inclusion is likely to be expressing CEACAM5.
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At least 6 x 5 μm slides from formalin-fixed paraffin-embedded (FFPE) archival tissue should be available for retrospective central evaluation of CEACAM5 expression.
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Patient understands and has signed the Written Informed Consent form and is willing and able to comply with the requirements of the trial.
Exclusion criteria:
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Patient less than 20 years old.
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2.
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Life expectancy <12 weeks.
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Known or symptomatic brain metastasis (other than totally resected or previously irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.
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Female patients of childbearing potential and male patients with female partners of childbearing 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 IMP.
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Significant concomitant illnesses, including all severe medical conditions which, in the opinion of the Investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results.
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Prior therapy targeting CEACAM5.
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Prior maytansinoid treatments (maytansinoid derivative 1 [DM1] or maytansinoid derivative 4 [DM4] antibody drug conjugates).
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Previous history and or unresolved corneal disorders.
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Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by cytochrome P450 (CYP) and for which a dose reduction cannot be considered.
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Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before first administration of SAR408701.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 3920003 | Kashiwa-Shi | Japan | ||
| 2 | Investigational Site Number 3920002 | Nagoya-Shi | Japan | ||
| 3 | Investigational Site Number 3920001 | Sunto-Gun | Japan |
Sponsors and Collaborators
- Sanofi
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TCD15054
- U1111-1191-5464