Description:
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:
- To characterize the overall safety profile of SAR408701 monotherapy.
- To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites.
- 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.
- To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor
(RECIST) 1.1 criteria and other indicators of antitumor activity.
- To assess the potential immunogenicity of SAR408701.
Title
- Brief Title: Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors
- Official Title: A Phase I Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy in Japanese Patients With Advanced Malignant Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
TCD15054
- SECONDARY ID:
U1111-1191-5464
- NCT ID:
NCT03324113
Conditions
Interventions
Drug | Synonyms | Arms |
---|
SAR408701 | Tusamitamab ravtansine | SAR408701 Monotherapy |
dexamethasone | Santeson ophthalmic solution | SAR408701 Monotherapy |
naphazoline | Clearine | SAR408701 Monotherapy |
diphenhydramine | Restamin Kowa | SAR408701 Monotherapy |
Purpose
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:
- To characterize the overall safety profile of SAR408701 monotherapy.
- To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites.
- 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.
- To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor
(RECIST) 1.1 criteria and other indicators of antitumor activity.
- To assess the potential immunogenicity of SAR408701.
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.
Trial Arms
Name | Type | Description | Interventions |
---|
SAR408701 Monotherapy | Experimental | SAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors | - SAR408701
- dexamethasone
- naphazoline
- diphenhydramine
|
Eligibility 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.
- Inclusion is likely to be expressing CEACAM5.
- 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.
- 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:
- Patient less than 20 years old.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2.
- Life expectancy <12 weeks.
- Known or symptomatic brain metastasis (other than totally resected or previously
irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.
- 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.
- 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.
- Prior therapy targeting CEACAM5.
- Prior maytansinoid treatments (maytansinoid derivative 1 [DM1] or maytansinoid
derivative 4 [DM4] antibody drug conjugates).
- Previous history and or unresolved corneal disorders.
- 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.
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 20 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | IMP-related dose limiting toxicities (DLT) |
Time Frame: | 4 weeks, Dose escalation q3w part: 3 weeks |
Safety Issue: | |
Description: | 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
Measure: | Treatment emergent adverse events |
Time Frame: | Up to an average of 9 months |
Safety Issue: | |
Description: | 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 |
Measure: | Maximum observed concentration (Cmax) of SAR408701 |
Time Frame: | 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) |
Safety Issue: | |
Description: | Cmax for SAR408701 will be assessed after single and repeat doses, as relevant |
Measure: | Cmax of DM4 and Me-DM4 |
Time Frame: | 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) |
Safety Issue: | |
Description: | Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant |
Measure: | Time to reach maximum concentration (Tmax) of SAR408701 |
Time Frame: | 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) |
Safety Issue: | |
Description: | Tmax for SAR408701 will be assessed after single and repeat doses, as relevant |
Measure: | Tmax of DM4 and Me-DM4 |
Time Frame: | 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) |
Safety Issue: | |
Description: | Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant |
Measure: | Area under the concentration-time curve (AUC) of SAR408701 |
Time Frame: | 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) |
Safety Issue: | |
Description: | AUC of SAR408701 from time zero extrapolated to infinity |
Measure: | AUC of DM4 and Me-DM4 |
Time Frame: | 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) |
Safety Issue: | |
Description: | AUC of DM4 and Me-DM4 from time zero extrapolated to infinity |
Measure: | Assessment of PDy effect |
Time Frame: | Up to an average of 10 months |
Safety Issue: | |
Description: | Assessment of plasma CEACAM5 levels in main dose-escalation part |
Measure: | Assessment of anti-tumor activity |
Time Frame: | Up to an average of 10 months |
Safety Issue: | |
Description: | Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria |
Measure: | Detection of anti-SAR408701 antibody |
Time Frame: | Up to an average of 10 months |
Safety Issue: | |
Description: | Immunogenicity evaluation for anti-SAR408701 antibodies |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Sanofi |
Last Updated
July 1, 2021