Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

A Phase I Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy in Japanese Patients With Advanced Malignant Solid Tumors

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.

Study Overview

• Status: Completed
• Conditions: Neoplasm Malignant
• Intervention / Treatment: Drug: SAR408701; Drug: dexamethasone; Drug: naphazoline; Drug: diphenhydramine

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 Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kashiwa-Shi, Japan
    • Investigational Site Number 3920003
  • Nagoya-Shi, Japan
    • Investigational Site Number 3920002
  • Sunto-Gun, Japan
    • Investigational Site Number 3920001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Tusamitamab ravtansine; Drug: dexamethasone; Pharmaceutical form: solution for eye drop Route of administration: eye drop; Other Names: Santeson ophthalmic solution; Drug: naphazoline; Pharmaceutical form: solution for eye drop Route of administration: eye drop; Other Names: Clearine; Drug: diphenhydramine; Pharmaceutical form: tablet Route of administration: oral; Other Names: Restamin Kowa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IMP-related dose limiting toxicities (DLT)	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	4 weeks, Dose escalation q3w part: 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment emergent adverse events	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	Up to an average of 9 months
Maximum observed concentration (Cmax) of SAR408701	Cmax for SAR408701 will be assessed after single and repeat doses, as relevant	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 of DM4 and Me-DM4	Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant	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)
Time to reach maximum concentration (Tmax) of SAR408701	Tmax for SAR408701 will be assessed after single and repeat doses, as relevant	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 of DM4 and Me-DM4	Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant	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)
Area under the concentration-time curve (AUC) of SAR408701	AUC of SAR408701 from time zero extrapolated to infinity	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	AUC of DM4 and Me-DM4 from time zero extrapolated to infinity	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)
Assessment of PDy effect	Assessment of plasma CEACAM5 levels in main dose-escalation part	Up to an average of 10 months
Assessment of anti-tumor activity	Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria	Up to an average of 10 months
Detection of anti-SAR408701 antibody	Immunogenicity evaluation for anti-SAR408701 antibodies	Up to an average of 10 months

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2017
• Primary Completion (Actual): November 18, 2022
• Study Completion (Actual): December 26, 2022

Study Registration Dates

• First Submitted: October 6, 2017
• First Submitted That Met QC Criteria: October 24, 2017
• First Posted (Actual): October 27, 2017

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 6, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Adrenergic alpha-Agonists; Adrenergic Agonists; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Respiratory System Agents; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Pharmaceutical Solutions; Vasoconstrictor Agents; Nasal Decongestants; Dexamethasone; Diphenhydramine; Promethazine; Ophthalmic Solutions; Naphazoline
• Other Study ID Numbers: TCD15054; U1111-1191-5464 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No