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Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

Phase 1
Completed
Conditions
Neoplasm Malignant
Interventions
Registration Number
NCT03324113
Lead Sponsor
Sanofi
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:

* 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
34
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
SAR408701 MonotherapySAR408701SAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors
SAR408701 MonotherapydiphenhydramineSAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors
SAR408701 MonotherapydexamethasoneSAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors
SAR408701 MonotherapynaphazolineSAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Time to reach maximum concentration (Tmax) of SAR408701Main 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

Assessment of anti-tumor activityUp to an average of 10 months

Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria

Treatment emergent adverse eventsUp 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

AUC of DM4 and Me-DM4Main 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 effectUp to an average of 10 months

Assessment of plasma CEACAM5 levels in main dose-escalation part

Cmax of DM4 and Me-DM4Main 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

Detection of anti-SAR408701 antibodyUp to an average of 10 months

Immunogenicity evaluation for anti-SAR408701 antibodies

Area under the concentration-time curve (AUC) of SAR408701Main 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

Maximum observed concentration (Cmax) of SAR408701Main 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

Tmax of DM4 and Me-DM4Main 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

Trial Locations

Locations (3)

Investigational Site Number 3920002

🇯🇵

Nagoya-Shi, Japan

Investigational Site Number 3920003

🇯🇵

Kashiwa-Shi, Japan

Investigational Site Number 3920001

🇯🇵

Sunto-Gun, Japan

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