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Evaluation of SAR408701 in Patients With Advanced Solid Tumors

Phase 1
Terminated
Conditions
Neoplasm Malignant
Interventions
Registration Number
NCT02187848
Lead Sponsor
Sanofi
Brief Summary

Primary Objectives:

* To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 2 weeks (with and without a loading dose at Cycle 1) to patients with advanced solid tumors (Main Escalation and Loading Dose Escalation Q2W).

* To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 3 weeks to patients with advanced solid tumors (Escalation Q3W Cycle).

* To assess efficacy according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Expansion Phase) when SAR408701 is administered once every 2 weeks with or without a loading dose at Cycle 1.

Secondary Objectives:

* To characterize the overall safety profile of SAR408701.

* To characterize the pharmacokinetic (PK) profile of SAR408701 and of its potential circulating derivatives.

* To identify the recommended phase 2 dose (RP2D) of SAR408701.

* To assess the potential immunogenicity of SAR408701.

Detailed Description

The study duration for an individual patient will start from the signature of the informed consent, 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 visit around 30 days following the last administration of study drug, and at least one follow-up visit after the end-of-treatment visit. Additional follow-up visits may be required until resolution or stabilization of adverse events (at least 30 days). Treatment may continue until precluded by toxicity, progression, or upon patient's request. If the patient stops study treatment for reason other than disease progression, follow-up visit will be performed every 3 months until disease progression or initiation of another anti-tumor treatment or death, whichever comes first.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
254
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAR408701 Expansion Cohort gastric adenocarcinomaSAR408701Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing gastric adenocarcinoma
SAR408701 Loading Dose Escalation cohorts (Escalation bis)SAR408701Loading dose escalation administered intravenously at first cycle, followed by MTD, once every 2 weeks
SAR408701 Expansion Cohort non-squamous NSCLC (Lung bis)SAR408701Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing non-squamous NSCLC of at least 1% but below 50% of tumor cells at or above 2+ intensity
SAR408701 Main Dose Escalation CohortSAR408701Dose escalation administered intravenously, once every two weeks
SAR408701 Expansion Cohort colorectal cancer (CRC)SAR408701Administered intravenously at the maximum tolerated dose (MTD), once every 2 weeks, to patients with colorectal cancer
SAR408701 Expansion Cohort non-squamous NSCLCSAR408701Administered intravenously at the MTD, once every 2 weeks, to patients with carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expressing non-squamous non-small cell lung cancer (NSCLC) of at least 50% of tumor cells at or above 2+ intensity
SAR408701 Expansion Cohort colorectal cancer (CRC-L)SAR408701Loading dose of determined MTD-L administered intravenously at first cycle, followed by MTD, once every 2 weeks
SAR408701 Expansion Cohort small cell lung cancer (SCLC)SAR408701Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing SCLC
SAR408701 Dose Escalation every 3 weeks cohortSAR408701Dose escalation administered intravenously, once every three weeks
Primary Outcome Measures
NameTimeMethod
Number of dose limiting adverse events (every 2 week cycle)4 weeks
Assessment of overall response rate using standard imaging and RECIST 1.1 criteriaUp to 40 months
Number of dose limiting adverse events (every 3 week cycle)3 weeks
Secondary Outcome Measures
NameTimeMethod
Duration of responseUp to 40 months - assessment every 6-8 weeks
Number of treatment emergent adverse eventsUp to 4 years
Maximum concentration (Cmax)2 months
Time to reach maximum concentration (tmax)2 months
Trough plasma concentrations (Ctrough)Intensive testing within first 2 months, then every 2 weeks
Accumulation ratio (Rac) on AUC0-14day and Cmax2 months
Area under the plasma concentration versus time curve between 0 and 14 days (AUC0-14day) for Q2W or between 0 and 21 days (AUC-21 day) for Q3W2 months
Mean systemic clearance (CL)2 months
Clearance at steady state (CLss)2 months
Detection of the development of anti-SAR408701 antibodyUp to 40 months
Time to ProgressionUp to 40 months - assessment every 6-8 weeks

Trial Locations

Locations (20)

Dana Farber Cancer Institute- Site Number : 840005

🇺🇸

Boston, Massachusetts, United States

Yale University School of Medicine Site Number : 840002

🇺🇸

New Haven, Connecticut, United States

Investigational Site Number : 124001

🇨🇦

Toronto, Ontario, Canada

Investigational Site Number : 250003

🇫🇷

Bordeaux Cedex, France

Investigational Site Number : 250006

🇫🇷

Dijon, France

Investigational Site Number : 250004

🇫🇷

Marseille, France

Investigational Site Number : 250007

🇫🇷

Rennes, France

Investigational Site Number : 250005

🇫🇷

Saint Mande, France

Investigational Site Number : 250002

🇫🇷

TOULOUSE Cedex 9, France

Investigational Site Number : 250001

🇫🇷

Villejuif, France

Investigational Site Number : 410002

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 410005

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 410003

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 410004

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 410001

🇰🇷

Seoul, Seoul-teukbyeolsi, Korea, Republic of

Investigational Site Number : 724001

🇪🇸

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 724004

🇪🇸

Madrid / Madrid, Madrid, Comunidad De, Spain

Investigational Site Number : 724003

🇪🇸

Madrid, Madrid, Comunidad De, Spain

Investigational Site Number : 724002

🇪🇸

Majadahonda, Madrid, Spain

Investigational Site Number : 724006

🇪🇸

Madrid, Spain

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