Evaluation of SAR408701 in Patients With Advanced Solid Tumors

Sponsor

Sanofi (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02187848

Collaborator

(none)

263

Enrollment

Locations

Arms

104.2

Anticipated Duration (Months)

10.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm Malignant	Drug: SAR408701	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

263 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Antitumor Activity of SAR408701 in Patients With Advanced Solid Tumors

Actual Study Start Date :

Jul 23, 2014

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SAR408701 Main Dose Escalation Cohort Dose escalation administered intravenously, once every two weeks	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Expansion Cohort colorectal cancer (CRC) Administered intravenously at the maximum tolerated dose (MTD), once every 2 weeks, to patients with colorectal cancer	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Expansion Cohort non-squamous NSCLC Administered 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	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Expansion Cohort gastric adenocarcinoma Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing gastric adenocarcinoma	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Loading Dose Escalation cohorts (Escalation bis) Loading dose escalation administered intravenously at first cycle, followed by MTD, once every 2 weeks	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Expansion Cohort non-squamous NSCLC (Lung bis) Administered 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	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Expansion Cohort colorectal cancer (CRC-L) Loading dose of determined MTD-L administered intravenously at first cycle, followed by MTD, once every 2 weeks	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Expansion Cohort small cell lung cancer (SCLC) Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing SCLC	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous
Experimental: SAR408701 Dose Escalation every 3 weeks cohort Dose escalation administered intravenously, once every three weeks	Drug: SAR408701 Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous

Outcome Measures

Primary Outcome Measures

Number of dose limiting adverse events (every 2 week cycle) [4 weeks]
Assessment of overall response rate using standard imaging and RECIST 1.1 criteria [Up to 40 months]
Number of dose limiting adverse events (every 3 week cycle) [3 weeks]

Secondary Outcome Measures

Number of treatment emergent adverse events [Up 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]
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 Q3W [2 months]
Mean systemic clearance (CL) [2 months]
Clearance at steady state (CLss) [2 months]
Accumulation ratio (Rac) on AUC0-14day and Cmax [2 months]
Detection of the development of anti-SAR408701 antibody [Up to 40 months]
Duration of response [Up to 40 months - assessment every 6-8 weeks]
Time to Progression [Up to 40 months - assessment every 6-8 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Locally advanced or metastatic solid malignant tumor disease for which no standard alternative therapy is available.
Availability of archived tumor tissue for carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5 or CEA) testing.
For participants in the Dose Escalation Cohorts (Main Escalation and Loading Dose Cohorts at every 2 week cycle and Dose Escalation every 3 week cycle): patients with tumors expressing or likely to be expressing CEACAM5 which includes colorectal cancer (CRC), non-squamous non-small cell lung cancer (NSCLC), gastric adenocarcinoma, squamous cell carcinoma of the cervix, pancreas adenocarcinoma, bladder transitional cell carcinoma, cholangiocarcinoma, epithelial ovarian cancer and endometrial adenocarcinoma are favored, or if carcinoembryonic antigen (CEA) plasma levels >5 ng/mL.
For participants to the Expansion Phase cohorts: patients with CRC or with CEACAM5 positive non-squamous NSCLC, small cell lung cancer (SCLC) or gastric carcinoma (including esophago-gastric junction adenocarcinoma of the Siewert types II and III).
At least one measurable lesion by RECIST v1.1 in the Expansion Phase only.
At least one lesion amenable to biopsy (Expansion cohort - CRC and gastric cancer only). Patient must consent to a baseline biopsy for retrospective confirmation of tumor CEACAM5 expression, except if NSCLC or SCLC without lesion amenable to biopsy.
Signed informed consent.

Exclusion criteria:

Aged less than 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status more than 1.
New or progressing brain involvement.
Concurrent treatment with any other anticancer therapy or inadequate wash-out period for prior anticancer therapies before first administration of SAR408701, or non-resolution of toxicities induced by these anticancer therapies.
Female or male patients with reproductive potential who do not agree to use an accepted effective method of contraception during the study treatment period and for at least 3 months following completion of study treatment.
Pregnancy or breast-feeding.
Participation to any clinical research study evaluating another investigational drug or therapy within 3 weeks of initiation of study regimen.
Prior therapy targeting CEACAM5.
Prior maytansinoid treatments (DM1 or DM4 antibody drug conjugates).
Poor bone marrow reserve resulting in low blood cell counts.
Poor kidney and liver functions.
Any of the following within 6 months prior to study enrolment: infectious or inflammatory bowel disease, diverticulitis, gastrointestinal perforation, intestinal obstruction, and gastrointestinal hemorrhage. Patients with malabsorption syndrome are excluded.
Previous history and or unresolved corneal disorders. The use of contact lenses is not permitted.
Unresolved signs and symptoms of neuropathy; Grade 1 is acceptable if prior neurotoxic drugs such as cisplatin or taxanes.
Abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) of <50%.
Cardiac conduction defects, or any other clinically significant arrhythmias.
Known intolerance to infused protein products.
Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by cytochrome P450 (CYPs) enzymes 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 1st administration of SAR408701.
Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid as per package insert of each drug, including the following: increase intraocular pressure, prior or current glaucoma, narrow-angle glaucoma, ongoing eye infection, uncontrolled hypertension, known/suspected allergy to constituents of the preparation (such as sodium bisulfite).

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 840006	Bakersfield	California	United States	93309
2	Investigational Site Number 840003	Santa Monica	California	United States	90404
3	Investigational Site Number 840002	New Haven	Connecticut	United States	06520-8017
4	Investigational Site Number 840105	Boston	Massachusetts	United States	02114
5	Investigational Site Number 840005	Boston	Massachusetts	United States	02115
6	Investigational Site Number 840001	Hackensack	New Jersey	United States	07601
7	Investigational Site Number 124001	Toronto		Canada	M5G 2M9
8	Investigational Site Number 250003	Bordeaux Cedex		France	33076
9	Investigational Site Number 250006	Dijon		France	21079
10	Investigational Site Number 250004	Marseille Cedex 5		France	13385
11	Investigational Site Number 250007	Rennes		France	35000
12	Investigational Site Number 250005	Saint Mande		France	94163
13	Investigational Site Number 250002	Toulouse Cedex 9		France	31059
14	Investigational Site Number 250001	Villejuif Cedex		France	94805
15	Investigational Site Number 410002	Seoul		Korea, Republic of	03080
16	Investigational Site Number 410005	Seoul		Korea, Republic of	03722
17	Investigational Site Number 410003	Seoul		Korea, Republic of	06351
18	Investigational Site Number 410004	Seoul		Korea, Republic of	07061
19	Investigational Site Number 410001	Seoul		Korea, Republic of	138-736
20	Investigational Site Number 724001	Barcelona		Spain	08035
21	Investigational Site Number 724007	Madrid		Spain	28034
22	Investigational Site Number 724004	Madrid		Spain	28040
23	Investigational Site Number 724006	Madrid		Spain	28041
24	Investigational Site Number 724003	Madrid		Spain	28050
25	Investigational Site Number 724002	Majadahonda		Spain	28222

Sponsors and Collaborators

Sanofi

Investigators

Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sanofi

ClinicalTrials.gov Identifier:

NCT02187848

Other Study ID Numbers:

TED13751
2014-001130-29

First Posted:

Jul 11, 2014

Last Update Posted:

Jul 14, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Jul 14, 2022