Evaluation of SAR408701 in Patients With Advanced Solid Tumors

NCT02187848 | Terminated Phase 1

• 3 other identifiers: TED13751U1111-1153-34612014-001130-29
• Study Type: interventional
• Target: 254
• Locations: 5 countries
• Sites: 20

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.

Conditions

Neoplasm Malignant

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• 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

Study Arms (9)

SAR408701 Main Dose Escalation Cohort

EXPERIMENTAL

Dose escalation administered intravenously, once every two weeks

Drug: SAR408701

SAR408701 Expansion Cohort colorectal cancer (CRC)

EXPERIMENTAL

Administered intravenously at the maximum tolerated dose (MTD), once every 2 weeks, to patients with colorectal cancer

Drug: SAR408701

SAR408701 Expansion Cohort non-squamous NSCLC

EXPERIMENTAL

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

SAR408701 Expansion Cohort gastric adenocarcinoma

EXPERIMENTAL

Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing gastric adenocarcinoma

Drug: SAR408701

SAR408701 Loading Dose Escalation cohorts (Escalation bis)

EXPERIMENTAL

Loading dose escalation administered intravenously at first cycle, followed by MTD, once every 2 weeks

Drug: SAR408701

SAR408701 Expansion Cohort non-squamous NSCLC (Lung bis)

EXPERIMENTAL

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

SAR408701 Expansion Cohort colorectal cancer (CRC-L)

EXPERIMENTAL

Loading dose of determined MTD-L administered intravenously at first cycle, followed by MTD, once every 2 weeks

Drug: SAR408701

SAR408701 Expansion Cohort small cell lung cancer (SCLC)

EXPERIMENTAL

Administered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing SCLC

Drug: SAR408701

SAR408701 Dose Escalation every 3 weeks cohort

EXPERIMENTAL

Dose escalation administered intravenously, once every three weeks

Drug: SAR408701

Interventions

SAR408701 DRUG

Pharmaceutical form: concentrate for solution for infusion Route of administration: intravenous

SAR408701 Dose Escalation every 3 weeks cohort; SAR408701 Expansion Cohort colorectal cancer (CRC); SAR408701 Expansion Cohort colorectal cancer (CRC-L); SAR408701 Expansion Cohort gastric adenocarcinoma; SAR408701 Expansion Cohort non-squamous NSCLC; SAR408701 Expansion Cohort non-squamous NSCLC (Lung bis); SAR408701 Expansion Cohort small cell lung cancer (SCLC); SAR408701 Loading Dose Escalation cohorts (Escalation bis); SAR408701 Main Dose Escalation Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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%.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (20)

Yale University School of Medicine Site Number : 840002

New Haven, Connecticut, 06520-8017, United States

Location

Dana Farber Cancer Institute- Site Number : 840005

Boston, Massachusetts, 02115, United States

Location

Investigational Site Number : 124001

Toronto, Ontario, M5G 2M9, Canada

Location

Investigational Site Number : 250003

Bordeaux, 33076, France

Location

Investigational Site Number : 250006

Dijon, 21079, France

Location

Investigational Site Number : 250004

Marseille, 13385, France

Location

Investigational Site Number : 250007

Rennes, 35000, France

Location

Investigational Site Number : 250005

Saint-Mandé, 94163, France

Location

Investigational Site Number : 250002

Toulouse, 31059, France

Location

Investigational Site Number : 250001

Villejuif, 94800, France

Location

Investigational Site Number : 410002

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 410005

Seoul, Seoul-teukbyeolsi, 03722, South Korea

Location

Investigational Site Number : 410003

Seoul, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 410004

Seoul, Seoul-teukbyeolsi, 07061, South Korea

Location

Investigational Site Number : 410001

Seoul, Seoul-teukbyeolsi, 138-736, South Korea

Location

Investigational Site Number : 724001

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 724002

Majadahonda, Madrid, 28222, Spain

Location

Investigational Site Number : 724003

Madrid, Madrid, Comunidad de, 28050, Spain

Location

Investigational Site Number : 724004

Madrid / Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number : 724006

Madrid, 28041, Spain

Location

Related Publications (3)

• Gazzah A, Bedard PL, Hierro C, Kang YK, Abdul Razak A, Ryu MH, Demers B, Fagniez N, Henry C, Hospitel M, Soria JC, Tabernero J. Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. Ann Oncol. 2022 Apr;33(4):416-425. doi: 10.1016/j.annonc.2021.12.012. Epub 2022 Jan 10.

  PMID: 35026412 RESULT

• Tabernero J, Bedard PL, Bang YJ, Vieito M, Ryu MH, Fagniez N, Chadjaa M, Soufflet C, Masson N, Gazzah A. Tusamitamab Ravtansine in Patients with Advanced Solid Tumors: Phase I Study of Safety, Pharmacokinetics, and Antitumor Activity Using Alternative Dosing Regimens. Cancer Res Commun. 2023 Aug 28;3(8):1662-1671. doi: 10.1158/2767-9764.CRC-23-0284. eCollection 2023 Aug.

  PMID: 37645622 RESULT

• Gazzah A, Ternes N, Lee JS, Wang E, Carene D, Wang H, Masson N, Boitier E, Lartigau A, Mace N, Chadjaa M, Dib C, Nunes M, Muzard G, Longuemaux-Valence S, Bauchet AL. Biomarker analysis from a Phase 1/1b study of tusamitamab ravtansine in patients with advanced non-small cell lung cancer. Transl Oncol. 2026 Jan;63:102615. doi: 10.1016/j.tranon.2025.102615. Epub 2025 Dec 3.

  PMID: 41337813 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

tusamitamab ravtansine

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: July 11, 2014
• Study Start: July 23, 2014
• Primary Completion: November 10, 2020
• Study Completion: November 19, 2024
• Last Updated: February 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share

Locations

US (2); CA (1); ES (5); FR (7); KR (5)