Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

NCT04659603 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: ACT16432U1111-1244-16442020-003096-18
• Study Type: interventional
• Target: 50
• Locations: 10 countries
• Sites: 29

Brief Summary

Primary Objective:

• For Cohort A, Cohort B, and Cohort C Part 2: To assess the antitumor activity of tusamitamab ravtansine in metastatic breast cancer (mBC) and tusamitamab ravtansine monotherapy and in combination with gemcitabine in metastatic pancreatic adenocarcinoma (mPAC)
• For Cohort C Part 1: Confirmation of the recommended tusamitamab ravtansine dose when administered in combination with gemcitabine Secondary Objectives:
• To assess the safety and tolerability of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
• To assess other efficacy parameters of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine
• To assess the immunogenicity of tusamitamab ravtansine
• To assess the pharmacokinetics (PK) of tusamitamab ravtansine and gemcitabine when given in combination

Conditions

Breast Cancer Metastatic; Pancreatic Carcinoma Metastatic

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  ORR was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. CR was defined as disappearance of all target and non-target lesions, and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

• Cohort C (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)

  The following adverse events (AEs) that occurred during the first cycle of treatment, unless due to disease progression or to a cause obviously unrelated to study treatment, were considered DLTs: 1. Hematological abnormalities: grade 4 neutropenia for 7 or more consecutive days, grade 3 to 4 neutropenia complicated by fever or microbiologically or radiographically documented infection, grade greater than or equal to (≥) 3 thrombocytopenia associated with clinically significant bleeding requiring clinical intervention; 2. Non-hematological abnormalities: grade 4 non-hematologic AE, grade ≥3 keratopathy. In addition, any other AE that the recruiting Investigators and Sponsor deemed to be dose limiting, regardless of its grade, was also considered as DLT.

  Cycle 1 (28 days)

Secondary Outcomes (10)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks

• Number of Participants With Laboratory Abnormalities: Hematology/Coagulation and Clinical Chemistry

  From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks

• Progression-free Survival (PFS)

  From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

• Disease Control Rate (DCR)

  From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

• Duration of Response (DOR)

  From date of first study treatment administration (Day 1) up to maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)

Study Arms (3)

Cohort A metastatic breast cancer (mBC)

EXPERIMENTAL

tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)

Drug: tusamitamab ravtansine

Cohort B metastatic pancreatic adenocarcinoma (mPAC)

EXPERIMENTAL

tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)

Drug: tusamitamab ravtansine

Cohort C Metastatic pancreatic adenocarcinoma (mPAC)

EXPERIMENTAL

tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)

Drug: tusamitamab ravtansine; Drug: Gemcitabine

Interventions

tusamitamab ravtansine DRUG

Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion

Also known as: SAR408701

Cohort A metastatic breast cancer (mBC); Cohort B metastatic pancreatic adenocarcinoma (mPAC); Cohort C Metastatic pancreatic adenocarcinoma (mPAC)

Gemcitabine DRUG

Pharmaceutical form: Lyophilized powder for reconstitution or as a solution for infusion; Route of administration: IV infusion

Cohort C Metastatic pancreatic adenocarcinoma (mPAC)

Eligibility Criteria

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

You may qualify if:

• Participant must be at least 18 years of age
• Participants with at least one measurable lesion according to the RECIST v1.1 criteria that has not been irradiated (ie, newly arising lesions in previously irradiated areas are accepted).
• Participants with ECOG performance status 0 to 1.
• Evidence of metastatic disease.
• Expression of CEACAM 5 by centrally assessed IHC assay.
• Male and female participants willing to comply with contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Cohort A: mBC
• Histological or cytologic diagnosis of breast cancer.
• Have received at least 2 prior cytotoxic chemotherapy regimens for non-TNBC tumor type or at least 1 for TNBC tumor type but not more than 4 in the locally recurrent or metastatic setting.
• Cohorts B and C: mPAC
• \- Have confirmed diagnosis of pancreatic ductal adenocarcinoma.
• Cohort B: mPAC:
• \- Have documented radiographic progression or documented intolerance after at least 1 prior systemic chemotherapy line which included either gemcitabine (or relapsed within 6 months of completion of gemcitabine adjuvant therapy) or a 5-fluorouracil based regimen (including capecitabine) but no more than 2 prior chemotherapy lines for locally advanced/metastatic disease.
• Cohort C: mPAC
• \- Have documented radiographic progression or documented intolerance after 1st line fluoropyrimidine-containing chemotherapy (or relapsed within 6 months of completion of chemotherapy as adjuvant therapy) for locally advanced/metastatic disease.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Medical condition requiring concomitant administration of a medication with a narrow therapeutic window, that is metabolized by cytochrome P450 (CYP450), 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 the first administration of study intervention.
• Life expectancy less than 3 months.
• Untreated brain metastases or history of leptomeningeal disease.
• Significant concomitant illness
• History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or active hepatitis A, B or C infection.
• Non-resolution of any prior treatment-related toxicity to \<Grade 2 according to NCI CTCAE v5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy (HRT).
• Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy.
• Use of contact lenses. Participants using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded.
• Concurrent treatment with any other anti cancer therapy.
• Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy, or any investigational treatment).
• Any prior therapy targeting CEACAM5.
• Prior maytansinoid DM4 treatment (ADC).

Sponsors & Collaborators

• Sanofi: lead

Study Sites (29)

AdventHealth Orlando Site Number : 8400001

Orlando, Florida, 32804, United States

Location

Massachusetts General Hospital Site Number : 8400002

Boston, Massachusetts, 02114, United States

Location

University of Wisconsin Site Number : 8400004

Madison, Wisconsin, 53792, United States

Location

Investigational Site Number : 0320003

Capital Federal, Buenos Aires, 1012, Argentina

Location

Investigational Site Number : 0320001

Pergamino, Buenos Aires, B2700CPM, Argentina

Location

Investigational Site Number : 0320002

Rosario, Santa Fe Province, 2000, Argentina

Location

Investigational Site Number : 1520002

Temuco, La Araucanía, 4800827, Chile

Location

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, 7500921, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8420383, Chile

Location

Investigational Site Number : 3480003

Budapest, 1122, Hungary

Location

Investigational Site Number : 5280002

Amsterdam, 1066 CX, Netherlands

Location

Investigational Site Number : 5280001

Rotterdam, 3015 GD, Netherlands

Location

Investigational Site Number : 5280003

Utrecht, 3584 CX, Netherlands

Location

Investigational Site Number : 6430001

Moscow, 115478, Russia

Location

Investigational Site Number : 6430004

Pushkin, Saint- Petersburg, 196603, Russia

Location

Investigational Site Number : 6430002

Saint Petersburg, 197758, Russia

Location

Investigational Site Number : 4100003

Goyang-si, Gyeonggi-do, 10408, South Korea

Location

Investigational Site Number : 4100001

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number : 4100002

Seoul, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240002

Majadahonda, Madrid, 28222, Spain

Location

Investigational Site Number : 7240003

Madrid, Madrid, Comunidad de, 28046, Spain

Location

Investigational Site Number : 1580001

Taichung, 40447, Taiwan

Location

Investigational Site Number : 1580002

Tainan, 704, Taiwan

Location

Investigational Site Number : 1580003

Taipei, 11217, Taiwan

Location

Investigational Site Number : 7920003

Adana, 01250, Turkey (Türkiye)

Location

Investigational Site Number : 7920004

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number : 7920001

Istanbul, 34722, Turkey (Türkiye)

Location

Investigational Site Number : 7920002

Izmir, Turkey (Türkiye)

Location

Related Links

• ACT16432 Plain Language Results Summary

MeSH Terms

Interventions

tusamitamab ravtansine; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The study was terminated due to the discontinuation of the overall development program of tusamitamab ravtansine (SAR408701) by the Sponsor on 20 December 2023.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 9, 2020
• Study Start: March 29, 2021
• Primary Completion: February 16, 2024
• Study Completion: January 19, 2025
• Last Updated: October 1, 2025
• Results First Posted: March 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); NL (3); TW (3); US (3); ES (3); RU (3); AR (3); TU (4); KR (3); CL (3)