Tusamitamab Ravtansine Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors (CARMEN-BT01)

Open-label, Multi-cohort, Phase 2 Trial, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine (SAR408701) Monotherapy and in Combination in Patients With CEACAM5-positive Advanced Solid Tumors

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

Study Overview

• Status: Terminated
• Conditions: Breast Cancer Metastatic; Pancreatic Carcinoma Metastatic
• Intervention / Treatment: Drug: tusamitamab ravtansine; Drug: Gemcitabine

Detailed Description

The expected duration of study intervention for participants may vary, based on progression date and the cohort; median expected duration of study per participant is estimated at 8 months for Cohort A/C and 6 months for Cohort B (up to 1 month for screening, a median of 4 or 2 months for treatment in Cohort A/C and Cohort B respectively, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Capital Federal, Buenos Aires, Argentina, 1012
      • Investigational Site Number : 0320003
    • Pergamino, Buenos Aires, Argentina, B2700CPM
      • Investigational Site Number : 0320001
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Investigational Site Number : 0320002
• Chile
  • La Araucanía
    • Temuco, La Araucanía, Chile, 4800827
      • Investigational Site Number : 1520002
  • Reg Metropolitana de Santiago
    • Santiago, Reg Metropolitana de Santiago, Chile, 8420383
      • Investigational Site Number : 1520001
    • Santiago, Reg Metropolitana de Santiago, Chile, 7500921
      • Investigational Site Number : 1520003
• Hungary
  • Budapest, Hungary, 1122
    • Investigational Site Number : 3480003
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Investigational Site Number : 5280002
  • Rotterdam, Netherlands, 3015 GD
    • Investigational Site Number : 5280001
  • Utrecht, Netherlands, 3584 CX
    • Investigational Site Number : 5280003
• Russia
  • Moscow, Russia, 115478
    • Investigational Site Number : 6430001
  • Pushkin, Saint- Petersburg, Russia, 196603
    • Investigational Site Number : 6430004
  • Saint Petersburg, Russia, 197758
    • Investigational Site Number : 6430002
• South Korea
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, South Korea, 10408
      • Investigational Site Number : 4100003
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, South Korea, 03080
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, South Korea, 06351
      • Investigational Site Number : 4100002
• Spain
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Investigational Site Number : 7240001
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Investigational Site Number : 7240002
  • Madrid, Comunidad de
    • Madrid, Madrid, Comunidad de, Spain, 28046
      • Investigational Site Number : 7240003
• Taiwan
  • Taichung, Taiwan, 40447
    • Investigational Site Number : 1580001
  • Tainan City, Taiwan, 704
    • Investigational Site Number : 1580002
  • Taipei, Taiwan, 11217
    • Investigational Site Number : 1580003
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01250
    • Investigational Site Number : 7920003
  • Ankara, Turkey (Türkiye), 06100
    • Investigational Site Number : 7920004
  • Istanbul, Turkey (Türkiye), 34722
    • Investigational Site Number : 7920001
  • Izmir, Turkey (Türkiye)
    • Investigational Site Number : 7920002
• United States
  • Florida
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando Site Number : 8400001
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Site Number : 8400002
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Site Number : 8400004

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

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).
• Any major surgery within the preceding 2 weeks of the first study intervention administration.
• Previous enrollment in this study or current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
• Poor renal function
• Poor hepatic function
• Poor bone marrow function

Cohort C: mPAC

- Any previous systemic therapy with taxane or gemcitabine (for Cohort C only).

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A metastatic breast cancer (mBC); tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)	Drug: tusamitamab ravtansine; Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion; Other Names: SAR408701
Experimental: Cohort B metastatic pancreatic adenocarcinoma (mPAC); tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)	Drug: tusamitamab ravtansine; Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion; Other Names: SAR408701
Experimental: Cohort C Metastatic pancreatic adenocarcinoma (mPAC); 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; Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion; Other Names: SAR408701; Drug: Gemcitabine; Pharmaceutical form: Lyophilized powder for reconstitution or as a solution for infusion; Route of administration: IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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;; 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS was defined as the time from the date of first tusamitamab ravtansine administration to the date of the first documented disease progression according to RECIST v1.1 or death due to any cause, whichever came first. Disease progression was defined as unequivocal progression of existing non-target lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	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)	DCR was defined as the percentage of participants who achieved confirmed CR, confirmed PR or stable disease (SD) as per RECIST v1.1. 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 <10 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. SD was defined as neither sufficient shrinkage from the baseline study to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum of diameters while on study.	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)	DOR was defined as the time from first documented evidence of confirmed CR or confirmed PR until progressive disease determined per RECIST v1.1 or death from any cause, whichever occurred first. 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 <10 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. Disease progression was defined as unequivocal progression of existing non-target lesions; at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	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)
Number of Participants With Treatment-emergent Anti-therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine	Blood samples were collected for assessing the presence of ATA against tusamitamab ravtansine in plasma. The number of participants with treatment-emergent ATA i.e., either seroconverted (treatment-induced ATAs) or boosted their pre-existing ATA response (treatment-boosted ATAs) during the study are reported.	From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment administration [maximum exposure of treatment: 26.1 weeks (Cohort A), 51.6 weeks (Cohort B), 43.3 weeks (Cohort C)]
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An AE was defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious adverse event was defined as any AE that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via an authorized medicinal product. TEAEs were defined as AEs that developed, worsened, or became serious during the treatment-emergent period (defined as the period from the first study treatment administration to the last study treatment administration + 30 days).	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	Blood samples were collected to determine the abnormalities in hematology/coagulation and clinical chemistry. Abnormality criteria was assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Hematological and coagulation parameters assessed were white blood cells, platelets, neutrophils, lymphocytes, and international normalized ratio. Clinical chemistry parameters assessed were albumin, sodium, potassium, calcium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Only those categories in which at least 1 participant had >2 grade worsening in laboratory abnormalities are reported.	From date of first study treatment administration (Day 1) up to 30 days after the last dose of study treatment, approximately 86.6 weeks
Cohort C: Maximum Concentration Observed After Infusion (Cmax) of Tusamitamab Ravtansine	Blood samples were collected for the measurement of Cmax of tusamitamab ravtansine. Cmax was calculated using non-compartmental method.	Cycle 1: Day 1: Start of infusion, end of infusion, 3, 72, 168, and 336 hours post-start of infusion (cycle duration: 28 days)
Cohort C: Area Under the Plasma Concentration Versus Time Curve Calculated Using the Trapezoidal Method From Time 0 to 14 Days (AUC0-14d) of Tusamitamab Ravtansine	Blood samples were collected for the measurement of AUC0-14d of tusamitamab ravtansine. AUC0-14d was calculated using non-compartmental method.	Cycle 1: Day 1: Start of infusion, end of infusion, 3, 72, 168, and 336 hours post-start of infusion (cycle duration: 28 days)
Cohort C: Total Body Clearance From Plasma (CL) of Gemcitabine	Blood samples were collected for the measurement of CL of gemcitabine. CL was calculated using non-compartmental method.	Cycle 1: Days 1 and 8: Start of infusion, end of infusion, 0.25, 1, 1.5, and 2 hours post-start of infusion (cycle duration: 28 days)
Cohort C: Cmax of Gemcitabine Metabolite (dFdU)	Blood samples were collected for the measurement of Cmax of dFdU. Cmax was calculated using non-compartmental method.	Cycle 1: Days 1 and 8: Start of infusion, end of infusion, 0.25, 1, 1.5, and 2 hours post-start of infusion (cycle duration: 28 days)

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Publications and helpful links

Helpful Links

• ACT16432 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Actual): February 16, 2024
• Study Completion (Actual): January 19, 2025

Study Registration Dates

• First Submitted: December 2, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 11, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; tusamitamab ravtansine
• Other Study ID Numbers: ACT16432; 2020-003096-18 (EudraCT Number); U1111-1244-1644 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No