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: Active, not recruiting
• 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 Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

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
    • Rosario, Santa Fe, 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, 7500921
      • Investigational Site Number : 1520003
    • Santiago, Reg Metropolitana De Santiago, Chile, 8420383
      • Investigational Site Number : 1520001
• Hungary
  • Budapest, Hungary, 1122
    • Investigational Site Number : 3480003
• Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • Investigational Site Number : 4100003
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 03080
      • Investigational Site Number : 4100001
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 06351
      • Investigational Site Number : 4100002
• 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
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Investigational Site Number : 6430001
  • Pushkin, Saint- Petersburg, Russian Federation, 196603
    • Investigational Site Number : 6430004
  • Saint -Petersburg, Russian Federation, 197758
    • Investigational Site Number : 6430002
• 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, Taiwan, 704
    • Investigational Site Number : 1580002
  • Taipei, Taiwan, 11217
    • Investigational Site Number : 1580003
• Turkey
  • Adana, Turkey, 01250
    • Investigational Site Number : 7920003
  • Ankara, Turkey, 06100
    • Investigational Site Number : 7920004
  • Istanbul, Turkey, 34722
    • Investigational Site Number : 7920001
  • Izmir, Turkey
    • 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)- Cohort A, Cohort B, and Cohort C Part 2	Objective Response Rate (ORR) of tusamitamab ravtansine in mBC and tusamitamab ravtansine monotherapy and in combination with gemcitabine in mPAC, defined as the proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.	Baseline up to 6 months after the last patient treated have 2 postbaseline tumor assessments
Incidence of dose-limiting toxicites (DLTs)- Cohort C Part 1	Incidence of dose-limiting toxicites (DLTs) in the 28 Day DLT observation period (Cycle 1)	28 days (Cycle 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0	TEAEs, SAEs and laboratory abnormalities according to NCI CTCAE v5.0.	Baseline up to 90 days after the last study treatment administration
Progression free survival (PFS)	PFS defined as the time from the date of first tusamitamab ravtansine administration to the date of the first documented disease progression or death due to any cause, whichever comes first.	Baseline up to 6 months after the last patient treated have 2 postbaseline tumor assessments
Disease control rate (DCR)	DCR defined as the percentage of participants who have achieved CR, PR or stable disease as per RECIST v1.1.	Baseline up to 6 months after the last patient treated have 2 postbaseline tumor assessments
Duration of Response (DOR)	DOR defined as the time from first documented evidence of CR or PR until progressive disease determined per RECIST v1.1 or death from any cause, whichever occurs first.	Baseline up to 6 months after the last patient treated have 2 postbaseline tumor assessments
Incidence of participants with anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine	Incidence of participants with anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine.	Baseline until one month after last patient last treatment
Maximum concentration observed after infusion (Cmax) of tusamitamab ravtansine	Pharmacokinetic parameter of tusamitamab ravtansine.	After 1st administration at Cycle 1 Day 1 (1 Cycle = 28 days)
Area under the plasma concentration versus time curve from time 0 to 14 days (AUC0-14d)	Pharmacokinetic parameter of tusamitamab ravtansine. AUC0-14d calculated using the trapezoidal method.	After 1st administration at Cycle 1 Day 1 (1 Cycle = 28 days)
Total body clearance (CL)	Pharmacokinetic parameter of gemcitabine.	After 1st administration at Cycle 1 Day 1 (1 Cycle = 28 days)
Maximum concentration observed after infusion (Cmax) of gemcitabine metabolite	Pharmacokinetic parameter of gemcitabine metabolite.	After 1st administration at Cycle 1 Day 1 (1 Cycle = 28 days)

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Estimated): April 16, 2024
• Study Completion (Estimated): October 1, 2024

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 (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Maytansine; Gemcitabine
• 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