We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    ACT16146
Previous Study | Return to List | Next Study

Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) in Combination With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With NSQ NSCLC (CARMEN-LC05) (CARMEN-LC05)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04524689
Recruitment Status : Recruiting
First Posted : August 24, 2020
Last Update Posted : September 10, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

•To assess the tolerability and to determine the recommended doses of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed in the NSQ NSCLC population

Secondary Objectives:

  • To assess the safety and tolerability of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed
  • To assess the antitumor activity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab, and platinum-based chemotherapy, with or without pemetrexed in the NSQ NSCLC population
  • To assess the pharmacokinetics (PK) of tusamitamab ravtansine, pembrolizumab, pemetrexed, cisplatin, and carboplatin, each when given in combination as a doublet (tusamitamab ravtansine + pembrolizumab) or triplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy) or a quadruplet (tusamitamab ravtansine + pembrolizumab + platinum-based chemotherapy + pemetrexed)
  • To assess the immunogenicity of tusamitamab ravtansine in combination with pembrolizumab and tusamitamab ravtansine in combination with pembrolizumab and platinum-based chemotherapy with or without pemetrexed

Condition or disease Intervention/treatment Phase
Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) Drug: SAR408701 (Tusamitamab ravtansine) Drug: Pembrolizumab Drug: Cisplatin Drug: Carboplatin Drug: Pemetrexed Phase 2

Detailed Description:
The expected duration of the study intervention for participants may vary based on progression date; median expected duration of study per participant is estimated 10 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 3 months for end-of-treatment assessments and safety follow-up visit).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Phase 2 Study of Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With CEACAM5 Positive Expression Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Actual Study Start Date : October 26, 2020
Estimated Primary Completion Date : July 21, 2023
Estimated Study Completion Date : August 6, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tusamitamab ravtasine + Pembrolizumab
Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.
Drug: SAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Tusamitamab ravtansine

Drug: Pembrolizumab
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Keytruda

Experimental: Tusamitamab ravtansine + Pembrolizumab + carboplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Carboplatin will be infused over 15 to 60 minutes immediately after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
Drug: SAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Tusamitamab ravtansine

Drug: Pembrolizumab
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Keytruda

Drug: Carboplatin
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Experimental: Tusamitamab ravtansine + Pembrolizumab + cisplatin
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.
Drug: SAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Tusamitamab ravtansine

Drug: Pembrolizumab
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Keytruda

Drug: Cisplatin
Pharmaceutical form: Lyophilized powder for reconstitution in solution Route of administration: Intravenous

Experimental: Tusamitamab ravtansine + Pembrolizumab + carboplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
Drug: SAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Tusamitamab ravtansine

Drug: Pembrolizumab
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Keytruda

Drug: Carboplatin
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Drug: Pemetrexed
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

Experimental: Tusamitamab ravtansine + Pembrolizumab + cisplatin + pemetrexed
Pembrolizumab dose will be administered intravenously prior to intravenous adminstration of tusamitamab ravtansine dose every 3 weeks. Pemetrexed will be infused over 10 minutes after tusamitamab ravtansine infusion on Day 1 and then Q3W. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.
Drug: SAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Other Name: Tusamitamab ravtansine

Drug: Cisplatin
Pharmaceutical form: Lyophilized powder for reconstitution in solution Route of administration: Intravenous

Drug: Pemetrexed
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous




Primary Outcome Measures :
  1. Drug-related dose-limiting toxicity (DLTs) [ Time Frame: Baseline up to 10 months after last participant treated ]
    Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity. Each cycle is 21 days.


Secondary Outcome Measures :
  1. Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities [ Time Frame: Baseline up to 10 months after last participant treated ]
    TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 -

  2. Objective response rate (ORR) of tusamitamab ravtansine + pembrolizumab + platinum based chemotherapy, with or without pemetrexed [ Time Frame: Baseline up to 10 months after last participant treated ]
    ORR is defined as 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)

  3. Incidence of anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine [ Time Frame: At cycle 1, 2, 3, 4,6, 8 then every 5 cycles and end of treatment. Each cycle is 21 days. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations.
  • No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease).
  • Expression of CEACAM5 as demonstrated prospectively by a centrally assessed Immunohistochemistry (IHC) assay of ≥2+ in intensity involving at least 1% of the tumor cell population in archival tumor sample (or if not available fresh biopsy sample).
  • Measurable disease based on RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
  • Capable of giving signed informed consent

Exclusion criteria:

  • Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CTP3A inhibitor.
  • Uncontrolled brain metastases and history of leptomeningeal disease.
  • Significant concomitant illness, including any severe medical condition that, in the opinion of the investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results.
  • 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 HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection.
  • History of active autoimmune disease that has required systemic treatment in the past 2 years.
  • History of allogeneic tissue/solid organ transplantation.
  • Active infection requiring IV systemic therapy within 2 weeks prior to randomization or active tuberculosis.
  • Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
  • 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.
  • Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted.
  • Symptomatic herpes zoster within 3 months prior to screening.
  • Significant allergies to humanized monoclonal antibodies.
  • Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
  • Concurrent treatment with any other anticancer therapy.
  • Have received prior chemotherapy treatment for advanced/metastatic NSCLC.
  • The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation
  • 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 any investigational treatment).
  • Any prior therapy targeting CEACAM5.
  • Any prior treatment with any other anti-PD-1, or PD-L1 or programmed death ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4.
  • Any prior maytansinoid treatment (DM1 or DM4 ADC).
  • Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication. Daily steroid replacement therapy or any corticosteroid premedication if applicable are allowed.
  • Any radiation therapy to lung >30 Gy within 6 months of first study intervention administration.
  • Has received or will receive a live vaccine within 30 days prior to the first study intervention administration.
  • Any major surgery within the preceding 3 weeks of the first study intervention administration.

Prior/concurrent clinical study experience

  • Current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
  • Poor organ function

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04524689


Contacts
Layout table for location contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
Show Show 27 study locations
Sponsors and Collaborators
Sanofi
Investigators
Layout table for investigator information
Study Director: Clinical Sciences & Operations Sanofi
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04524689    
Other Study ID Numbers: ACT16146
U1111-1233-9798 ( Registry Identifier: ICTRP )
First Posted: August 24, 2020    Key Record Dates
Last Update Posted: September 10, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Cisplatin
Carboplatin
Pembrolizumab
Pemetrexed
Maytansine
Antineoplastic Agents
Antineoplastic Agents, Immunological
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators