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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04524689




Registration number
NCT04524689
Ethics application status
Date submitted
20/08/2020
Date registered
24/08/2020
Date last updated
17/03/2025

Titles & IDs
Public title
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
Scientific 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)
Secondary ID [1] 0 0
U1111-1233-9798
Secondary ID [2] 0 0
ACT16146
Universal Trial Number (UTN)
Trial acronym
CARMEN-LC05
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SAR408701 (Tusamitamab ravtansine)
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Drugs - Pemetrexed

Experimental: Tusamitamab ravtasine 150 mg/m^2 + Pembrolizumab - Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Experimental: Tusamitamab ravtasine 170 mg/m^2 + Pembrolizumab - Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Experimental: Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or cisplatin - 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. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.

Experimental: Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or cisplatin - 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. Cisplatin will be infused approximately 30 minutes after tusamitamab ravtansine infusion on Day 1 and Q3W for the first 4 cycles.

Experimental: Tusamitamab ravtansine 150 mg/m^2 + Pembrolizumab + carboplatin or 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. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.

Experimental: Tusamitamab ravtansine 170 mg/m^2 + Pembrolizumab + carboplatin or 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. Carboplatin will be infused over 15 to 60 minutes immediately after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles. Cisplatin will be infused approximately 30 minutes after pemetrexed infusion after pemetrexed infusion on Day 1 and Q3W for the first 4 cycles.


Treatment: Drugs: SAR408701 (Tusamitamab ravtansine)
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous

Treatment: Drugs: Pembrolizumab
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous

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

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

Treatment: Drugs: Pemetrexed
Pharmaceutical form: Concentrate for solution for infusion Route of administration: Intravenous
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
All Cohorts: Number of Participants With Study Drug-Related Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1 Day 1 up to Cycle 1 Day 21 (cycle duration=3 weeks)
Primary outcome [2] 0 0
Doublet Cohort: Objective Response Rate (ORR)
Timepoint [2] 0 0
Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 155.4 weeks
Primary outcome [3] 0 0
Quadruplet Cohort: Objective Response Rate
Timepoint [3] 0 0
Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 108.4 weeks
Secondary outcome [1] 0 0
All Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Timepoint [1] 0 0
From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 159.4 weeks (doublet), 117 weeks (triplet), and 112.4 weeks (quadruplet)
Secondary outcome [2] 0 0
Doublet and Quadruplet Cohorts: Progression-free Survival (PFS)
Timepoint [2] 0 0
Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 155.4 weeks (doublet) and 108.4 weeks (quadruplet)
Secondary outcome [3] 0 0
All Cohorts: Disease Control Rate (DCR)
Timepoint [3] 0 0
Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 155.4 weeks (doublet), 113 weeks (triplet), and 108.4 weeks (quadruplet)
Secondary outcome [4] 0 0
All Cohorts: Duration of Response (DOR)
Timepoint [4] 0 0
Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 155.4 weeks (doublet), 113 weeks (triplet), and 108.4 weeks (quadruplet)
Secondary outcome [5] 0 0
Triplet Cohort: Objective Response Rate
Timepoint [5] 0 0
Tumor assessments performed at baseline, then every 6 weeks for first 24 weeks, and every 9 weeks thereafter, approximately 113 weeks
Secondary outcome [6] 0 0
All Cohorts: Trough Concentration (Ctrough) of Tusamitamab Ravtansine
Timepoint [6] 0 0
Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks)
Secondary outcome [7] 0 0
All Cohorts: Ctrough of Pembrolizumab
Timepoint [7] 0 0
Pre-dose on Day 1 of Cycle 2 (cycle duration=3 weeks)
Secondary outcome [8] 0 0
Quadruplet Cohort: Plasma Concentration of Pemetrexed
Timepoint [8] 0 0
30 minutes post-dose on Day 1 of Cycle 1 (cycle duration=3 weeks)
Secondary outcome [9] 0 0
Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion (Ceoi) of Cisplatin
Timepoint [9] 0 0
At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks)
Secondary outcome [10] 0 0
Triplet and Quadruplet Cohorts: Total Plasma Concentration Observed at the End of Infusion of Carboplatin
Timepoint [10] 0 0
At end of infusion on Day 1 of Cycle 1 (cycle duration=3 weeks)
Secondary outcome [11] 0 0
All Cohorts: Number of Participants With Treatment-emergent Anti-Therapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine
Timepoint [11] 0 0
From first dose of study treatment (Day 1) up to 30 days post last dose of study treatment, approximately 159.4 weeks (doublet), 117 weeks (triplet), and 112.4 weeks (quadruplet)

Eligibility
Key inclusion 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
* Life expectancy of at least 3 months
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Medical condition requiring concomitant administration of a medication with a strong CYP3A 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/12/2024
Sample size
Target
Accrual to date
Final
57
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kansas
Country [2] 0 0
Brazil
State/province [2] 0 0
Rio Grande Do Norte
Country [3] 0 0
Chile
State/province [3] 0 0
La Araucanía
Country [4] 0 0
Chile
State/province [4] 0 0
Valparaíso
Country [5] 0 0
Chile
State/province [5] 0 0
Santiago
Country [6] 0 0
Czechia
State/province [6] 0 0
Olomouc
Country [7] 0 0
Czechia
State/province [7] 0 0
Ostrava - Vitkovice
Country [8] 0 0
France
State/province [8] 0 0
Avignon
Country [9] 0 0
France
State/province [9] 0 0
Brest
Country [10] 0 0
France
State/province [10] 0 0
Pessac
Country [11] 0 0
France
State/province [11] 0 0
Poitiers Cedex
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Hungary
State/province [13] 0 0
Farkasgyepü
Country [14] 0 0
Israel
State/province [14] 0 0
Ramat Gan
Country [15] 0 0
Israel
State/province [15] 0 0
Tel Aviv
Country [16] 0 0
Spain
State/province [16] 0 0
A Coruña [La Coruña]
Country [17] 0 0
Spain
State/province [17] 0 0
Asturias
Country [18] 0 0
Spain
State/province [18] 0 0
Catalunya [Cataluña]
Country [19] 0 0
Spain
State/province [19] 0 0
Las Palmas
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Trial Transparency email recommended (Toll free number for US & Canada)
Address 0 0
Country 0 0
Phone 0 0
800-633-1610
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT04524689