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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04524689




Registration number
NCT04524689
Ethics application status
Date submitted
20/08/2020
Date registered
24/08/2020
Date last updated
19/10/2023

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 (CARMEN-LC05)
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 + Pembrolizumab - Pembrolizumab dose will be administered intravenously prior to intravenous administration of tusamitamab ravtansine dose every 3 weeks.

Experimental: Tusamitamab ravtansine + 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 + 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
Incidence of study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21)
Timepoint [1] 0 0
Baseline up to 21 days
Primary outcome [2] 0 0
Expansion part (including participants treated at the recommended dose for expansion [RDE] from the Safety Run-in part): Objective response rate (ORR)
Timepoint [2] 0 0
Baseline up to approximately 4.5 months after last participant first treated
Secondary outcome [1] 0 0
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities according to Common Terminology Criteria for Adverse Events (CTCAE) V5.0
Timepoint [1] 0 0
Baseline up to 30 days after last IMP administration
Secondary outcome [2] 0 0
Progression-free survival (PFS)
Timepoint [2] 0 0
Baseline up to 10.5 months after first IMP administration of the last participant
Secondary outcome [3] 0 0
Disease control rate (DCR)
Timepoint [3] 0 0
Baseline up to 4.5 months after first IMP administration of the last participant
Secondary outcome [4] 0 0
Duration of response (DOR)
Timepoint [4] 0 0
Baseline up to 10.5 months after first IMP administration of the last participant
Secondary outcome [5] 0 0
ORR
Timepoint [5] 0 0
Baseline up to 4.5 months after first IMP administration of the last participant
Secondary outcome [6] 0 0
Pharmacokinetic concentrations
Timepoint [6] 0 0
PK concentrations assessed at multiple timepoints up to C13 for tusamitamab ravtansine, up to cycle 8 for pembrolizumab, up to cycle 1 for cisplatin, carboplatin and pemetrexed
Secondary outcome [7] 0 0
Incidence of anti-therapeutic antibodies (ATAs) against tusamitamab ravtansine
Timepoint [7] 0 0
At cycle 1, 2, 3, 4,6, 8 then every 5 cycles and end of treatment. Each cycle is 21 days

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
Recruiting
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
25/04/2025
Actual
Sample size
Target
215
Accrual to date
Final
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
United States of America
State/province [2] 0 0
Texas
Country [3] 0 0
United States of America
State/province [3] 0 0
Virginia
Country [4] 0 0
Chile
State/province [4] 0 0
La Araucanía
Country [5] 0 0
Chile
State/province [5] 0 0
Valparaíso
Country [6] 0 0
Chile
State/province [6] 0 0
Santiago
Country [7] 0 0
Czechia
State/province [7] 0 0
Olomouc
Country [8] 0 0
Czechia
State/province [8] 0 0
Ostrava - Vitkovice
Country [9] 0 0
France
State/province [9] 0 0
Avignon
Country [10] 0 0
France
State/province [10] 0 0
Brest
Country [11] 0 0
France
State/province [11] 0 0
Pessac
Country [12] 0 0
France
State/province [12] 0 0
Poitiers Cedex
Country [13] 0 0
Hungary
State/province [13] 0 0
Budapest
Country [14] 0 0
Hungary
State/province [14] 0 0
Farkasgyepü
Country [15] 0 0
Hungary
State/province [15] 0 0
Kaposvár
Country [16] 0 0
Hungary
State/province [16] 0 0
Kecskemét
Country [17] 0 0
Hungary
State/province [17] 0 0
Nyíregyháza
Country [18] 0 0
Israel
State/province [18] 0 0
Jerusalem
Country [19] 0 0
Israel
State/province [19] 0 0
Ramat Gan
Country [20] 0 0
Israel
State/province [20] 0 0
Tel Aviv
Country [21] 0 0
Spain
State/province [21] 0 0
Valenciana, Comunidad
Country [22] 0 0
Spain
State/province [22] 0 0
La Coruña
Country [23] 0 0
Spain
State/province [23] 0 0
Las Palmas
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objective:

- Safety run-in part: 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 to be tested in the expansion part of the study in the NSQ NSCLC population

- Expansion part (including participants treated at the recommended dose for expansion
[RDE] from the Safety Run-in part): to assess the antitumor activity of several dose
levels (DLs; if applicable) of tusamitamab ravtansine in combination with pembrolizumab
and of several DLs of tusamitamab ravtansine in combination with pembrolizumab,
platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population

Secondary Objectives:

- To assess the safety and tolerability of several DLs (if applicable) of tusamitamab
ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in
combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of
tusamitamab ravtansine in combination with pembrolizumab, and platinum-based
chemotherapy with pemetrexed in the NSQ NSCLC population

- To assess the antitumor activity of several DLs (if applicable) of tusamitamab
ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab ravtansine in
combination with pembrolizumab and platinum-based chemotherapy, and of several DLs of
tusamitamab ravtansine in combination with pembrolizumab, platinum-based chemotherapy,
and pemetrexed in the NSQ NSCLC population

- To assess the durability of the response to treatment with several DLs (if applicable)
of tusamitamab ravtansine in combination with pembrolizumab and of 1 DL of tusamitamab
ravtansine in combination with pembrolizumab and platinum-based chemotherapy, and of
several DLs of tusamitamab ravtansine in combination with pembrolizumab and
platinum-based chemotherapy, and pemetrexed in the NSQ NSCLC population

- To assess the antitumor activity of tusamitamab ravtansine in combination with
pembrolizumab and platinum-based chemotherapy 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 a 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
Trial website
https://clinicaltrials.gov/ct2/show/NCT04524689
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04524689