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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04524689
Ethics application status
Date submitted
20/08/2020
Date registered
24/08/2020
Date last updated
14/04/2021

Titles & IDs
Public title
SAR408701 in Combination With Pembrolizumab and Pembrolizumab Alone in Patients With Non-squamous Non-small Cell Lung Cancer (NSQ NSCLC)
Scientific title
Randomized, Open-label, Phase 2 Study of SAR408701 Combined With Pembrolizumab and Pembrolizumab Alone in Patients With CEACAM5 and PD-L1 Positive 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
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin

Experimental: SAR408701 + Pembrolizumab - Pembrolizumab will be administered intravenously prior to intravenously adminstration of SAR408701 every 3 weeks

Active Comparator: Pembrolizumab - Pembrolizumab - Pembrolizumab will be administered intravenously every 3 weeks. - Type:

Experimental: SAR408701 + Pembrolizumab + cisplatin - Pembrolizumab will be administered intravenously prior to intravenously administration of SAR408701 every 3 weeks. Cisplatin should be infused approximately 30 minutes after SAR408701 infusion on Day 1 and then Q3W for the first 4 cycles.

Experimental: SAR408701 + Pembrolizumab + carboplatin - Pembrolizumab will be administered intravenously prior to intravenously administration of SAR408701 every 3 weeks. Carboplatin will be administered as an IV infusion over 15 to 60 minutes as per local practice and labels immediately after SAR408701 infusion on Day 1 and Q3W for the first 4 cycles


Treatment: Drugs: SAR408701
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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A Part 1 and Part B: Number of participants with study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21) - Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity
Timepoint [1] 0 0
Baseline up to 10 months after last participant treated
Primary outcome [2] 0 0
Part A Part 2: Objective response rate (ORR) of SAR408701 + pembrolizumab and pembrolizumab single agent - - 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)
Timepoint [2] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [1] 0 0
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities - TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 -
Timepoint [1] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [2] 0 0
Part A: Duration of response - Duration of response (DOR), defined as the time from first documented evidence of CR or PR until progressive disease determined per RECIST 1.1 or death from any cause, whichever occurs first
Timepoint [2] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [3] 0 0
Part A: Progression-free survival - Progression-free survival, defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever comes first
Timepoint [3] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [4] 0 0
Ceoi of SAR408701 and pembrolizumab - Concentration observed at the end of IV infusion (Ceoi) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Timepoint [4] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [5] 0 0
Cmax of SAR408701, pembrolizumab, Cisplatin, and carboplatin - Maximum concentration observed after infusion (Cmax) of SAR408701, pembrolizumab, cisplatin and carboplatin when given in combination and of pembrolizumab when given alone
Timepoint [5] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [6] 0 0
Tmax of SAR408701, pembrolizumab, cisplatin and carboplatin - Time to reach Cmax (Tmax) of SAR408701, pembrolizumab, cisplatin and carboplatin when given in combination and of pembrolizumab when given alone
Timepoint [6] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [7] 0 0
Clast of SAR408701 and pembrolizumab - Clast concentration observed above the lower limit of quantification after infusion (Clast)of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Timepoint [7] 0 0
Baseline up to 10 months after last participant treated -
Secondary outcome [8] 0 0
Tlast of SAR408701 and pembrolizumab - Time of Clast (Tlast) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Timepoint [8] 0 0
Baseline up to 10 months after last participant treated -
Secondary outcome [9] 0 0
Ctrough of SAR408701 and pembrolizumab - Concentration observed just before treatment administration during repeated dosing (Ctrough) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Timepoint [9] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [10] 0 0
AUC0-21d of SAR408701 and pembrolizumab - Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to 21 days (AUC 0-21d) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Timepoint [10] 0 0
Baseline up to 10 months after last participant treated - 11. Baseline up to end of study (approximately 2 years) -
Secondary outcome [11] 0 0
Incidence of anti-therapeutic antibodies (ATAs) against SAR408701 - Incidence of anti-therapeutic antibodies (ATAs) against SAR408701
Timepoint [11] 0 0
Baseline up to end of study (approximately 2 years)
Secondary outcome [12] 0 0
Part B: Objective response rate (ORR) of SAR408701 + pembrolizumab + platinum based chemotherapy - ORR is defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per RECIST v1.1
Timepoint [12] 0 0
Baseline up to 10 months after last participant treated
Secondary outcome [13] 0 0
AUC0-72h of cisplatin or carboplatin - Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to 72 hours of cisplatin or carboplatin when given in combination
Timepoint [13] 0 0
Baseline up to 10 months after last participant treated

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 50% of the
tumor cell population in archival tumor sample (or if not available fresh biopsy
sample).

- For participants enrolled to Part A, PD-L1 positive tumor (TPS =1%) as determined
locally by an approved test

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- Medical condition requiring concomitant administration of a medication with a narrow
therapeutic window and metabolized by CYP450 or a strong CTP3A inhibitor.

- Untreated 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
Randomised controlled 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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 0360001 - Heidelberg West
Recruitment hospital [2] 0 0
Investigational Site Number 0360003 - Macquarie Park
Recruitment postcode(s) [1] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [2] 0 0
2109 - Macquarie Park
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
Chile
State/province [3] 0 0
Santiago
Country [4] 0 0
Chile
State/province [4] 0 0
Viña Del Mar
Country [5] 0 0
France
State/province [5] 0 0
Brest
Country [6] 0 0
France
State/province [6] 0 0
Pessac
Country [7] 0 0
France
State/province [7] 0 0
Poitiers Cedex
Country [8] 0 0
Hungary
State/province [8] 0 0
Budapest
Country [9] 0 0
Hungary
State/province [9] 0 0
Budatest
Country [10] 0 0
Hungary
State/province [10] 0 0
Debrecen
Country [11] 0 0
Hungary
State/province [11] 0 0
Farkasgyepü
Country [12] 0 0
Israel
State/province [12] 0 0
Jerusalem
Country [13] 0 0
Spain
State/province [13] 0 0
Las Palmas
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
Spain
State/province [15] 0 0
Valencia / Valencia

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

Ethics approval
Ethics application status

Summary
Brief summary
Primary Objectives:

- Part A - Part 1 (safety run-in): To assess the tolerability and to confirm the
recommended dose of SAR408701 in combination with pembrolizumab in the NSQ NSCLC
population

- Part A - Part 2: To assess the antitumor activity of SAR408701 in combination with
pembrolizumab and pembrolizumab single agent in the NSQ NSCLC population

- Part B: To assess the tolerability and to determine the recommended dose of SAR408701 in
combination with pembrolizumab and platinum-based chemotherapy in the NSQ NSCLC
population

Secondary Objectives:

- To assess the durability of the response to treatment with SAR408701 in combination with
pembrolizumab and pembrolizumab single agent and SAR408701 in combination with
pembrolizumab and platinum-based chemotherapy (Investigator's choice of cisplatin or
carboplatin)

- To assess the durability of the response to treatment with SAR408701 in combination with
pembrolizumab and pembrolizumab single agent

- To assess the efficacy on progression-free survival (PFS) of SAR408701 in combination
with pembrolizumab and pembrolizumab single agent

- To assess the pharmacokinetics (PK) of SAR408701, pembrolizumab, cisplatin, and
carboplatin, each when given in combination as a doublet or a triplet, and of
pembrolizumab when given as a single agent

- To assess the immunogenicity of SAR408701 when given in combination with pembrolizumab
and in combination with pembrolizumab and platinum-based chemotherapy

- To assess the antitumor activity of SAR408701 in combination with pembrolizumab and
platinum-based chemotherapy
Trial website
https://clinicaltrials.gov/show/NCT04524689
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
Contact-US@sanofi.com
Contact person for scientific queries

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