Clinical Trials Register

Summary
EudraCT Number:	2020-000035-50
Sponsor's Protocol Code Number:	ACT16146
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-04-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2020-000035-50

A.3

Full title of the trial

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)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

SAR408701 in combination with pembrolizumab and pembrolizumab alone in patients with non-squamous non-small cell lung cancer (NSQ NSCLC)

A.3.2

Name or abbreviated title of the trial where available

CARMEN-LC05

A.4.1

Sponsor's protocol code number

ACT16146

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1233-9798

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi aventis recherche & développement
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi-Aventis Recherche & Développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi-aventis France
B.5.2	Functional name of contact point	Direction des Opérations Cliniques
B.5.3	Address:
B.5.3.1	Street Address	1 avenue Pierre Brossolette
B.5.3.2	Town/ city	Chilly-Mazarin
B.5.3.3	Post code	91385
B.5.3.4	Country	France
B.5.4	Telephone number	0 8000 222 55
B.5.6	E-mail	Public-Registry-MA-France@sanofi.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	SAR408701
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not assigned
D.3.9.2	Current sponsor code	SAR408701
D.3.9.3	Other descriptive name	SAR408701
D.3.9.4	EV Substance Code	SUB130908
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Anti-CEACAM 5 antibody maytansine conjugate.
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Keytruda
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Pembrolizumab
D.3.9.1	CAS number	1374853-91-4
D.3.9.4	EV Substance Code	SUB167136
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Non-squamous non–small-cell lung cancer (NSQ NSCLC)

E.1.1.1

Medical condition in easily understood language

Cancer

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10079440
E.1.2	Term	Non-squamous non-small cell lung cancer
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

• To assess the safety and tolerability of SAR408701 in combination with pembrolizumab and pembrolizumab single agent
• 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 and pembrolizumab when given in combination, and of pembrolizumab when given as a single agent
• To assess the immunogenicity of SAR408701 when given in combination with pembrolizumab

E.2.3

Trial contains a sub-study

E.3

Principal 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 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).
- 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

E.4

Principal exclusion criteria

- Medical condition reauiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or astrong 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 longer, 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

E.5 End points

E.5.1

Primary end point(s)

Part 1: Number of partcipants 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

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)

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1 and Part 2 : Baseline up to 10 months after last participant treated

E.5.2

Secondary end point(s)

1. 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

2. 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

3. Progression-free surviva - 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

4. 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

5. Cmax of SAR408701 and pembrolizumab - Maximum concentration observed after infusion (Cmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone

6. Tmax of SAR408701 and pembrolizumab - Time to reach Cmax (Tmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone

7. Clast of SAR408701 and pembrolizumab - Last 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

8. Tlast of SAR408701 and pembrolizumab - Time of Clast (Tlast) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone

E.5.2.1

Timepoint(s) of evaluation of this end point

1. to 8. : Baseline up to 10 months after last participant treated

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

Yes

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Czech Republic

France

Hungary

Israel

Spain

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-08-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-07

P. End of Trial
P.	End of Trial Status	Ongoing

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