Clinical Trials Register

Summary
EudraCT Number:	2019-003914-15
Sponsor's Protocol Code Number:	ACT16525
National Competent Authority:	Portugal - INFARMED
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-03-25
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Portugal - INFARMED

A.2

EudraCT number

2019-003914-15

A.3

Full title of the trial

Open-label, single-arm trial to evaluate antitumor activity, safety, and pharmacokinetics of SAR408701 used in combination with ramucirumab in metastatic, non-squamous, non–small-cell lung cancer (NSQ NSCLC) patients with CEACAM5-positive tumors, previously treated with platinum-based chemotherapy and an immune checkpoint inhibitor

A.3.1

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

SAR408701 in combination with ramucirumab in pre-treated patients with non squamous non-small cell lung cancer (NSQ NSCLC)

A.3.2

Name or abbreviated title of the trial where available

CARMEN-LC04

A.4.1

Sponsor's protocol code number

ACT16525

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1244-1585

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 Research and Development
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-Produtos Farmacêuticos, Lda
B.5.2	Functional name of contact point	Cristina Garcia
B.5.3	Address:
B.5.3.1	Street Address	Empreendimento Lagoas Park, Ed. 7, 3º piso
B.5.3.2	Town/ city	Porto Salvo
B.5.3.3	Post code	2740-244
B.5.3.4	Country	Portugal
B.5.4	Telephone number	0034600932546
B.5.5	Fax number	0034934895762
B.5.6	E-mail	es-reg-estudiosclinicos@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.3.1	Product name	SAR408701
D.3.4	Pharmaceutical form	Concentrate for solution for injection
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	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	Yes
D.2.1.1.1	Trade name	CYRAMZA
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland 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 injection
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	CYRAMZA
D.3.9.1	CAS number	947687-13-0
D.3.9.3	Other descriptive name	RAMUCIRUMAB
D.3.9.4	EV Substance Code	SUB32795
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	10
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-small cell lung cancer metastatic

E.1.1.1

Medical condition in easily understood language

Non-small cell lung cancer metastatic

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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10059515
E.1.2	Term	Non-small cell lung cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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 ramucirumab in the NSQ NSCLC population.
• Part 2:
To assess the antitumor activity of SAR408701 in combination with ramucirumab in the NSQ NSCLC population.

E.2.2

Secondary objectives of the trial

To assess the safety and tolerability of SAR408701 in combination with ramucirumab
To assess the durability of the response to treatment with SAR408701 in combination with ramucirumab
To assess efficacy of SAR408701 in combination with ramucirumab on progression free survival
To assess the pharmacokinetic (PK) profile of SAR408701 and ramucirumab when given in combination
To assess the immunogenicity of SAR408701 when given in combination with ramucirumab

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Metastatic disease progression fulfilling both of the following 2 criteria:
a) Having progressive disease during or after platinum-based chemotherapy (at least 2 cycles). Maintenance therapy following platinum-based chemotherapy is not considered as a separate regimen. Adjuvant/neoadjuvant treatment for a patient who had a relapse with metastatic disease during or within 6 months of completing treatment will be considered as first-line treatment.
AND
b) Having progressive disease during or after 1 immune checkpoint inhibitor (anti-PD1/PD-L1); this could be given as monotherapy or in combination with platinum-based chemotherapy (whatever the order).

• Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5 expression of ≥2+ in archival tumor sample (or if not available, fresh biopsy sample) involving at least 50 % of the tumor cell population as demonstrated prospectively by central laboratory via immune histochemistry (IHC).
• At least one measurable lesion by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• A female participant who agrees to use effective contraceptive methods during and for at least 7 months after the last dose of study intervention.
• A male participant who agrees to use effective contraception methods during and for at least 4 months after the last dose of study intervention
• Signed informed consent

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
• Patients with untreated brain metastases and history of leptomeningeal disease.
• Significant concomitant illnesses that 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.
• Non-resolution of any prior treatment related toxicity to < grade 2 according to NCI CTCAE V5.0, except for alopecia, vitiligo and active thyroiditis controlled with hormonal replacement therapy
• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis
• Previous history of and/or unresolved corneal disorders. The use of contact lenses is not permitted.
• Radiographic evidence of major airway or blood vessel invasion or intratumor cavitation
• History of uncontrolled hereditary or acquired thrombotic disorder or history of aneurism.
• Major surgery within 28 days prior to Day 1/first IMP infusion,. Postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months.
• History of gross hemoptysis within 2 months before the first administration of study intervention.
• Clinically relevant congestive heart failure (CHF; NYHA II-IV or LVEF less than 50%) or symptomatic or poorly controlled cardiac arrhythmia.
• Any arterial thrombotic event within 6 months before the first administration of study intervention.
• Uncontrolled arterial hypertension (systolic ≥150 mmHg or diastolic ≥90 mmHg) despite standard medical management.
• Serious or nonhealing wound, skin ulcer, or bone fracture within 28 days before the first administration of study intervention.
• Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first administration of study intervention.
• Significant bleeding disorders, vasculitis, or Grade 3-4 gastrointestinal (GI) bleeding within 3 months before the first administration of study intervention.
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection Crohn's disease, ulcerative colitis, or chronic diarrhea.
• Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CYP3A inhibitor
• Concurrent treatment with any other anticancer therapy
• No more than 1-line previous chemotherapy in metastatic setting
• Prior treatment with ramucirumab or docetaxel
• Prior therapy targeting CEACAM5 or maytansinoid treatment (DM1 or DM4 antibody-drug conjugate)
• Contraindication to use of corticosteroid premedication
• Current therapeutic anticoagulation with warfarin, low-molecular-weight heparin, or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible
• Previous enrollment in this study, current participation in any other clinical study involving an investigational study treatment, or any other type of medical research
• Poor bone marrow, liver or kidney functions
• Urine dipstick or routine analysis indicating proteinuria of 2+ or higher, unless a 24 hour urine collection demonstrates <1000 mg of protein.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.Most important exclusion criteria for potential participants

E.5 End points

E.5.1

Primary end point(s)

Part 1: Incidence of study drug-related dose-limiting toxicity (DLT) at Cycle 1 and Cycle 2 - Drug-related dose-limiting toxicity (DLT) as observed during DLT-observation period tolerability in order to confirm the recommended dose of SAR408701 in combination with ramucirumab for the Part 2.

Part 2: Objective response rate - Objective response rate defined as proportion of participants with confirmed complete response (CR) or partial response (PR) as best overall response determined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

E.5.1.1

Timepoint(s) of evaluation of this end point

Part 1. - baseline up to Cycle 2 (approximatively 1 month)
Part 2. - Baseline up to 6 months after the last patient treated

E.5.2

Secondary end point(s)

1. Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) - Incidence of TEAEs and SAEs and laboratory abnormalities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5.0.

2. Duration of response (DOR) - Duration of response (DOR) is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST v.1.1 or death from any cause, whichever occurs first.

3. Progression-free survival (PFS) - Progression-free survival (PFS) is defined as the time from the first investigational medicinal product (IMP) administration to the date of the first documented disease progression or death due to any cause, whichever comes first.

4.
a)PK - Cmax of SAR408701 - Cmax Maximum concentration of SAR408701 observed after SAR408701 1st infusion
b)PK - AUC0-14d of SAR408701 - AUC0-14d Area under the plasma SAR408701 concentration versus time curve calculated using the trapezoidal method from time 0 to 14 days after SAR408701 1st infusion.
c)PK - Cthrough of SAR408701 - Ctrough Concentration observed of SAR408701 just before SAR408701 treatment administration during repeated dosing
d)Cthrough of ramucirumab - Ctrough Concentration observed of ramucirumab just before ramucirumab treatment administration during repeated dosing

5. Incidence of anti-therapeutic antibodies (ATAs) against SAR408701 - Incidence of anti-therapeutic antibodies (ATAs) against SAR408701.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. Baseline up to 90 days after the last study treatment administration
2. Baseline up to 6 months after the last patient treated
3. Baseline up to 6 months after the last patient treated
4. a) and b) Cycle 1 (each cycle = 2 weeks)
4. c) Baseline up to cycle 13 (each cycle= 2 weeks)
4. d) Baseline to cycle 7 (each cycle= 2 weeks)
5. Baseline up to end of treatment (approximately 6 months)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

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

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

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)

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

Korea, Republic of

United States

Bulgaria

Italy

Portugal

Spain

Czechia

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

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.4.2.1

In the EEA

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

2020-07-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-06-15

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials