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SAR408701 in Combination With Ramucirumab in Pre-treated Patients With Non Squamous Non-small Cell Lung Cancer (NSQ NSCLC) (CARMEN-LC04)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04394624
Recruitment Status : Recruiting
First Posted : May 19, 2020
Last Update Posted : November 9, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objectives:

o 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.

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

Secondary Objectives:

  • 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

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Metastatic Drug: SAR408701 Drug: ramucirumab Phase 2

Detailed Description:
The expected duration of the study intervention for participants may vary, based on progression date ; median expected duration of study per participant is estimated 11 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 4 months for end-of-treatment assessments and safety follow-up visit)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 3, 2020
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Ramucirumab

Arm Intervention/treatment
Experimental: Ramucirumab + SAR408701
Ramucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks.
Drug: SAR408701
Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion

Drug: ramucirumab
Pharmaceutical form:concentrate for solution for injection Route of administration: intravenous infusion




Primary Outcome Measures :
  1. Part 1: Incidence of study drug-related dose-limiting toxicity (DLT) at Cycle 1 and Cycle 2 [ Time Frame: baseline up to Cycle 2 (approximatively 1 month) ]
    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.

  2. Part 2: Objective response rate [ Time Frame: Baseline up to 6 months after the last patient treated ]
    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.


Secondary Outcome Measures :
  1. Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Baseline up to 90 days after the last study treatment administration ]
    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) [ Time Frame: Baseline up to 6 months after the last patient treated ]
    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) [ Time Frame: Baseline up to 6 months after the last patient treated ]
    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. PK - Cmax of SAR408701 [ Time Frame: Cycle 1 (each cycle = 2 weeks) ]
    Maximum concentration (Cmax) of SAR408701 observed after SAR408701 1st infusion.

  5. PK - AUC0-14d of SAR408701 [ Time Frame: Cycle 1 (each cycle=2 weeks) ]
    Area under the plasma SAR408701 concentration versus time curve calculated using the trapezoidal method from time 0 to 14 days (AUC0-14d) after SAR408701 1st infusion.

  6. PK - Ctrough of SAR408701 [ Time Frame: Baseline up to cycle 13 (each cycle= 2 weeks) ]
    Concentration observed of SAR408701 just before SAR408701 treatment administration during repeated dosing.

  7. Ctrough of ramucirumab [ Time Frame: Baseline to cycle 7 (each cycle= 2 weeks) ]
    Concentration observed of ramucirumab just before ramucirumab treatment administration during repeated dosing.

  8. Incidence of anti-therapeutic antibodies (ATAs) against SAR408701 [ Time Frame: Baseline up to end of treatment (approximately 6 months) ]
    Incidence of anti-therapeutic antibodies (ATAs) against SAR408701.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Histologically or cytologically proven diagnosis of non-squamous NSCLC with metastatic disease progression

    1. After one prior line of chemotherapy in a metastatic setting. Development of metastatic disease during or within 6 months of an adjuvant/neoadjuvant treatment (to be considered as first-line treatment).
    2. After or during one platinum-based chemotherapy and one immune checkpoint inhibitor (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

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; New York Heart Association [NYHA] II-IV) 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

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394624


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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Bulgaria
Investigational Site Number 1000001 Recruiting
Plovdiv, Bulgaria, 4004
Investigational Site Number 1000002 Recruiting
Sofia, Bulgaria, 1431
Korea, Republic of
Investigational Site Number 4100001 Recruiting
Seoul, Korea, Republic of, 03080
Investigational Site Number 4100002 Recruiting
Seoul, Korea, Republic of, 03722
Portugal
Investigational Site Number 6200001 Recruiting
Porto, Portugal, 4200-162
Spain
Investigational Site Number 7240001 Recruiting
Barcelona / Sabadell, Spain, 08208
Investigational Site Number 7240004 Recruiting
Madrid, Spain, 28040
Investigational Site Number 7240005 Recruiting
Madrid, Spain, 28046
Investigational Site Number 7240002 Recruiting
Valencia, Spain, 46014
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT04394624    
Other Study ID Numbers: ACT16525
2019-003914-15 ( EudraCT Number )
U1111-1244-1585 ( Other Identifier: UTN )
First Posted: May 19, 2020    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Ramucirumab
Antineoplastic Agents