Non-small cell lung cancer metastatic MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: SAR408701
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: Not assigned
Current Sponsor code: SAR408701
Other descriptive name: SAR408701
Concentration un
Sponsors
Sanofi-Aventis Research and Development
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • 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. ;Secondary Objective: 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 ;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.;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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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.;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) | — |
Countries
Bulgaria, Czechia, Czech Republic, Italy, Korea, Republic of, Portugal, Spain, United States
Contacts
Public ContactCristina Garcia
Sanofi-Produtos Farmacêuticos, Lda
Outcome results
None listed