Cancer MedDRA version: 20.1 Level: PT Classification code 10062878 Term: Gastrooesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10001150 Term: Adenocarcinoma gastric System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Tusamitamab ravtansine
Product Code: SAR408701
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Tusamitamab ravtansine
Current Sponsor code: SAR408701
Oth
Sponsors
Sanofi aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically or cytologically confirmed diagnosis of gastric or GEJ adenocarcinoma. • Metastatic disease or locally advanced, unresectable disease. • Participants who have measurable target lesion. • Participants with high carcinoembryonic antigen-related cell adhesion molecule (CEACAM5) expression as per central assessment on tumor biospsy • Eastern Cooperative Oncology Group (ECOG) performance status 0-1. • Female participant who agrees to use effective contraceptive methods during and for at least 7 months after the last dose of treatment administration • Male participant who agrees to use effective contraception methods during and for at least 4 months after the last dose of treatment administration • 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 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: • Untreated brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression. • Significant concomitant illness. • History within the last 3 years of an invasive malignancy other than that treated in this study • Known uncontrolled infection • Nonresolution of any prior treatment-related toxicity • Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy • Use of contact lenses • 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; subcutaneous venous access device placement within 7 days prior to Day 1; or postoperative bleeding complications or wound complications from a surgical procedure performed in the last 2 months • History of gross hemoptysis (defined as bright red blood or =1/2 teaspoon) within 2 months before the first treatment administration • Any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months before the first administration of treatment administration • 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 treatment administration • Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first administration of treatment administration • 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 • Prior treatment targeting CEACAM5 or containing maytansinoid DM1 or DM4 or ramucirumab or taxane or targeting VEGF/VEGFR • Poor organ function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Part 1: to confirm the recommended tusamitamab ravtansine loading dose Q2W in combination with ramucirumab in advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma population •Part 2: to assess the antitumor activity of tusamitamab ravtansine loading dose Q2W in combination with ramucirumab in advanced gastric or GEJ adenocarcinoma;Secondary Objective: •To assess safety •To assess durability •To assess progression-free survival (PFS) •To assess the disease control rate (DCR) •To assess the pharmacokinetics (PK) •To assess the immunogenicity ;Primary end point(s): 1.Incidence of study drug related dose-limiting toxicities (DLTs) - Part 1: Number of participants with DLTs 2.Objective Response Rate - Part 2: Objective Response Rate (ORR), defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) as best overall response (BOR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 ;Timepoint(s) of evaluation of this end point: 1. Cycle 1 (C1) and Cycle 2 (C2) (C1 Day 1 and C2 Day 14). Each cycle has a duration of 2 weeks. 2. From baseline up to approximately 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Incidence of Adverse Events - Number of participants with adverse events 2. Duration of Response - Duration of response (DOR), defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST 1.1 or death from any cause, whichever occurs first 3. Progression-free survival - Progression-free survival, 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. Disease control rate - Disease control rate, defined as the proportion of participants with confirmed CR or PR or SD as BOR per RECIST 1.1 5. Pharmacokinetic parameters of tusamitamab ravtansine and ramucirumab - Pharmacokinetic parameters of tusamitamab ravtansine and ramucirumab 6. Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine - Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine;Timepoint(s) of evaluation of this end point: 1. to 6. - From baseline up to approximately 24 months | — |
Countries
Belgium, Japan, Korea, Republic of, Russian Federation, Spain, Turkey
Contacts
Public ContactBrigitte De Witte
Sanofi Belgium
Outcome results
None listed