Clinical trial NCT05071053: Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Pretreated Participants With Gastric Cancer
Official title: Open-label Study of Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Participants Previously Treated for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma With CEACAM5-positive Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Adenocarcinoma Gastric
Gastrooesophageal Cancer
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-10-07
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

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 Objectives:

* To assess safety and tolerability
* To assess durability of response (DOR)
* To assess progression-free survival (PFS)
* To assess the disease control rate (DCR)
* To assess the pharmacokinetics (PK)
* To assess the immunogenicity

Detailed description: 34 weeks (up to 4 weeks for screening, a median of 18 weeks for treatment, and a median of 12 weeks for end-of-treatment assessments and the safety follow-up visit).

Eligibility 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

Exclusion Criteria:

* 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

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

Primary outcomes:
measure: Part 1: Number of Participants With Study-Drug Related Dose Limiting Toxicities (DLTs)
timeFrame: From Cycle 1 Day 1 to Cycle 2 Day 14; approximately 28 days
measure: Objective Response Rate (ORR)
timeFrame: Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: From the first study drug administration (Day 1) up to 30 days after the last study drug administration, approximately 92.4 weeks
measure: Duration of Response (DOR)
timeFrame: Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
measure: Progression-free Survival (PFS)
timeFrame: Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
measure: Disease Control Rate (DCR)
timeFrame: Tumor assessments performed at Baseline (Day 1), then every 6 weeks (±7 days) thereafter, approximately 88.1 weeks
measure: Individual Observed Predose Concentrations (Ctrough) of Tusamitamab Ravtansine
timeFrame: Pre-infusion on Cycle 2 Day 1
measure: Individual Observed Predose Concentrations (Ctrough) of Ramucirumab
timeFrame: Pre-infusion on Cycle 2 Day 1
measure: Number of Participants With Antitherapeutic Antibodies (ATAs) Against Tusamitamab Ravtansine
timeFrame: Upto 92.1 weeks
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Investigational Site Number : 0560002
city: Edegem
country: Belgium
facility: Investigational Site Number : 0560003
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Kashiwa-shi
country: Japan
facility: Investigational Site Number : 3920002
state: Chiba
city: Matsuyama-shi
country: Japan
facility: Investigational Site Number : 3920004
state: Ehime
city: Sapporo-shi
country: Japan
facility: Investigational Site Number : 3920001
state: Hokkaido
city: Sunto-gun
country: Japan
facility: Investigational Site Number : 3920003
state: Shizuoka
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Pushkin, Saint- Petersburg
country: Russian Federation
facility: Investigational Site Number : 6430003
state: Saint- Petersburg
city: Arkhangelsk
country: Russian Federation
facility: Investigational Site Number : 6430001
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240002
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: Granada
country: Spain
facility: Investigational Site Number : 7240004
city: Madrid
country: Spain
facility: Investigational Site Number : 7240001
city: Ankara
country: Turkey
facility: Investigational Site Number : 7920003
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Malatya
country: Turkey
facility: Investigational Site Number : 7920004
Study officials:
References: