Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Ramucirumab

Maytansine

Angiogenesis Inhibitors

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

Part 1: participants to receive an intravenous (IV) dose of tusamitamab ravtansine in combination with an IV dose of ramucirumab on Day 1 of Cycle 1 followed by an additional IV dose of tusamitamab in combination with IV dose of ramucirumab at Day 1 Cycle 2 of 14-day cycle in all subsequent cycles.

Part 2: participants to receive the recommended dose of tusamitamab ravtansine established in the Part 1 in combination with IV dose of ramucirumab on Day 1 of Cycle 1 followed by IV dose of tusamitamab in combination with IV dose of ramucirumab at Day 1 Cycle 2 of 14-day cycle in all subsequent cycles.

Pharmaceutical Form: Concentrate for solution for infusion

Route of Administration: Intravenous Infusion

Ramucirumab (CYRAMZA®)

Tusamitamab ravtansine (SAR408701)

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
* 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

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).

Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Pretreated Participants With Gastric Cancer

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

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://vivli.org

Part 1:

Number of participants with DLTs

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

Number of participants with adverse events

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

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

Disease control rate, defined as the proportion of participants with confirmed CR or PR or SD as BOR per RECIST 1.1

Incidence of antitherapeutic antibodies (ATAs) against tusamitamab ravtansine

Sanofi

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Esophageal Cancer

Trastuzumab

Fluorouracil

Immunomodulating Agents

Nivolumab

Oxaliplatin

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Week 1-12 Trastuzumab 6mg/kg d1 every 3 weeks (loading dose 8mg/kg) Nivolumab 1mg/kg i.v. d1 every 3 weeks Ipilimumab 3mg/kg i.v. d1 every 3 weeks Week 13 till EOT (max treatment period 12 months) Trastuzumab 4mg/kg d1 every 2 weeks Nivolumab 240mg i.v. d1 every 2 weeks

Trastuzumab 4mg/kg d1 every 2 weeks (loading dose 6mg/kg) Nivolumab 240mg i.v. d1 every 2 weeks mFOLFOX6 every 2 weeks Oxaliplatin at a dose of 85 mg/m2 IV over two hours (day 1) 5-FU 400 mg/m2 IV bolus (day 1) LV at a dose of 400 mg/m2 iv over two hours (day 1) 5-FU at a dose of 2400 mg/m2 IV over 46 hours (day 1-3)

Max Treatment period 12 months

Addition of Nivolumab to Standard therapy (chemotherapy and Trastuzumab)

Chemo-free immunotherapy with Nivolumab, Ipilimumab, Trastuzumab

Alexander Stein, Dr.

The INTEGA study assesses therapy Options for advanced or metastatic esophagogastric Adenocarcinoma in patients overexpressing human epidermal receptor type 2 (HER2 positive patients). Current treatment options in this situation include chemotherapy based palliative treatment in combination withTrastuzumab.

Recent studies have shown that immunotherapy with Nivolumab or Ipilimumab after previous chemotherapy can also improve survival in esophagogastric cancer.

This study assesses the efficacy of two experimental first line treatment strategies: A) Chemo-free immunotherapy with Trastuzumab, Nivolumab and Ipilimumab and B) addition of Nivolumab to the standard regimen (FOLFOX chemotherapy and Trastuzumab).

Gastric cancer is the fifth most common cancer in the world, and the third leading cause of cancer death in both sexes worldwide.

Surgical resection is currently the only curative treatment option for gastric cancer; however, \~50% of patients have metastatic disease at the time of diagnosis and chemotherapy is the mainstay of palliation in this setting.

Trastuzumab, in combination with chemotherapy, significantly improved survival in patients with overexpression of HER2.

In regard of the very limited therapeutic landscape of HER2 positive EGA, compared to breast cancer, further treatment options to relevantly improve the outcome is warranted. The integration of check-point inhibitors (e.g. Nivolumab, Ipilimumab) into the first line setting either within a chemotherapy-free combination arm or within an intensified standard arm of FOLFOX and trastuzumab with nivolumab may be able to improve the current limited survival of median 14 months.

Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in HER2 Positive EsophagoGastric Adenocarcinoma

Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in Previously Untreated HER2 Positive Locally Advanced or Metastatic EsophagoGastric Adenocarcinoma

Overall survival including milestone rate at 12 months

according to Common Terminology Criteria for Adverse Events and to the obtained data on vital signs, clinical parameters and feasibility of the regimen

Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

Response Rate (RR) according to RECIST v1.1

EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life Core Questionnaire (30 items) Version 3.0. The QLQ-C30 is composed of multi-item scales and single-item measures, including five functional scales, three symptom scales, a global health status / QoL scale, and six single items.

All of the scales and single-item measures have a score range from 0 to 100. A high score shows a high response level. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems

EORTC STO-22 (European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire Gastric Module (STO = stomach) (22 items), comprising five multi-item and four single-item subscales. The multi-item subscales include questions about dysphagia (4 items), dietary restriction (5 items), pain (3 items), upper gastro-esophageal symptoms such as reflux (3 items), and emotional problems such as anxiety (3 items). The single-item subscales include questions related to four gastric cancer-specific symptoms: dry mouth, body image, hair loss, and problems with taste. Items are assessed on a 4-level numerical scale with 1= "not at all", 2= "a little", 3= "quite a bit", and 4= "very much". Scores are linearly converted and summated into a scaled score from 0 to 100, with a higher score representing a worse QOL.

Tumor-infiltrating lymphocytes (TiL) repertoire determination from tumor

Liquid biopsy next-generation sequencing (NGS) immunoprofiling (TCRβ \& IgH) before treatment initiation and before second cycle to determine response predictive immune signature

CTC will be evaluated for changes in HER2 and PD-L1 status

ctDNA will be evaluated for HER signaling alterations

Retrospective central radiological review of ORR according to modified RECIST

Retrospective central radiological review of PFS according to modified RECIST

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Tusamitamab Ravtansine (SAR408701) in Combination With Ramucirumab in Pretreated Participants With Gastric Cancer	NCT05071053	Adenocarcinoma ... Gastrooesophage...	Ramucirumab (CY... Tusamitamab rav...	18 Years -	Sanofi
Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in HER2 Positive EsophagoGastric Adenocarcinoma	NCT03409848	Gastric Cancer Esophageal Canc... Adenocarcinoma ... HER2 Positive G... Metastatic Gast... GastroEsophagea...	Nivolumab Nivolumab Ipilimumab	18 Years -	AIO-Studien-gGmbH

Spots Global Cancer Trial Database for adenocarcinoma gastric