Gastrointestinal Cancer Trials

Astellas Protocol 8951-CL-0103

A Phase 2 Study of IMAB362 as Monotherapy or in Combination with mFOLFOX6 in Subjects with Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma whose Tumors have High or Intermediate Claudin (CLDN) 18.2 Expression.

Summary: The purpose of this study is to determine the Objective Response Rate (ORR) of zolbetuzimab as a single agent as assessed by an independent central reader. This study will also assess the ORR and Progression Free Survival (PFS) of zolbetuximab in combination with mFOLFOX6, assess the safety and tolerability, assess the effects on CLDN18.2 expression and assess the immunogenicity and immunomodulatory effects of zolbetuximab as a single agent and in combination with mFOLFOX6. This study will also evaluate the pharmacokinetics (PK) of zolbetuximab, oxaliplatin and fluorouracil (5-FU), evaluate health-Related Quality of Life (HRQoL), evaluate the Disease Control Rate (DCR), Duration of Response (DOR), PFS and Overall Survival (OS) of zolbetuximab as a single agent.

Condition or Disease:
Pharmacokinetics of Zolbetuximab
Gastric Cancer
Gastro-esophageal Junction (GEJ) Cancer
Pharmacokinetics of Oxaliplatin
Pharmacokinetics of Fluorouracil Bolus (5-FU)

Intervention/Treatment:
Drug: zolbetuximab
Drug: oxaliplatin
Drug: leucovorin
Drug: fluorouracil

Phase 2. Detailed Description: This is a study to assess the antitumor activity of zolbetuximab, an Immunoglobulin (IgG1) chimeric monoclonal antibody directed against CLDN18.2, in subjects with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors have high or intermediate CLDN18.2 expression. For each cohort, the study consists of the following periods: pre-screening; screening; treatment; and follow-up for disease progression. In addition, there will be a survival follow-up period for Cohort 1 subjects only.

Astellas Spotlight Protocol 8951-CL-0301

This trial is a phase 3, global, multi-center, double-blind, randomized, efficacy study of zolbetuximab (IMAB362) plus mFolfox6 compared with placebo plus mFolfox6 as first-line treatment of subjects with claudin(CLDN)18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Summary: A study of zolbetuximab (IMAB362) plus mFOLFOX6 versus placebo plus mFOLFOX6 in subjects with Claudin 18.2 positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.

Why is this study being done?

SPOTLIGHT is a new clinical study for adult patients who have any of:

• advanced unresectable gastric or GEJ cancer.
• metastatic gastric or GEJ cancer These types of cancers have a unique set of proteins (called Claudin 18.2). We may be able to use a treatment that targets the proteins to kill the cancer cells.

For patients with one of the types of cancer listed above, mFOLFOX6 (a combination of three chemotherapies known as Oxaliplatin, Leucovorin, and Fluorouracil) is a current treatment option. This study is testing an experimental medicine called zolbetuximab (IMAB362). Zolbetuximab attaches itself to Claudin 18.2 on the cancer cells causing cancer cell death.

Patients will be assigned to one of two groups by chance and given either:

• zolbetuximab with mFOLFOX6; or
• a placebo with mFOLFOX6 A placebo is a treatment that looks like the experimental medicine, but contains no medicine.

The goal of the study is to find out if zolbetuximab with mFOLFOX6 helps patients to live longer by stopping the cancer from getting worse.

Condition or Disease:
Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer
Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer
Metastatic Gastric Adenocarcinoma or Cancer
Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma

Intervention/Treatment:
Drug: zolbetuximab
Drug: placebo
Drug: oxaliplatin
Drug: folinic acid
Drug: fluorouraci

Phase 3. Detailed Description: The study consists of the following periods: screening; treatment; post-treatment follow up, safety follow up, long term and survival follow-up.