AZD0901 Compared With Investigator's Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Gastroesophageal Junction Cancer; Gastric Cancer

Treatments: Drug: AZD0901; Drug: Docetaxel; Drug: Irinotecan; Drug: Ramucirumab+ paclitaxel; Drug: TAS-102; Drug: Paclitaxel; Drug: Apatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06346392

D9802C00001

2023-508276-11-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to measure the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2.

Full description

This is a Phase III, multi-center, open-label, sponsor-blinded, randomized, global study to assess the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as the 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2, and the clinical performance of the investigational IVD. As part of this combined approach, the efficacy analyses from this study will also provide the basis to evaluate the clinical performance of Ventana CLDN18.2 assay as an IVD device for the identification of patients with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2 who may benefit from AZD0901.

Enrollment: 589 estimated patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Capable of giving signed informed consent prior to any study procedure.

2. Participant must be at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.

3. Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement:

   (a) Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy.

4. Disease progression on or after at least one prior line of treatment (LoT) for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.

5. Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.

6. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.

7. Predicted life expectancy of ≥ 12 weeks.

8. Adequate organ and bone marrow function

9. Body weight of ≥ 35 kg.

10. Sex and Contraceptive Requirements

Exclusion criteria

1. Participants with known HER2 positive status as defined as IHC 3+ or IHC 2+/ISH + (Cases with HER2: CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals/cell are considered positive by ISH). Participants must undergo local (or have had) HER2 testing by IHC/ISH, and the most recent result of HER2 status will be used to determine the eligibility.
2. Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
3. CNS metastases or CNS pathology including: epilepsy, seizures, aphasia, or stroke within 3 months prior to consent, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.
4. Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
5. Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
6. Prior exposure to any ADC with MMAE payload or any CLDN18.2 targeting treatment other than naked monoclonal antibody (eg, CLDN18.2 targeting CAR-T cell therapy, multi-specific antibody including targeting CLDN18.2, etc).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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589 participants in 3 patient groups

AZD0901 arm 1

Experimental group

Description:

Participants in the AZD0901 arm 1 will receive AZD0901 dose level 1 intravenous infusion treatment.

Treatment:

Drug: AZD0901

Drug: AZD0901

AZD0901 Arm 2

Experimental group

Description:

Participants in the AZD0901 arm 2 will receive AZD0901 dose level 2 intravenous infusion treatment.

Treatment:

Drug: AZD0901

Drug: AZD0901

Investigator's choice arm

Active Comparator group

Description:

Participants in the Investigator's choice arm will receive a regimen of Investigator's choice, including regionally accepted chemotherapies or targeted therapies.

Treatment:

Drug: Apatinib

Drug: Paclitaxel

Drug: TAS-102

Drug: Ramucirumab+ paclitaxel

Drug: Irinotecan

Drug: Docetaxel