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

Study identifier:D9802C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A Phase III Multi-center, Open-label, Sponsor-blinded, Randomized Study of AZD0901 Monotherapy Compared with Investigator’s Choice of Therapy in Second- or Later-Line Adult Participants with Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2

Medical condition

gastric cancer, Gastroesophageal Junction Cancer

Phase

Phase 3

Healthy volunteers

Study drug

AZD0901, Ramucirumab+ paclitaxel, Paclitaxel, Docetaxel, Irinotecan, TAS-102, Apatinib

Sex

All

Estimated Enrollment

589

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 04 Mar 2024

Estimated Primary Completion Date: 10 Apr 2026

Estimated Study Completion Date: 09 Oct 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

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.
(b) Participants must undergo local (or have had) HER2 testing by IHC/ISH.
4. Disease progression on or after at least one prior regimen 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).

Sort by status

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Arms	Assigned Interventions
Experimental: AZD0901 arm 1 Participants in the AZD0901 arm 1 will receive AZD0901 dose level 1 intravenous infusion treatment.	Drug: AZD0901 Participants in the AZD0901 arm 1 will receive dose level 1 AZD0901 IV
Experimental: AZD0901 Arm 2 Participants in the AZD0901 arm 2 will receive AZD0901 dose level 2 intravenous infusion treatment.	Drug: AZD0901 Participants in the AZD0901 arm 2 will receive dose level 2 AZD0901 IV
Active Comparator: Investigator's choice arm Participants in the Investigator’s choice arm will receive a regimen of Investigator’s choice, including regionally accepted chemotherapies or targeted therapies.	Drug: Ramucirumab+ paclitaxel Ramucirumab 8 mg/kg IV on Days 1 and 15 and paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W Drug: Paclitaxel Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only) Drug: Docetaxel Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only) Drug: Irinotecan Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W Drug: TAS-102 TAS-102 35 mg/m2 up to a maximum of 80 mg orally twice a day on Days 1 to 5 and Days 8 to 12, Q4W (except China) Drug: Apatinib Apatinib 500-850 mg at Investigator’s discretion based on participant’s condition and tolerability, orally once daily, Q4W (China only)

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]