A trial to learn how well AZD0901 works and how safe it is compared to standard cancer treatments in adults with advanced and metastatic gastric or gastroesophageal junction cancers with high levels of a protein called CLDN18.2

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Jan 2025 → ongoing

Decision date (initial)

2024-07-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Efficacy, Pharmacokinetic

To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of PFS in all randomized participants. To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS for 3L+ participants

Secondary objectives 9

1. To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS in all randomized participants
2. To demonstrate the effectiveness of AZD0901 relative to Investigator’s choice of therapy by assessment of PFS for 3L+ participants
3. To demonstrate the effectiveness of AZD0901 relative to Investigator’s choice of therapy by assessment of ORR in all randomized participants
4. To demonstrate the effectiveness of AZD0901 relative to Investigator’s choice of therapy by assessment of ORR for 3L+ participants
5. To demonstrate the effectiveness of AZD0901 relative to Investigator’s choice of therapy by assessment of DoR in all randomized participants
6. To demonstrate the effectiveness of AZD0901 relative to Investigator’s choice of therapy by assessment of DoR for 3L+ participants
7. To assess the PK of AZD0901
8. To assess the immunogenicity of AZD0901
9. To assess the safety and tolerability of AZD0901 as compared with Investigator’s choice of therapy in all randomized participants who have received at least one dose of study intervention

Conditions and MedDRA coding

Gastric cancer, Advanced/Metastatic Gastric cancer, Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be at least 18 years or the legal age of consent in the jurisdiction
2. Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement a) With positive CLDN 18.2 expression determined by central lab. For participants who have received prior CLDN18.2 targeting therapies a new biopsy upon progression must be provided for testing to determine CLDN18.2 expression.
3. Disease progression on or after at least one prior line of treatment (LoT), which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.
4. Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1
5. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
6. Predicted life expectancy of ≥ 12 weeks
7. Adequate organ and bone marrow function as show in table in full CSP
8. Body weight of ≥ 35 kg
9. Sex and contraceptive requirements

Exclusion criteria 8

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, or aphasia 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. The following are exceptions to this criterion: (a) Participants with history of seizures are permitted if no active seizures in last 5 years. (b) Participants with brain metastases treated, asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to randomization. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrolment.
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).
7. History of thromboembolic events
8. As judged by the Investigator, any evidence of diseases which in the Investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PFS in all randomized participants (BICR)
2. OS for 3L+ participants

Secondary endpoints 9

1. OS in all - time from randomization until the date of death due to any cause.
2. PFS for 3L+ participants- time from randomization until progression per RECIST 1.1 asassessed by BICR or death due to any cause.
3. ORR in all- the proportion of participants with at least one visit response of confirmed CR or confirmed PR, as determined by BICR per RECIST 1.1.
4. ORR for 3L+ participants
5. DoR in all- the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause.
6. DoR for 3L+ participants
7. Serum concentrations of AZD0901, total antibody and MMAE, and PK parameters
8. Presence of ADAs against AZD0901 in serum
9. Incidence of AEs and SAEs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

5 EU/EEA countries · 44 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 54 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications