Trial: AZD0901 Compared With Investigator's Ch…

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 3

Start date: March 4, 2024

Planned enrollment: 572

Trial ID: NCT06346392

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: AZD0901 (Sonesitatug vedotin, CMG901)

Overview

AZD0901, also called sonesitatug vedotin or CMG901, is an investigational antibody–drug conjugate being studied primarily in claudin 18.2 (CLDN18.2)–expressing gastric and gastroesophageal junction cancers. Human results are available from phase 1 and phase 2 studies. A phase 3 trial has also reported preliminary results, but detailed comparative data have not yet been published. (sciencedirect.com)

Mechanism of action

The drug links an antibody targeting CLDN18.2 to monomethyl auristatin E (MMAE), a substance that disrupts the cellular structures needed for cell division. A cleavable linker is designed to release MMAE after the antibody–drug conjugate enters a target cell. (sciencedirect.com)

Efficacy

In the single-arm phase 1 KYM901 trial, 32 of 113 patients (28%) with advanced gastric or gastroesophageal junction cancer had a confirmed tumor response at doses of 2.2–3.0 mg/kg. In the phase 2 CLARITY-PanTumor01 study, the reported response rate was 28.4% among 67 patients receiving 2.2 mg/kg; median progression-free survival was 4.2 months. Neither study alone establishes how the drug compares with standard treatment. (em-consulte.com)

In July 2026, the sponsor announced that the randomized phase 3 CLARITY-Gastric01 trial found an overall-survival improvement versus investigators’ choice of treatment in previously treated CLDN18.2-expressing cancer. The announcement did not provide survival estimates or effect sizes. Its other primary endpoint, progression-free survival in the second-line-or-later population, did not reach statistical significance. These findings remain difficult to assess fully until detailed results are released. (astrazeneca.com)

Safety

In KYM901’s 107-patient dose-expansion group, 68% experienced a grade 3 or worse adverse event. The most common grade 3–4 events were decreased neutrophil count (21%), anemia (14%), and vomiting (10%); one treatment-related death was reported. In the phase 2 report, 34.3% of 67 patients had grade 3 or worse adverse events, and 40.3% required a dose reduction. The phase 3 announcement did not provide detailed safety rates. (em-consulte.com)

Show for: Apatinib (Rivoceranib)

Overview

Apatinib, also called rivoceranib, is an oral cancer drug studied alone and in combination with other treatments. It has been approved in China for some patients with advanced gastric cancer; its use in other settings remains under investigation. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

Apatinib inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2). By blocking this signaling pathway, it aims to reduce the formation of blood vessels that support tumor growth. (pmc.ncbi.nlm.nih.gov)

Efficacy

Results vary by cancer type and treatment regimen:

Previously treated gastric or gastroesophageal junction cancer: In a Chinese phase 3 trial, median overall survival was 6.5 months with apatinib versus 4.7 months with placebo. A separate international phase 3 trial, ANGEL, did not meet its primary overall-survival endpoint, although progression-free survival and response rate improved: responses occurred in 6.5% versus 1.3% of patients. (pubmed.ncbi.nlm.nih.gov)
Radioactive iodine–refractory differentiated thyroid cancer: In the 92-patient REALITY phase 3 trial, median progression-free survival was 22.2 versus 4.5 months, and confirmed response rates were 54.3% versus 2.2%, for apatinib and placebo respectively. (jamanetwork.com)
Unresectable liver cancer: In the phase 3 CARES-310 trial, camrelizumab plus rivoceranib yielded median overall survival of 23.8 months versus 15.2 months with sorafenib. The combination’s confirmed response rate was 25% versus 6%. These results assess the combination, not rivoceranib alone. (pubmed.ncbi.nlm.nih.gov)

Safety

Prominent adverse effects include high blood pressure, hand-foot syndrome, proteinuria, and diarrhea. In REALITY, 73.9% of apatinib-treated patients had a grade 3 or higher treatment-related adverse event. In CARES-310, grade 3 or 4 treatment-related hypertension occurred in 38% receiving the combination versus 15% receiving sorafenib; serious treatment-related adverse events occurred in 25% versus 7%. The ANGEL trial reported treatment-related adverse events resulting in death in 2.6% of rivoceranib-treated patients versus 1.3% of placebo-treated patients. (pmc.ncbi.nlm.nih.gov)

TrialFetch AI Analysis

Goal: Compare the efficacy and safety of AZD0901 with investigator-selected therapy in second- or later-line CLDN18.2-expressing advanced gastric or gastroesophageal junction adenocarcinoma, while evaluating a CLDN18.2 assay for patient selection.

Patients: Adults with unresectable locally advanced or metastatic gastric, gastroesophageal junction, or distal esophageal adenocarcinoma; CLDN18.2-positive tumor tissue; and progression after at least one advanced-disease regimen containing a fluoropyrimidine and platinum. Participants need ECOG performance status 0–1 and measurable or evaluable disease. HER2-positive disease is excluded.

Design: Global, multicenter, randomized, open-label, sponsor-blinded comparison of AZD0901 with investigator’s choice of therapy. A second AZD0901 dose-level arm was included, but enrollment to that arm has closed.

Treatments: AZD0901 (sonesitatug vedotin; CMG901) is given by intravenous infusion. It is an investigational antibody–drug conjugate that targets CLDN18.2 and delivers the microtubule-disrupting payload MMAE into target cells. Earlier single-arm studies reported response rates of approximately 28%; a preliminary phase 3 sponsor announcement reported an overall-survival improvement versus investigator’s choice but no statistically significant progression-free-survival benefit in the second-line-or-later population, without detailed comparative estimates. Investigator’s choice includes ramucirumab plus paclitaxel, paclitaxel, docetaxel, irinotecan, TAS-102, or apatinib, according to regional practice.

Outcomes: Primary endpoints are progression-free survival in all randomized participants and overall survival among those treated in the third line or later. Secondary measures include overall survival and progression-free survival in the other specified populations, objective response, duration of response, adverse events, laboratory and ECG changes, AZD0901 pharmacokinetics, and antidrug antibodies.

Burden on patient: Moderate. Participants need archival tumor tissue or a fresh biopsy for CLDN18.2 testing, regular treatment and imaging visits, and safety assessments. AZD0901 recipients also have infusion visits and additional blood draws for pharmacokinetic and immunogenicity testing. The schedule of scans and blood draws is not specified, so the precise travel and testing burden cannot be determined.

Last updated: Sep 2026

Eligibility

Show 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.

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 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.

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:

1. Participants with venous thromboembolism within the past 6 months prior to randomization: participants with venous port or catheter thrombosis or superficial venous thrombus that do not require treatment or are stable on treatment with anticoagulants are excepted

2. History of arterial thromboembolism within the past 12 months prior to randomization

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.

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