A Phase II, Open-label, Multi-centre Study to Evaluate Safety, Tolerability, Efficacy, PK, and Immunogenicity of AZD0901 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Tumours Expressing Claudin 18.2 (CLARITY-PanTumour01)

More details:

Overview

AZD0901 (sonesitatug vedotin; formerly CMG901) is an investigational antibody–drug conjugate (ADC) targeting claudin 18.2 (CLDN18.2), being developed primarily for gastric/gastroesophageal junction (G/GEJ) adenocarcinoma and other CLDN18.2-expressing solid tumors. Early-phase clinical data show antitumor activity with a manageable safety profile in previously treated CLDN18.2-positive G/GEJ cancer, and multiple phase 2 and phase 3 trials are ongoing. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

• Target: CLDN18.2, a tight-junction protein aberrantly exposed in several gastrointestinal cancers. (pubmed.ncbi.nlm.nih.gov)
• Construct: Humanized anti‑CLDN18.2 IgG1 linked via a protease‑cleavable linker to monomethyl auristatin E (MMAE; “vedotin”). The ADC mediates direct cytotoxicity after internalization and MMAE release, plus immune effector functions (ADCC/CDC) and a bystander effect. (pubmed.ncbi.nlm.nih.gov)

Efficacy

• Phase 1 (KYM901, NCT04805307) in advanced G/GEJ cancer (mostly CLDN18.2-positive; Q3W dosing 2.2–3.0 mg/kg):
• Confirmed ORR 28% (95% CI 20–38; 32/113) in the full analysis set; ORR 29% (95% CI 21–39; 32/109) in the efficacy set; recommended phase 2 dose (RP2D) 2.2 mg/kg. Median follow-up 9.0 months. (pubmed.ncbi.nlm.nih.gov)
• Earlier ASCO abstract reported, among 93 CLDN18.2-positive patients, confirmed ORR 32.6% and median PFS 4.76 months; 9‑month OS rate 56.4%. Data cutoff July 24, 2023. (ascopubs.org)

Ongoing trials (selected): - CLARITY-PanTumor01 (Phase 2, NCT06219941): AZD0901 monotherapy and combinations in advanced CLDN18.2-expressing tumors (G/GEJ, PDAC); primary endpoints include safety and ORR. Recruitment began December 2023. (ascopubs.org) - GEMINI-Gastric (Master Phase 2, NCT05702229): evaluates novel agents including AZD0901 in combination with chemotherapy/immunotherapy in metastatic gastric cancer. (ascopubs.org) - Randomized Phase 3 (NCT06346392): AZD0901 vs ramucirumab/paclitaxel (or investigator’s taxane) in second-line G/GEJ adenocarcinoma; primary completion estimated April 2026. (cdek.pharmacy.purdue.edu)

Safety

• Phase 1 dose-escalation/expansion:
• Most common treatment-emergent adverse events (any grade): vomiting, decreased appetite, proteinuria, anemia. Grade ≥3 AEs most frequently included decreased neutrophil count (≈21%), anemia (≈14%), and vomiting (≈10%); one treatment-related death reported. Maximum tolerated dose not reached; RP2D 2.2 mg/kg Q3W. (pubmed.ncbi.nlm.nih.gov)
• Earlier ASCO readout listed common AEs: anemia, vomiting, hypoalbuminemia; grade ≥3 neutrophil count decreased 18.6% and anemia 13.3%. (ascopubs.org)

Class-related considerations: As an MMAE-bearing ADC, AZD0901’s toxicity profile aligns with other vedotin ADCs (e.g., myelosuppression, GI AEs), consistent with preclinical findings attributing reversible hematopoietic changes to the payload. (pubmed.ncbi.nlm.nih.gov)

Additional notes

• Naming and sponsorship: Originally developed as CMG901 by KYM Biosciences (Keymed/Lepu); globally licensed to and now developed by AstraZeneca (AZD0901; USAN nonproprietary name sonesitatug vedotin). (news.cision.com)
• Dosing schedule under study: Intravenous administration every 3 weeks (Q3W). RP2D 2.2 mg/kg in Phase 1. (pubmed.ncbi.nlm.nih.gov)

Further reading

• Phase 1 G/GEJ cancer results (Lancet Oncology 2025; PubMed): https://pubmed.ncbi.nlm.nih.gov/39788133/ (pubmed.ncbi.nlm.nih.gov)
• ASCO 2023 abstract with efficacy by dose cohort: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.36_suppl.434420 (ascopubs.org)
• Phase 2 CLARITY-PanTumor01 design (ASCO 2024 TPS): https://ascopubs.org/doi/abs/10.1200/JCO.2024.42.16_suppl.TPS3163 (ascopubs.org)
• Preclinical characterization of CMG901: https://pubmed.ncbi.nlm.nih.gov/39232496/ (pubmed.ncbi.nlm.nih.gov)
• Phase 3 trial listing (NCT06346392): https://cdek.pharmacy.purdue.edu/trial/NCT06346392/ (cdek.pharmacy.purdue.edu)
• AstraZeneca development overview/announcement: https://news.cision.com/astrazeneca/r/astrazeneca-completes-kym-agreement-for-cmg901%2Cc3743484 (news.cision.com)

Notes on data currency: Phase 1 efficacy and safety were updated through Feb 24, 2024 in the Lancet Oncology report (published 2025). Phase 2 and Phase 3 trials are ongoing as of the latest updates in 2024–2025; no randomized efficacy results have been reported yet. (pubmed.ncbi.nlm.nih.gov)

Last updated: Oct 2025

The list below is a summarised eligibility criteria for the study - refer to the study protocol for full criteria.

Master Inclusion Criteria applicable to all sub studies:

* Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF.

* Participants who are CLDN18.2 positive.

* Must have at least one measurable lesion according to RECIST v1.1.

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

* Predicted life expectancy of ≥ 12 weeks.

* Adequate organ and bone marrow function as defined by protocol.

* Body weight \> 35 kg.

* Participants are willing to comply with contraception requirements.

Sub study 1 Specific Inclusion criteria:

* Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction.

* Advanced or metastatic GC/GEJC.

* Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.

Sub study 2 Specific Inclusion criteria:

* Participants diagnosed with histologically confirmed metastatic or advanced PDAC.

* Availability of an archival sample or a fresh tumour biopsy taken at screening.

* No prior treatments for unresectable or metastatic disease. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months (183 days) from the last dose.

Sub study 3 Specific Inclusion criteria

* Histologically confirmed, unresectable advanced, or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (NOTE: Ampullary cancers are not eligible).

* Documented radiographic or clinical disease progression on or after at least one prior regimen and maximum 2 prior lines of systemic treatment for unresectable or metastatic disease.

Master Exclusion Criteria applicable to all sub studies:

* Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy.

* Participants with clinically significant ascites that require drainage.

* A history of drug-induced non-infectious ILD/pneumonitis.

* Central nervous system metastases or CNS pathology.

* Peripheral neuropathy, sensory, or motor ≥ Grade 2 at screening.

* History of another primary malignancy.

* Prior exposure to any MMAE-based ADC.

* Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody.

Sub study 1 Specific Exclusion criteria:

* Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC unless they have failed/not tolerated/or are not eligible for standard anti-HER2 therapy, where available.

* Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.

* The use of concomitant medications known to prolong the QT/QTc interval.

Sub study 2 Specific Exclusion criteria:

* Known DPD enzyme deficiency based on local testing where testing is SoC.

* Use of strong inhibitor or inducer of UGT1A1.

* Use of strong inhibitors or inducers of CYP3A4.

* Known homozygous for the UGT1A1\*28 allele based on local testing where testing is SoC.

Sub study 3 Specific Exclusion criteria

• Clinically significant biliary obstruction that has not resolved before enrollment.