AZD0901

Shows activity

Also known as:

Sonesitatug vedotin CMG901

Cancer types include:

pancreas cancer stomach cancer

HealthScout AI Analysis

Show HealthScout AI Analysis

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)

Active trials using AZD0901

Found 3 active trials using this drug:

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 (CLARITY Gastric 01)

Sponsor: AstraZeneca (industry) Phase: 3 Start date: March 4, 2024

HealthScout AI summary: Adults with unresectable, advanced/metastatic gastric or GEJ adenocarcinoma that is CLDN18.2-positive after at least one prior fluoropyrimidine/platinum regimen (ECOG 0–1; HER2-negative) are randomized to AZD0901 (sonesitatug vedotin), a CLDN18.2-targeted MMAE antibody–drug conjugate, versus investigator’s choice of standard therapies (e.g., ramucirumab/paclitaxel, paclitaxel, docetaxel, irinotecan, TAS-102, or apatinib). Trial excludes prior MMAE ADCs or non-antibody CLDN18.2 therapies and recent significant bleeding/CNS disease.

ClinicalTrials.gov ID: NCT06346392

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)

Sponsor: AstraZeneca (industry) Phase: 2 Start date: Dec. 13, 2023

HealthScout AI summary: Adults with CLDN18.2-positive advanced solid tumors—specifically gastric/GEJ adenocarcinoma (post up to two lines), untreated metastatic pancreatic ductal adenocarcinoma, and previously treated biliary tract cancer—are enrolled to receive the CLDN18.2-targeted antibody–drug conjugate AZD0901 (sonesitatug vedotin, MMAE payload) as monotherapy or combined with standard pancreatic chemotherapy backbones. Suitable for ECOG 0–1 patients without prior MMAE-ADC or CLDN18.2 therapy (except mAbs) and without significant GI bleeding, ILD/pneumonitis, CNS mets, or grade ≥2 neuropathy.

ClinicalTrials.gov ID: NCT06219941

An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Immunogenicity of Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Sponsor: AstraZeneca (industry) Phase: 2 Start date: Jan. 16, 2023

HealthScout AI summary: First-line, unresectable/metastatic gastric or GEJ adenocarcinoma (ECOG 0–1), predominantly HER2-negative; some substudies require Claudin18.2-positive tumors. Non-randomized cohorts test bispecific checkpoint antibodies—PD-1/CTLA-4 (volrustomig), PD-1/TIGIT (rilvegostomig), or PD-1/TIM-3 (sabestomig)—alone with FOLFOX/XELOX or combined with a Claudin18.2-targeted MMAE ADC (AZD0901, sonesitatug vedotin) plus fluoropyrimidine.

ClinicalTrials.gov ID: NCT05702229