sonesitatug vedotin (AZD0901) / Keymed Biosciences, Lepu Med, AstraZeneca - LARVOL DELTA

AZD0901 monotherapy in patients (pts) with advanced biliary tract cancer (BTC) expressing Claudin18.2 (CLDN18.2): CLARITY-PanTumour01 Substudy 3 (ESMO-GI 2025) - No abstract available

Clinical • Metastases • Monotherapy • Pan tumor • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • CLDN18

VBC108: a first-in-class CDH17/CLDN18.2 targeted bispecific antibody drug conjugate (ADC) to overcome tumor heterogeneity of gastrointestinal cancers (GC, PADC, CRC, etc.) (AACR 2025) - "However, these therapies face challenges due to the heterogeneous expression of CLDN18.2, leading to inconsistent efficacy and the need of patient stratification, as observed with Zolbetuximab, AZD0901 and IBI343. VBC108 also exhibited excellent developability in a comprehensive developability assessment (DA) test, making it a strong candidate for further CMC development. In summary, VBC108, with its unique design, shows the potential as a first-in-class ADC for GI cancer and supports the advancement to clinical trials."

Heterogeneity • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CDH17 • CLDN18

CLARITY-Gastric 01: a randomized Phase 3 study of AZD0901 in 2L+ advanced gastric/gastroesophageal junction cancers (JSMO 2025) - No abstract available

Clinical • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

KYM901: Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy, Phase 1 Study of CMG901 (clinicaltrials.gov) - P1 | N=176 | Completed | Sponsor: Keymed Biosciences Co.Ltd | Recruiting ➔ Completed | Trial completion date: Oct 2024 ➔ Apr 2024

Trial completion • Trial completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

GEMINI-Gastric: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2026 ➔ Jan 2027 | Trial primary completion date: Sep 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18

CLARITY-Gastric 01: A randomized phase 3 study of AZD0901, a Claudin18.2 (CLDN18.2)-targeted antibody-drug conjugate, in second- or later-line (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC). (ASCO-GI 2025) - P3 | " Participants (pts) will be randomized 1:1:1 to AZD0901 dose level 1 intravenous (IV) every three weeks (Q3W; Arm 1), AZD0901 dose level 2 IV Q3W (Arm 2), or INV choice of therapy (2L: ramucirumab [ram] + paclitaxel [PTX], PTX, or docetaxel [for pts with contraindication to ram only]; 3L+: irinotecan, TAS-102 [excluding China], or apatinib [China only]; Arm 3). Previously presented at European Society for Medical Oncology - Gastrointestinal Cancers Congress 2024, Final Publication Number: 495TiP, Kohei Shitara et al. Reused with permission."

Clinical • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • HER-2

CLARITY-PanTumor01: AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2 (clinicaltrials.gov) - P2 | N=190 | Recruiting | Sponsor: AstraZeneca | N=123 ➔ 190 | Trial primary completion date: May 2025 ➔ Dec 2025

Enrollment change • Monotherapy • Trial primary completion date • Biliary Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

Claudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial. (PubMed, Lancet Oncol) - P1 | "CMG901 showed a manageable safety profile and had promising antitumour activity in patients with advanced gastric or gastro-oesophageal junction cancer."

Journal • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Disorders • Hepatology • Oncology • Pancreatic Cancer • Pancreatitis • Renal Disease • Solid Tumor • CLDN18

Claudin 18.2-targeting antibody–drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial (Lancet Oncol) - P1 | N=162 | NCT04805307 | Sponsor: Keymed Biosciences Co.Ltd | "At median follow-up of 9·0 months (IQR 4·4–12·9), among 113 patients with gastric or gastro-oesophageal junction cancer in the 2·2–3·0 mg/kg cohort full analysis set across both the dose-escalation and dose-expansion phases, the confirmed objective response rate was 28% (95% CI 20–38; 32 of 113 patients). In the 109 patients included in the efficacy analysis set, the confirmed objective response rate was 29% (95% CI 21–39; 32 of 109 patients). Based on overall safety, activity, and pharmacokinetics of CMG901, 2·2 mg/kg was the proposed recommended phase 2 dose."

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

CLARITY-Gastric 01: a randomized Phase 3 study of AZD0901, a Claudin18.2 (CLDN18.2)-targeted antibody drug conjugate, in second- or (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC) (KINGCA Week 2024) - No abstract available

Clinical • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

Claudin 1, 4, 6 and 18 isoform 2 as targets for the treatment of cancer (Review). (PubMed, Int J Mol Med) - "The human/humanized anti‑CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM‑302, with single‑agent ORRs of 28‑60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti‑CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration."

Journal • Review • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • CLDN1 • CLDN18 • CLDN4 • CLDN6

CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors. (PubMed, Cell Rep Med) - P3 | "CMG901's favorable preclinical profile supports its entry into the human clinical study. CMG901 is currently under phase 3 investigation in patients with advanced gastric/gastroesophageal junction adenocarcinoma expressing Claudin18.2 (NCT06346392)."

Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

Keymed Biosciences Announces Interim Results for First Half of 2024 (PRNewswire) - "As of the date of this announcement...an international multi-center Phase III study comparing CMG901...monotherapy versus investigator's choice as second-line or later-line treatment in patients with advanced or metastatic gastric and gastroesophageal junction (G/GEJ) cancer expressing Claudin 18.2 was publicly announced on the drug clinical trial registration and information publicity platform in March 2024. The first patient has received the initial dose in April 2024....Continuously proceeded with a Phase I/II clinical trial in the first half of 2024 to assess the safety, tolerability, pharmacokinetics, and the preliminary anti-tumor activity of CM355 in relapsed or refractory non-Hodgkin's lymphoma (NHL). As of the date of this announcement, dose escalation of the intravenous infusion formulation (IV) was completed and the subcutaneous formulation (SC) is in the process of patient evaluation."

Trial status • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

CLARITY-Gastric 01: A randomised phase III study of AZD0901, a Claudin18.2 (CLDN18.2)-targeted antibody-drug conjugate, in second- or later-line (2L+) advanced gastric or gastroesophageal junction cancer (GC/GEJC) (ESMO-GI 2024) - P3 | "CLARITY-Gastric 01 (NCT06346392) is a randomised, open-label, sponsor-blinded, global phase 3 study that will assess the efficacy and safety of AZD0901 vs investigator's (INV) choice of therapy after ≥1 prior therapy for advanced GC/GEJC expressing CLDN18.2.Trial design: Participants (pts) will be randomised to AZD0901 dose level 1 intravenous (IV) every three weeks (Q3W), AZD0901 dose level 2 IV Q3W or INV choice of therapy (2L: ramucirumab [ram] + paclitaxel [PTX], PTX or docetaxel [for pts with contraindication to ram only]; 3L+: irinotecan, TAS-102 [excluding China] or apatinib [China only]). Dual primary endpoints are progression-free survival (PFS; intent-to-treat [ITT] pts) and OS (3L+ pts). The secondary endpoints include OS (ITT pts), PFS (3L+ pts), objective response rate and duration of response (ITT and 3L+ pts), and safety/tolerability."

Clinical • Metastases • P3 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • HER-2

AZD0901: “AZD0901 - Promising clinical efficacy in pretreated patients with CLDN18.2-high gastric/GEJ cancer”; Gastric cancer (AstraZeneca) - ASCO 2024: “AZD0901 was generally well-tolerated, with a manageable safety profile”

P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology

CLARITY-PanTumor01: A phase 2 trial of the claudin 18.2-specific antibody-drug conjugate AZD0901 (CMG901) in patients with CLDN18.2-expressing advanced solid tumors. (ASCO 2024) - P1, P2 | "Substudy 2 is recruiting patients with previously untreated CLDN18.2-expressing metastatic PDAC to receive AZD0901 (up to 2.2 mg/kg IV Q3W) and either a combination of 5-fluorouracil 2400 mg/m 2 IV on Days 1 and 2 Q2W, leucovorin 400 mg/m 2 or l-leucovorin 200 mg/m 2 IV on Days 1 and 2 Q2W, and irinotecan 150 or 180 mg/m 2 or nanoliposomal irinotecan 50 mg/m 2 IV on Day 1 Q2W (Arm 1), or gemcitabine 1000 mg/m 2 IV on Days 1 and 8 Q3W (Arm 2), per investigator's choice. Secondary endpoints include overall survival, progression-free survival, duration of response, disease control rate, best change in target lesion size, pharmacokinetics, immunogenicity, and pharmacodynamics. Recruitment began in December 2023, and sites across Australia, Asia, Europe, and North America will enroll patients."

Clinical • Metastases • P2 data • Pan tumor • Gastric Cancer • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Peptic Ulcer • Solid Tumor • CLDN18 • HER-2

Updates on Abstract 434420: A Phase 1 Trial of Claudin 18.2-Specific Antibody-Drug Conjugate CMG901 in Patients with Advanced Gastric/Gastroesophageal Junction Cancer (ASCO 2024) - No abstract available

Clinical • Metastases • P1 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

GEMINI-Gastric: A phase 2 study of novel treatment combinations in patients with locally advanced unresectable or metastatic gastric cancers. (ASCO 2024) - P2 | "Novel agents include: volrustomig, an anti-PD-1/CTLA-4 bispecific humanized IgG1 monoclonal antibody (mAb); rilvegostomig, an anti-PD-1/TIGIT bispecific humanized IgG1 mAb; AZD0901, a claudin18.2-targeted antibody-drug conjugate; and AZD7789, an anti-PD-1/TIM-3 bispecific mAb. Sample sizes have been selected to provide adequate precision for the primary endpoints. The study is currently recruiting at sites in the US, Europe, and Asia."

Clinical • IO biomarker • Metastases • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • HAVCR2 • HER-2 • TIGIT

AZD0901: Data from P2 trial (NCT06219941) for locally advanced or unresectable or metastatic solid tumors post 2025 (AstraZeneca) - Q1 2024 Results: Data from P3 CLARITY - Gastric01 trial (NCT06346392) for 2L+ advanced or metastatic gastric or GEJ adenocarcinoma post 2025

P2 data • P3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

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 (clinicaltrials.gov) - P3 | N=589 | Recruiting | Sponsor: AstraZeneca

New P3 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

New CLDN18.2 protein offers breakthrough in stomach cancer treatment (Korea Biomedical Review) - "As the Claudin 18.2 protein, also called CLDN18.2, emerges as a new target for treating gastric cancer, Astellas' first CLDN18.2-targeted cancer drug, zolbetuximab, is in the final stage of its launch, drawing the industry’s attention. However, the changing landscape of metastatic gastric cancer treatment and the rapid development of follow-on therapies make it unclear whether zolbetuximab will claim the 'first in class' title in the market, according to industry insiders....Based on these findings, zolbetuximab is under review for approval in the U.S., China, and Japan. It is also preparing to get approval in Korea next year....Expectations that ADCs containing cytotoxic anticancer agents, such as CMG901 and ATG-022, will show better therapeutic outcomes than traditional monoclonal antibodies have market insiders paying attention to how their clinical trial results and market access will impact the competitive landscape in gastric cancer treatment."

Launch • Non-US regulatory • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

AZD0901: Data from P2 trial (NCT06219941) for locally advanced or unresectable or metastatic solid tumors in Q1 2027 (AstraZeneca) - Q4 & FY2023 Results

P2 data • Oncology • Solid Tumor

AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2 (clinicaltrials.gov) - P2 | N=123 | Recruiting | Sponsor: AstraZeneca

Combination therapy • Metastases • Monotherapy • New P2 trial • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • CLDN18

Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: AstraZeneca | N=80 ➔ 240

Enrollment change • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

Optimism Surrounds Claudin 18.2 ADC. (PubMed, Cancer Discov) - "Historically, progression-free survival (PFS) hovers around 7 months and overall survival (OS) around 14 to 16 months. However, depending on the dose, PFS with CMG901 ranged from 3.3 to 14.5 months, and OS ranged from 8.5 months to not reached, after a median follow up of 6 months."

Journal • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18