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

CLARITY-Gastric 01 (CG-01): a Phase 3 study of sonesitatug vedotin (Sone-Ve) in second or later-line (2L+) advanced or metastatic Claudin 18.2 (CLDN18.2) positive gastroesophageal carcinoma (GEC) (ESMO 2026) - No abstract available

Late-breaking abstract • Metastases • P3 data • Gastroesophageal Cancer • Oncology • Solid Tumor • CLDN18

CLDN18.2-Directed Therapies: From Resistance Mechanisms to Clinical Solutions (AVAHO 2026) - "Zolbetuximab, a monoclonal antibody against CLDN18.2 combined with chemotherapy, has demonstrated improved outcomes in CLDN18.2-positive, HER2-negative advanced gastric and GEJ adenocarcinomas, as shown in the phase III SPOTLIGHT and GLOW trials¹²...ADCs such as CMG901 achieved an ORR of 45%, retaining activity even in tumors with heterogeneous CLDN18.2 expression³... CLDN18.2 represents a clinically relevant therapeutic target in gastric and GEJ adenocarcinoma. Overcoming resistance through careful patient selection, combination strategies, and next-generation modalities may enhance efficacy and durability of response. Continued translational research and clinical trials are essential to define optimal treatment approaches and maximize patient benefit."

Clinical • IO biomarker • Gastroesophageal Junction Adenocarcinoma • Solid Tumor • CLDN18 • HER-2

Antibody-Drug Conjugates in the Treatment of Esophageal Cancer. (PubMed, Curr Treat Options Oncol) - "For HER2-negative gastroesophageal adenocarcinoma, trophoblast cell-surface antigen 2 represents a promising target given its high prevalence of moderate to strong expression in nearly 80% of cases, and sacituzumab tirumotecan is currently under phase III investigation in this setting...For Nectin-4-expressing tumors, enfortumab vedotin may be considered as a later-line alternative despite modest activity. Notably, the bispecific ADC targeting both epidermal growth factor receptor and human epidermal growth factor receptor 3, BL-B01D1, has demonstrated compelling efficacy in immunotherapy-refractory esophageal squamous cell carcinoma, and I consider it a breakthrough option in this subtype. For claudin-18.2-positive gastroesophageal junction adenocarcinoma, several ADCs including CMG901, IBI343, and tecotabart vedotin represent promising later-line choices. I emphasize that patient selection should be guided by validated predictive biomarkers, and treatment decisions..."

Biomarker • IO biomarker • Journal • Review • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • CLDN18 • ERBB3 • HER-2 • NECTIN4

GEMINI-Gastric: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Feb 2026 | Trial primary completion date: Jun 2024 ➔ Aug 2025

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

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

New P2 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • 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 | N=80 ➔ 240

Enrollment change • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • 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 Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • 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: Jan 2027 ➔ Jul 2027 | Trial primary completion date: Jan 2026 ➔ Jul 2026

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

GEMINI-Gastric: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=163 | Recruiting | Sponsor: AstraZeneca | N=240 ➔ 163 | Trial completion date: Sep 2027 ➔ May 2029 | Trial primary completion date: Jul 2026 ➔ Nov 2027

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

GEMINI-Gastric: Novel Combinations in Participants With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P2 | N=123 | Sponsor: AstraZeneca | N=17 ➔ 123

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

CLARITY-Gastric 02: a randomised Phase 3 study of sonesitatug vedotin (Sone-Ve) and capecitabine with or without rilvegostomig in Claudin18.2 positive (CLDN18.2+) advanced or metastatic gastric, gastroesophageal junction, or oesophageal adenocarcinoma (GC / GEJC / EAC) (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Gastric Cancer • Oncology • Solid Tumor • CLDN18

AstraZeneca announces strategic equity investment and clinical collaboration with Summit Therapeutics to advance leading ADC combination strategy in cancer (AstraZeneca Press Release) - "Summit and AstraZeneca have also entered into a clinical collaboration agreement to evaluate sonesitatug vedotin (Sone-Ve) in combination with ivonescimab....Under the terms of this agreement, each company will contribute their respective medicine for the planned combination trials and jointly contribute to trial costs....The two companies have also executed a Memorandum of Understanding (MOU) with the intent to enter into an agreement initiating a global development programme combining ivonescimab with AstraZeneca’s cancer medicines, including additional ADCs."

Licensing / partnership • New trial • Gastrointestinal Cancer

Four clinical studies selected for presentation at 2026 ESMO congress: CMG901 (AZD0901) clinical trial results selected as LBA for proffered paper presentation at presidential symposium, MRG007 clinical trial results selected as LBA for rapid oral presentation, and two other studies selected for rapid oral presentation (HKEXnews) - "(1) the Phase III clinical trial of CMG901 in second or later-line (2L+) advanced/metastatic Claudin 18.2-positive gastroesophageal carcinoma ('GEC') has been accepted for presentation as a late-breaking abstract ('LBA') for Proffered Paper presentation at the Presidential Symposium; (2) the Phase I clinical study of MRG007...for the treatment of colorectal cancer ('CRC') has been selected as an LBA for rapid oral presentation; (3) the Phase II study in Europe for the combination therapy of MRG003 and HX008 targeting locally advanced head and neck squamous cell carcinoma ('LA-HNSCC') has been selected for rapid oral presentation; and (4) the Phase II study for the combination therapy of MRG003 and HX008 in epidermal growth factor receptor-positive ('EGFR-positive') unresectable anaplastic/poorly differentiated thyroid cancer has been selected for rapid oral presentation, at the 2026 European Society for Medical Oncology (the 'ESMO') Congress."

Late-breaking abstract • P1 data • P2 data • P3 data • Colorectal Cancer • Gastroesophageal Cancer • Squamous Cell Carcinoma of Head and Neck • Thyroid Gland Carcinoma

CLARITY-Gastric 02: Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in Participants With Advanced or Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma Expressing Claudin18.2 (clinicaltrials.gov) - P3 | N=2130 | Recruiting | Sponsor: AstraZeneca

Trial initiation date • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • CLDN18 • PD-L1

CLDN18.2 dynamics and pharmacodynamic (PD) evaluation in patients (pts) with advanced/metastatic gastric cancer (GC) treated with sonesitatug vedotin (Sone-Ve) in the CLARITY-PT-01 study (ESMO-GI 2026) - P2 | "Conclusions CLDN18.2 staining was consistent between archival and fresh baseline biopsies before Sone-Ve therapy, despite treatments administered between biopsies. Sone-Ve therapy had disparate effects on CLDN18.2 staining; while some patients exhibited stable or decreased staining, a large majority of biopsies remained CLDN18.2 positive."

Clinical • Metastases • PK/PD data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18

A phase 1 trial of claudin 18.2-specific antibody-drug conjugate CMG901 in patients with advanced gastric/gastroesophageal junction cancer (ASCO Plenary Nov 2023) - P1 | "NCT04805307"

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

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

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

Sonesitatug vedotin (Sone-Ve) monotherapy in patients (pts) with claudin 18.2–positive (CLDN18.2+) advanced or metastatic gastric or gastroesophageal junction (GEJ) cancers: Data from CLARITY-PanTumor01. (ASCO 2026) - P2 | "Sone-Ve 2.2 mg/kg demonstrated clinically meaningful efficacy and a manageable safety profile consistent with the first-in-human study. ctDNA MRs were observed in over half the evaluable pts. NC, not calculable."

Clinical • First-in-human • Metastases • Monotherapy • Pan tumor • Gastric Cancer • Oncology • Solid Tumor • CLDN18

MODULE 4: Other Novel Agents and Strategies Under Evaluation for Advanced Gastroesophageal Cancers (ASCO-GI 2026) - "This event is organized and accredited by Research To Practice and supported by educational grants from Astellas, BeOne, Gilead Sciences Inc, and Jazz Pharmaceuticals Inc. Potential immunotherapy targets beyond PD-1/PD-L1 and CTLA-4 in gastroesophageal cancers; proposed rationale for targeting TIGIT Updated efficacy findings, including overall survival outcomes, documented with the combination of the anti-TIGIT monoclonal antibody domvanalimab, the anti-PD-1 antibody zimberelimab and chemotherapy as first-line therapy for advanced gastroesophageal adenocarcinoma in arm A1 of the EDGE-Gastric study Emerging outcomes from the Phase III STAR-221 trial comparing domvanalimab/zimberelimab/chemotherapy to nivolumab/chemotherapy for previously untreated advanced gastric, GEJ and esophageal adenocarcinoma Mechanism of action of and early findings with the PD-1/TIGIT bispecific antibody rilvegostomig for advanced gastroesophageal cancers Ongoing Phase III ARTEMIDE-Gastric01 study..."

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

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

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

GEMINI-Perioperative (PeriOp) Gastric: A phase 2 study of novel agent-based combinations as PeriOp therapy for previously untreated, locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. (ASCO-GI 2026) - P2 | "Background: The standard-of-care treatment for resectable gastric cancer with a high risk of relapse is PeriOp FLOT (5-fluorouracil [5-FU] + leucovorin [isovorin in Japan] + oxaliplatin + docetaxel) and radical surgery. In the MATTERHORN trial, durvalumab + FLOT improved event-free survival versus FLOT alone, establishing a role for immunotherapy + chemotherapy in this setting (Janjigian YY, et al...In substudy 1, CLDN18.2-positive/HER2-negative patients will receive intravenous (IV) sonesitatug vedotin (AZD0901, a CLDN18.2-targeted antibody-drug conjugate) + IV rilvegostomig + 5-FU or capecitabine; in substudy 2, HER2-positive patients will receive IV trastuzumab deruxtecan + IV rilvegostomig + 5-FU or capecitabine; in substudy 3, patients will receive IV rilvegostomig + FLOT...Secondary objectives include the feasibility of surgery, complete resection rate, tumor downstaging, objective response rate, event-free, disease-free, and overall survival, and the..."

Metastases • P2 data • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN18 • HER-2 • PD-L1 • TIGIT

CLARITY-Gastric 01: A randomized phase 3 study of sonesitatug vedotin (sone ve), 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 2026) - P3 | " Participants (pts) will be randomized 1:1:1 to sone ve dose level 1 intravenous (IV) every three weeks (Q3W; Arm 1), sone ve 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-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) (DKK 2026) - P3 | " Patients (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 ESMO - GI Congress 2024, Final Publication Number: 495TiP, Kohei Shitara et al. Reused with permission."

Clinical • Metastases • P3 data • Gastric Cancer • Oncology • Solid Tumor • CLDN18 • HER-2