Sponsor: AstraZeneca (industry)
Phase: 3
Start date: Feb. 3, 2026
Planned enrollment: 2130
Rilvegostomig (AZD2936) is an investigational bispecific immune-checkpoint antibody being developed for solid tumors, most extensively studied in non-small-cell lung cancer (NSCLC). Clinical evidence remains preliminary and largely comes from the nonrandomized phase I/II ARTEMIDE-01 trial; randomized phase III NSCLC studies are ongoing. (pubmed.ncbi.nlm.nih.gov)
Rilvegostomig is a humanized IgG1 antibody that simultaneously targets PD-1 and TIGIT, inhibitory receptors found on T cells and natural killer cells. Dual blockade is intended to restore antitumor immune activity more effectively than inhibition of either pathway alone. Its Fc region contains three mutations designed to minimize Fc-mediated immune-effector activity. (ascopubs.org)
In checkpoint-inhibitor–experienced, PD-L1-positive advanced NSCLC, ARTEMIDE-01 established 750 mg intravenously every three weeks as the recommended phase II dose. Among patients treated at this dose, the objective response rate (ORR) was 5.6%, the six-month disease-control rate was 31.5%, and median progression-free survival (PFS) was 3.8 months. (pubmed.ncbi.nlm.nih.gov)
Updated results in 65 checkpoint-inhibitor–naïve patients receiving 750 mg every three weeks showed:
These single-arm results cannot establish whether rilvegostomig is superior to currently available checkpoint inhibitors. (annalsofoncology.org)
In 83 checkpoint-inhibitor–experienced patients, 54.2% experienced a treatment-related adverse event, including 8.4% with grade 3 events; no dose-limiting toxicities were observed, and 2.4% discontinued because of treatment-related toxicity. Immune-mediated adverse events occurred in 18.1%. (pubmed.ncbi.nlm.nih.gov)
Among the 65 checkpoint-inhibitor–naïve patients in the later analysis, grade 3 treatment-related adverse events occurred in 12.3%, treatment-related discontinuations in 3.1%, and no grade 4 or 5 treatment-related events were reported. (annalsofoncology.org)
Last updated: Sep 2026
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)
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)
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)
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)
Last updated: Sep 2026
Goal: Evaluate whether first-line sonesitatug vedotin plus capecitabine, with or without an immune-checkpoint inhibitor, improves outcomes in CLDN18.2-positive, HER2-negative advanced gastroesophageal adenocarcinoma while assessing safety and diagnostic test performance.
Patients: Adults with previously untreated, unresectable locally advanced or metastatic gastric, gastroesophageal junction, or distal esophageal adenocarcinoma; centrally confirmed CLDN18.2 positivity and PD-L1 status; ECOG performance status 0–1; and adequate organ function. Cohort 1 includes PD-L1-positive, checkpoint-inhibitor-eligible patients. Cohort 2 includes PD-L1-negative or checkpoint-inhibitor-ineligible patients.
Design: Multicentre, randomized controlled trial with two cohorts assigned according to PD-L1 status and checkpoint-inhibitor eligibility. Investigational regimens are compared with active treatment regimens appropriate to each cohort.
Treatments: Cohort 1 evaluates sonesitatug vedotin plus capecitabine with either rilvegostomig or nivolumab, against nivolumab plus CAPOX or FOLFOX. Cohort 2 evaluates sonesitatug vedotin plus capecitabine against zolbetuximab plus CAPOX or FOLFOX, or CAPOX or FOLFOX alone. Sonesitatug vedotin is a CLDN18.2-directed antibody–drug conjugate that delivers the microtubule-disrupting agent MMAE into target cells. Single-arm studies in previously treated gastric or gastroesophageal junction cancer reported response rates of approximately 28%; those results do not establish first-line benefit. Rilvegostomig is an investigational bispecific antibody blocking PD-1 and TIGIT to enhance antitumor immune activity. Early single-arm lung cancer studies reported responses, but have not established superiority over available checkpoint inhibitors or efficacy in this disease. Nivolumab is a PD-1 inhibitor; zolbetuximab targets CLDN18.2; CAPOX and FOLFOX are oxaliplatin-based chemotherapy regimens.
Outcomes: Primary endpoints are RECIST 1.1 progression-free survival in both cohorts and overall survival in cohort 1. Secondary measures include cohort 2 overall survival, additional cohort 1 comparisons of nivolumab-containing arms, objective response rate, duration of response, adverse events, and pharmacokinetics and immunogenicity of the investigational drugs. Outcomes may be assessed for up to approximately five years.
Burden on patient: Moderate. Central CLDN18.2 and PD-L1 testing is required, and participants will need treatment visits, repeated imaging and safety assessments, and blood draws for pharmacokinetics and immunogenicity. Intravenous combination regimens and long-term follow-up add travel and monitoring compared with routine oral therapy. The protocol information provided does not specify imaging or blood-draw frequency or require additional research biopsies.
Last updated: Sep 2026
Inclusion Criteria:
* Capable of giving signed informed consent
* Participant must be 18 years or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the informed consent.
* Previously untreated histologically documented unresectable, locally advanced, or metastatic gastric, GEJ, or distal esophagus (distal third of the esophagus) adenocarcinoma
* Positive CLDN18.2 expression, as determined prospectively by central IHC testing
* Confirmed PD-L1 CPS status by central IHC testing and ICI eligibility per investigator judgement is required to determine cohort eligibility as described below:
1. Cohort 1: PD-L1 positive as determined by central IHC testing and the participant is deemed ICI eligible per investigator judgement.
2. Cohort 2: PD-L1 negative as determined by central IHC testing OR the participant is ICI ineligible
* ECOG performance status of 0 or 1 with no deterioration to \> 1 over the previous 2 weeks prior to baseline at screening and prior to randomisation.
* Minimum life expectancy of ≥ 12 weeks.
* At least one lesion (measurable and/or non-measurable) that can be accurately assessed by the investigator based on RECIST 1.1.
* Adequate organ and bone marrow function as specified in the protocol
* Body weight ≥ 35 kg.
* Sex and contraceptive requirements
Exclusion Criteria:
* Known HER2-positive status
* Significant or unstable gastric bleeding and/or untreated gastric ulcers.
* Active or history of autoimmune or inflammatory disorders requiring systemic treatment with steroids or other immunosuppressive treatment or assessed by investigator as not appropriate to participate due to undue risk are excluded.
* CNS pathology
* Clinically significant pleural effusions or ascites and/or pleural effusions or ascites that require drainage, peritoneal shunt, or indwelling catheter/drain.
* Require parenteral nutrition support due to gastric or gastrointestinal obstruction.
* Peripheral neuropathy, sensory or motor, ≥ CTCAE Grade 2 at screening.
* Persistent toxicities caused by previous anticancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.
* Cardiac abnormalities as outlined in the protocol
* Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomisation.
* Infectious disease including active hepatitis A infection; uncontrolled hepatitis B and/or chronic or active hepatitis B with HBV DNA ≥ 100 IU/mL; Known chronic, active, or uncontrolled hepatitis C; HIV infection that is not well controlled
* Known partial or total DPD enzyme deficiency
Westmead, 2145, Australia
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Randwick, 2031, Australia
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Murdoch, 6150, Australia
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Brampton, Ontario, L6R 3J7, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Québec, Quebec, G1J 1Z4, Canada
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Montreal, Quebec, H3A 1A1, Canada
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Beijing, 100032, China
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Beijing, 100142, China
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Kashiwa, 277-8577, Japan
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Kaohsiung City, 80756, Taiwan
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Taoyuan District, 333, Taiwan
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Taipei, 112, Taiwan
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Taichung, 40705, Taiwan
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Taichung, 40447, Taiwan
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Kaohsiung City, 83301, Taiwan
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Grand Rapids, Michigan, 49503, United States
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East Brunswick, New Jersey, 08816, United States
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Nashville, Tennessee, 37203, United States
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Heidelberg, 3084, Australia
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Edegem, 2650, Belgium
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Brussels, 1200, Belgium
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Leuven, 3000, Belgium
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Ghent, 9000, Belgium
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Vitória, 29043-260, Brazil
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Santa Maria, 97015-450, Brazil
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Salvador, 41.950-610, Brazil
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Porto Alegre, 91350200, Brazil
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Natal, 59075-740, Brazil
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Fortaleza, 60336-045, Brazil
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Barretos, 14784-400, Brazil
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São Paulo, 01246-000, Brazil
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Edmonton, Alberta, T6G 1Z2, Canada
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Vancouver, British Columbia, VSZ 4E6, Canada
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Abbotsford British Columbia, British Columbia, V2S0C2, Canada
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Moncton, New Brunswick, E1C 2Z3, Canada
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Sault Ste. Marie, Ontario, P6A 0A8, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Harbin, 150081, China
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Beijing, 100050, China
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Beijing, 102200, China
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Changde, 415000, China
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Chengdu, 610041, China
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Chongqing, 400016, China
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Fuzhou, 350005, China
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Fuzhou, 350011, China
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Guangzhou, 510655, China
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Hangzhou, 310003, China
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Hangzhou, 310014, China
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Hangzhou, 310020, China
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Hefei, 230031, China
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Hohhot, 010020, China
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Jinan, 2501117, China
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Kunming, 650118, China
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Lanzhou, 730000, China
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Linhai, 317000, China
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Linyi, 276000, China
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Nanchang, 330000, China
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Nanchang, 330029, China
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Nanjing, 2100008, China
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Nanjing, 210029, China
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Nanning, 530021, China
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Nantong, 226361, China
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Shanghai, 200025, China
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Shanghai, 200127, China
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Shanghai, 20032, China
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Shantou, 515041, China
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Shenyang, 110016, China
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Shenzhen, 518036, China
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Tianjin, 300050, China
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Wuhan, 430030, China
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Wuhan, 430079, China
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Xi'an, 710068, China
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Xiamen, 361003, China
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Xingtai, 054031, China
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Xuzhou, 221009, China
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Yinchuan, 750004, China
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Zhengzhou, 450008, China
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Lyon, 69373, France
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Caen, 41076, France
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Bordeaux, 33000, France
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Marseille, 13273, France
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Rennes, 35000, France
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Villejuif, 94805, France
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Mainz, 55131, Germany
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Moers, 47441, Germany
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München, 81657, Germany
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Stuttgart, 70376, Germany
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Ulm, 89081, Germany
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Frankfurt, 60488, Germany
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Freiburg im Breisgau, 79106, Germany
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Hamburg, 20249, Germany
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Heilbronn, 74078, Germany
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Leipzig, 04103, Germany
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Essen, 45122, Germany
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Bonn, 53127, Germany
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Berlin, 13353, Germany
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Augsburg, 86156, Germany
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Budapest, 1122, Hungary
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Budapest, 1083, Hungary
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Nyíregyháza, 4400, Hungary
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Gyula, 5700, Hungary
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Pécs, 7624, Hungary
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Zalaegerszeg, 8900, Hungary
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Győr, 9024, Hungary
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Debrecen, 4032, Hungary
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Mumbai, 400012, India
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Vijayawada, 520002, India
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New Delhi, 110017, India
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Mohali, 160055, India
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Hyderabad, 500032, India
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Bhubaneswar, 751019, India
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Ahmedabad, 380060, India
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Padova, 35128, Italy
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Milan, 20162, Italy
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Milan, 20141, Italy
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Milan, 20133, Italy
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Meldola, 47014, Italy
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Tricase, 73039, Italy
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Rozzano, 20089, Italy
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Hirakata-shi, 573-1191, Japan
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Chūōku, 104-0045, Japan
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Nagoya, 464-8681, Japan
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Kitaadachi-gun, 362-0806, Japan
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Kōtoku, 135-8550, Japan
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Kurashiki-shi, 710-8602, Japan
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Niigata, 951-8566, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Sakai, 590-0197, Japan
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Sendai, 980-8574, Japan
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Sunto-gun, 411-8777, Japan
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Status: Not yet recruiting
Yokohama, 232-0024, Japan
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Yokohama, 241-8515, Japan
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Status: Not yet recruiting
Rotterdam, 3015 GD, Netherlands
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Tilburg, 5022 GC, Netherlands
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Groningen, 9713 GZ, Netherlands
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Status: Not yet recruiting
Gdansk, 80-219, Poland
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Status: Not yet recruiting
Koszalin, 75-581, Poland
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Status: Not yet recruiting
Krakow, 31-501, Poland
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Lublin, 20-080, Poland
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Olsztyn, 10-228, Poland
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Warsaw, 02-034, Poland
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San Juan, 00921, Puerto Rico
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Seoul, 06591, South Korea
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Seoul, 06351, South Korea
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Status: Not yet recruiting
Seoul, 05505, South Korea
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Status: Not yet recruiting
Seoul, 03722, South Korea
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Seoul, 03080, South Korea
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Seongnam-si, 13620, South Korea
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Daegu, 41404, South Korea
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Hwasun-gun, 58128, South Korea
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Barcelona, 8036, Spain
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Barcelona, 08035, Spain
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Madrid, 28041, Spain
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Pamplona, 31008, Spain
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Santander, 39008, Spain
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Santiago de Compostela, 15706, Spain
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Valencia, 46010, Spain
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Taipei, 10002, Taiwan
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Tainan, 704, Taiwan
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Muang, 22000, Thailand
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Khon Kaen, 40002, Thailand
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Hat Yai, 90110, Thailand
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Dusit, 10300, Thailand
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Bangkok, 10700, Thailand
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Bangkok, 10210, Thailand
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Muang, 70000, Thailand
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Medreseboğazı, 01250, Turkey (Türkiye)
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Istanbul, 34854, Turkey (Türkiye)
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Istanbul, 34098, Turkey (Türkiye)
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Antalya, 07100, Turkey (Türkiye)
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Ankara, 06530, Turkey (Türkiye)
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Şahinbey, 27310, Turkey (Türkiye)
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Cambridge, CB2 0QQ, United Kingdom
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Oxford, OX3 7LE, United Kingdom
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Manchester, M20 4BX, United Kingdom
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London, EC1A 7BE, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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Dundee, DD1 9SY, United Kingdom
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Phoenix, Arizona, 85054, United States
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Springdale, Arkansas, 72762, United States
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Orange, California, 92868, United States
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Duarte, California, 91010, United States
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La Jolla, California, 92093, United States
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Los Alamitos, California, 90720, United States
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Walnut Creek, California, 94598, United States
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Lone Tree, Colorado, 80124, United States
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Denver, Colorado, 80210, United States
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Newark, Delaware, 19713, United States
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Jacksonville, Florida, 32224, United States
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Macon, Georgia, 31201, United States
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Atlanta, Georgia, 30322, United States
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Atlanta, Georgia, 30309, United States
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Newnan, Georgia, 30265, United States
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Chicago, Illinois, 60637, United States
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Niles, Illinois, 60714, United States
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Zion, Illinois, 60099, United States
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Indianapolis, Indiana, 46260, United States
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Waukee, Iowa, 50263, United States
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Lexington, Kentucky, 40536, United States
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Louisville, Kentucky, 40207, United States
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Burlington, Massachusetts, 01803, United States
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Boston, Massachusetts, 02114, United States
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Burnsville, Minnesota, 55337, United States
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Rochester, Minnesota, 55905, United States
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Kansas City, Missouri, 64132, United States
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St Louis, Missouri, 63110, United States
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Hackensack, New Jersey, 07601, United States
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Status: Not yet recruiting
Camden, New Jersey, 08103, United States
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Status: Not yet recruiting
Summit, New Jersey, 07901, United States
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New York, New York, 10065, United States
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New York, New York, 10032, United States
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The Bronx, New York, 10461, United States
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The Bronx, New York, 10468, United States
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Winston-Salem, North Carolina, 27103, United States
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Columbus, Ohio, 43221, United States
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Portland, Oregon, 97239, United States
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Portland, Oregon, 97213, United States
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Wilkes-Barre, Pennsylvania, 18711, United States
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Hershey, Pennsylvania, 17033, United States
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Philadelphia, Pennsylvania, 19104, United States
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Pittsburgh, Pennsylvania, 15232, United States
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Pittsburgh, Pennsylvania, 15240, United States
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Status: Not yet recruiting
Sioux Falls, South Dakota, 57105, United States
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Status: Not yet recruiting
Dallas, Texas, 75246, United States
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Status: Not yet recruiting
Sherman, Texas, 75090, United States
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Status: Not yet recruiting
Blacksburg, Virginia, 24060, United States
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Status: Not yet recruiting
Fairfax, Virginia, 22031, United States
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Status: Not yet recruiting
Fort Belvoir, Virginia, 22060, United States
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Status: Not yet recruiting
Richmond, Virginia, 23219, United States
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Status: Not yet recruiting
Seattle, Washington, 98104, United States
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Status: Not yet recruiting
Olympia, Washington, 98502, United States
No email / No phone
Status: Not yet recruiting
Charleston, West Virginia, 25315, United States
No email / No phone
Status: Not yet recruiting
Milwaukee, Wisconsin, 53226, United States
No email / No phone
Status: Not yet recruiting
Rankweil, 6830, Austria
No email / No phone
Status: Withdrawn
Linz, 4010, Austria
No email / No phone
Status: Withdrawn
Wiener Neustadt, 2700, Austria
No email / No phone
Status: Withdrawn
Vienna, 1090, Austria
No email / No phone
Status: Withdrawn
Winnipeg, Manitoba, R3E 0V9, Canada
No email / No phone
Status: Withdrawn
Mannheim, 68167, Germany
No email / No phone
Status: Withdrawn
Heidelberg, 69120, Germany
No email / No phone
Status: Withdrawn
Varanasi, 221005, India
No email / No phone
Status: Withdrawn
New Delhi, 110060, India
No email / No phone
Status: Withdrawn
New Haven, Connecticut, 06510, United States
No email / No phone
Status: Withdrawn
Washington D.C., District of Columbia, 20007, United States
No email / No phone
Status: Withdrawn
St. Petersburg, Florida, 33705, United States
No email / No phone
Status: Withdrawn
West Palm Beach, Florida, 33401, United States
No email / No phone
Status: Withdrawn
Fort Myers, Florida, 33901, United States
No email / No phone
Status: Withdrawn
Atlanta, Georgia, 30342, United States
No email / No phone
Status: Withdrawn
New York, New York, 10029, United States
No email / No phone
Status: Withdrawn
White Plains, New York, 10601, United States
No email / No phone
Status: Withdrawn
Cleveland, Ohio, 44195, United States
No email / No phone
Status: Withdrawn
Memphis, Tennessee, 38104, United States
No email / No phone
Status: Withdrawn
Falls Church, Virginia, 22042, United States
No email / No phone
Status: Withdrawn
Darlinghurst, 2010, Australia
No email / No phone
Status: SUSPENDED
Garran, 2605, Australia
No email / No phone
Status: SUSPENDED