Sponsor: AstraZeneca (industry)
Phase: 3
Start date: Dec. 4, 2025
Planned enrollment: 1100
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
Goal: Determine whether first-line rilvegostomig plus gemcitabine and cisplatin improves efficacy and has acceptable safety compared with durvalumab plus the same chemotherapy in advanced biliary tract cancer.
Patients: Patients with previously untreated, unresectable locally advanced or metastatic intrahepatic or extrahepatic cholangiocarcinoma or gallbladder adenocarcinoma, measurable disease, known centrally assessed PD-L1 status, and ECOG performance status 0–1. Ampullary carcinoma, prior systemic treatment for advanced disease, prior immune-checkpoint therapy, and certain active autoimmune or inflammatory conditions are excluded.
Design: Global, multicenter, randomized, open-label phase III comparison of two first-line regimens.
Treatments: The experimental arm receives intravenous rilvegostomig with gemcitabine and cisplatin; the comparator receives intravenous durvalumab with the same chemotherapy. Rilvegostomig is an investigational bispecific antibody targeting PD-1 and TIGIT to counter two inhibitory immune pathways. Early single-arm studies in non-small-cell lung cancer have shown antitumor responses, including a 29.0% response rate in checkpoint-inhibitor–naïve patients with PD-L1 TPS 1–49% and 61.8% in those with TPS ≥50%; these findings do not establish benefit in biliary tract cancer or superiority over durvalumab. Durvalumab is a PD-L1 inhibitor used with gemcitabine and cisplatin as a first-line regimen for advanced biliary tract cancer.
Outcomes: The primary endpoint is overall survival in patients with PD-L1 expression ≥1%. Secondary endpoints include overall survival in the intention-to-treat population; progression-free survival, objective response, duration of response, and time to second progression or death in both populations; adverse events; rilvegostomig pharmacokinetics and antidrug antibodies; and patient-reported pain and global health status/quality of life.
Burden on patient: Estimated moderate burden. Both arms require intravenous immunotherapy and chemotherapy visits, repeated CT or MRI scans, and safety assessments typical of intensive first-line treatment. Central PD-L1 testing requires an acceptable tumor sample, but a new biopsy is not specified. Additional pharmacokinetic and immunogenicity blood sampling, questionnaires, and follow-up after progression may add visits or time compared with routine care.
Last updated: Sep 2026
Key inclusion Criteria:
* Histologically confirmed adenocarcinoma of the biliary tract, including intra-hepatic or extra-hepatic cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC).
* Unresectable locally advanced or metastatic BTC, previously untreated in the advanced disease setting
* Known PD-L1 status assessed at a central laboratory using an acceptable tumor sample.
* Measurable disease by RECIST 1.1 criteria using CT or MRI and is suitable for accurate repeated measurements.
* ECOG Performance Status of 0 or 1 with no deterioration (ie, ECOG PS \> 1) over the previous 2 weeks prior to baseline at screening and prior to randomization.
* Adequate bone marrow and organ function.
Key exclusion Criteria:
* Ampullary carcinoma
* Any prior systemic therapy received for unresectable, locally advanced or metastatic BTC.
* Any prior exposure to any other therapy targeting immune-regulatory receptors or mechanisms.
* Any concurrent chemotherapy, radiotherapy, immunotherapy, investigational, biologic, or hormonal therapy for cancer treatment other than those under investigation in this study.
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* Active or ongoing interstitial lung disease/pneumonitis (of any grade), serious chronic gastrointestinal conditions associated with diarrhea, or active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment.
Darlinghurst, 2010, Australia
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Vitória, 29043-272, Brazil
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Porto Alegre, 91350-200, Brazil
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Natal, 59075-740, Brazil
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Barretos, 14784-400, Brazil
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São Paulo, 01246-000, Brazil
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Halifax, Nova Scotia, B3H 2Y9, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Fuzhou, 350005, China
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Hefei, 230001, China
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Changde, 415000, China
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Takatsuki-shi, 569-8686, Japan
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Ube, 755-8505, Japan
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Yokohama, 241-8515, Japan
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Chiba, 260-8717, Japan
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Kōtoku, 135-8550, Japan
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Matsuyama, 790-0024, Japan
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Suita-shi, 565-0871, Japan
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Seoul, 03080, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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Busan, 48108, South Korea
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Seongnam-si, 13620, South Korea
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Taichung, 40705, Taiwan
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Kaohsiung City, 82445, Taiwan
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Kaohsiung City, 833, Taiwan
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Taichung, 40447, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 112, Taiwan
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Taoyuan District, 333, Taiwan
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Khon Kaen, 40002, Thailand
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Chiang Mai, 50200, Thailand
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Duarte, California, 91010, United States
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Marietta, Georgia, 30060, United States
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Santa Fe, New Mexico, 87505, United States
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Sioux Falls, South Dakota, 57105, United States
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Murdoch, 6150, Australia
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Gosford, 2250, Australia
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Anderlecht, 1070, Belgium
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Roeselare, 8800, Belgium
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Liège, 4000, Belgium
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Leuven, 3000, Belgium
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Edegem, 2650, Belgium
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Ribeirão Preto, 14026-040, Brazil
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Calgary, Alberta, T2N 5G2, Canada
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Vancouver, British Columbia, VSZ 4E6, Canada
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Barrie, Ontario, L4M 6M2, Canada
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Québec, Quebec, G1J 1Z4, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Xi'an, 710061, China
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Wuhan, 430030, China
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Weifang, 261000, China
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Shenyang, 110016, China
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Shanghai, 200032, China
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Shandong, China
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Nanning, 530000, China
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Nanchang, 330000, China
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Luoyang, 471023, China
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Hangzhou, 310022, China
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Beijing, 100020, China
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Beijing, 102218, China
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Changchun, 130021, China
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Changsha, 410005, China
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Chengdu, 610078, China
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Guangzhou, 510515, China
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Clichy, 92118, France
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Grenoble, 38043, France
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Marseille, 13385, France
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Vandœuvre-lès-Nancy, 54511, France
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Hamburg, 20249, Germany
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Hamburg, 22763, Germany
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Heidelberg, 69120, Germany
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Heilbronn, 74078, Germany
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Karlsruhe, 76133, Germany
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Magdeburg, 39120, Germany
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München, 81737, Germany
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Ulm, 89081, Germany
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Aachen, 52074, Germany
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Berlin, 10365, Germany
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Berlin, 13353, Germany
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Düsseldorf, 40225, Germany
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Bonn, 53127, Germany
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Essen, 45122, Germany
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Frankfurt, 60488, Germany
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Freiburg im Breisgau, 79106, Germany
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Delhi, 110029, India
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Hyderabad, 500032, India
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Kolhāpur, 416234, India
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Kolkata, 700063, India
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Mumbai, 400012, India
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Nashik, 422002, India
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Surat, 395002, India
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Rome, 00168, Italy
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Pisa, 56126, Italy
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Milan, 20132, Italy
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Castellana Grotte, 70013, Italy
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Rozzano, 20089, Italy
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Kawasaki-shi, 216-8511, Japan
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Kashiwa, 227-8577, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Osaka, 541-8567, Japan
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Amsterdam, 1081 HV, Netherlands
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Utrecht, 3584 CX, Netherlands
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Maastricht, 6202 AZ, Netherlands
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Groningen, 9713 GZ, Netherlands
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Warsaw, 02-034, Poland
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Olsztyn, 10-228, Poland
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Koszalin, 75-581, Poland
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Lodz, 92-213, Poland
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Krakow, 30-688, Poland
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Seoul, 06591, South Korea
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Daegu, 41404, South Korea
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Seongnam-si, 13496, South Korea
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Seoul, 03722, South Korea
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Santander, 39008, Spain
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Madrid, 28040, Spain
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Madrid, 28007, Spain
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L'Hospitalet de Llobregat, 08908, Spain
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Barcelona, 08036, Spain
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Muang, 34000, Thailand
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Ongkharak, 26120, Thailand
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Bangkok, 10700, Thailand
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Hat Yai, 90110, Thailand
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Seyhan, 1060, Turkey (Türkiye)
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Konya, 42080, Turkey (Türkiye)
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Status: Not yet recruiting
Ankara, 06100, Turkey (Türkiye)
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Status: Not yet recruiting
Erzurum, 25240, Turkey (Türkiye)
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Status: Not yet recruiting
Istanbul, 34010, Turkey (Türkiye)
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Status: Not yet recruiting
Manchester, M20 4BX, United Kingdom
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Status: Not yet recruiting
Birmingham, B15 2GW, United Kingdom
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Glasgow, G12 OYN, United Kingdom
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Greater London, SW3 6JJ, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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London, NW3 2QG, United Kingdom
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Birmingham, Alabama, 35233, United States
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Status: Not yet recruiting
Phoenix, Arizona, 85054, United States
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Status: Not yet recruiting
Tucson, Arizona, 85719, United States
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Status: Not yet recruiting
Santa Monica, California, 90404, United States
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Status: Not yet recruiting
Orange, California, 92868, United States
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Status: Not yet recruiting
Stanford, California, 94305-5847, United States
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Aurora, Colorado, 80045, United States
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Status: Not yet recruiting
Hartford, Connecticut, 06102, United States
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New Haven, Connecticut, 06510, United States
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Washington D.C., District of Columbia, 20037, United States
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Washington D.C., District of Columbia, 20007, United States
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Jacksonville, Florida, 32209, United States
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Jacksonville, Florida, 32224, United States
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Chicago, Illinois, 60612, United States
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Chicago, Illinois, 60637, United States
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Status: Not yet recruiting
Louisville, Kentucky, 40207, United States
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Status: Not yet recruiting
Baltimore, Maryland, 21205, United States
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Status: Not yet recruiting
Ann Arbor, Michigan, 48109, United States
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Status: Not yet recruiting
Detroit, Michigan, 48202, United States
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Status: Not yet recruiting
Rochester, Minnesota, 55905, United States
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Status: Not yet recruiting
Omaha, Nebraska, 68198-5885, United States
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Status: Not yet recruiting
New York, New York, 10032, United States
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Status: Not yet recruiting
New York, New York, 10016, United States
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Status: Not yet recruiting
Portland, Oregon, 97239, United States
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Pittsburgh, Pennsylvania, 15212, United States
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Philadelphia, Pennsylvania, 19111, United States
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Philadelphia, Pennsylvania, 19104, United States
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Providence, Rhode Island, 02903, United States
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Status: Not yet recruiting
Lishui, 323000, China
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Status: Withdrawn
New York, New York, 10065, United States
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Status: Withdrawn
Changsha, 410013, China
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Status: SUSPENDED