Sponsor: AstraZeneca (industry)
Phase: 3
Start date: Nov. 27, 2024
Planned enrollment: 878
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 platinum-based chemotherapy improves efficacy compared with pembrolizumab plus the same chemotherapy in PD-L1–positive metastatic non-squamous NSCLC, while assessing safety.
Patients: Patients with untreated stage IV non-squamous NSCLC, tumor PD-L1 expression in at least 1% of tumor cells, measurable disease, and adequate organ function. Patients with sensitizing EGFR mutations, ALK or ROS1 rearrangements, or other actionable drivers with locally approved first-line targeted therapies are excluded. Stable, asymptomatic brain metastases are permitted under specified conditions.
Design: Global, multicenter, randomized, double-blind, two-arm trial comparing two first-line chemoimmunotherapy regimens. Follow-up for key outcomes extends to approximately five years.
Treatments: Both groups receive pemetrexed plus cisplatin or carboplatin, combined with either rilvegostomig or pembrolizumab; maintenance consists of pemetrexed with the assigned immunotherapy. Rilvegostomig is an investigational bispecific antibody targeting PD-1 and TIGIT to counter inhibitory immune signaling. In a preliminary single-arm study of checkpoint-inhibitor–naïve advanced NSCLC, reported response rates were 29.0% for PD-L1 expression of 1–49% and 61.8% for expression of at least 50%; these results do not establish comparative benefit. Pembrolizumab is an established PD-1 inhibitor used with platinum–pemetrexed chemotherapy in this setting.
Outcomes: Primary endpoints are overall survival and RECIST 1.1 progression-free survival. Secondary measures include landmark survival rates, time to second progression or death, response rate and duration, rilvegostomig pharmacokinetics and immunogenicity, and patient-reported physical function, quality of life, and lung cancer symptoms.
Burden on patient: Estimated moderate burden. Both arms involve recurring intravenous chemoimmunotherapy and maintenance visits, imaging to assess disease, and routine safety monitoring, broadly consistent with intensive standard first-line treatment. Trial-specific requirements include a suitable tumor sample, blood sampling for drug concentrations and antidrug antibodies, and patient questionnaires; multicenter visits may also require travel. The schedule and whether a new biopsy is necessary are not specified.
Last updated: Sep 2026
Inclusion Criteria:
* Histologically or cytologically documented non-squamous NSCLC.
* Stage IV mNSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment.
* Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements.
* Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted 1L therapies.
* Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC ≥ 1%.
* At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements.
* Adequate organ and bone marrow function
Exclusion Criteria:
* Presence of small cell and neuroendocrine histology components.
* Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization.
* Any prior systemic therapy received for advanced or mNSCLC. Prior systemic therapy in the neoadjuvant or adjuvant setting and/or definitive radio- or chemoradiotherapy for early-stage disease are allowed, provided that recurrence or progression has occurred \> 12 months after the end of treatment.
* Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
* Any prior treatment with an anti-PD-1 or anti-PD-L1 agent.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* Active primary immunodeficiency/active infectious disease(s).
* Active tuberculosis infection.
Buenos Aires, C1431FWO, Argentina
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CABA, 1425, Argentina
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Pilar, B1629ODT, Argentina
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Rosario, S2000DEJ, Argentina
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Darlinghurst, 2010, Australia
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Hyde Park, 4812, Australia
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Southport, 4215, Australia
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Wollongong, 2500, Australia
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Brussels, 1160, Belgium
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Charleroi, 6060, Belgium
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Kortrijk, 8500, Belgium
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Ottignies, 1340, Belgium
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Ijuí, 98700-000, Brazil
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Londrina, 86015-520, Brazil
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Passo Fundo, 99010-260, Brazil
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Porto Alegre, 91350-200, Brazil
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Salvador, 40050 410, Brazil
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São Paulo, 01327-001, Brazil
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São Paulo, 05652000, Brazil
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Vitória, 29043-260, Brazil
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Saint John, New Brunswick, E2L 4L2, Canada
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Hamilton, Ontario, L8V 1C3, Canada
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Kingston, Ontario, K7L 2V7, Canada
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Sault Ste. Marie, Ontario, P6A 0A8, Canada
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Saint-Jérôme, Quebec, J7Z 2V4, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Montreal, Quebec, H2X 0A9, Canada
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Zhengzhou, 450052, China
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Beijing, 100029, China
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Beijing, CN-100730, China
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Changchun, 130012, China
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Chengdu, 610041, China
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Chongqing, 400030, China
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Fuzhou, 350007, China
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Guangzhou, 510062, China
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Guangzhou, 510180, China
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Hangzhou, 310003, China
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Hangzhou, 310016, China
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Hangzhou, 310022, China
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Harbin, 150081, China
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Hefei, 230601, China
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Jingzhou, 434000, China
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Kunming, 650118, China
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Linhai, 317000, China
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Nanchang, 330008, China
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Ningbo, 315010, China
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Shanghai, 200030, China
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Wenzhou, CN-325000, China
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Wuhan, 430000, China
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Xi'an, 710061, China
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Xiangyang, 441000, China
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Beijing, 100021, China
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Zhengzhou, 450008, China
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Suresnes, 92150, France
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Avignon, 84902, France
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La Rochelle, 17019, France
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Lyon, 69373, France
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Nîmes, 30029, France
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Rennes, 35033, France
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Strasbourg, 67091, France
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Toulon, 83800, France
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Krefeld, 47805, Germany
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Kiel, 24105, Germany
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Kassel, 34125, Germany
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Homburg, 66424, Germany
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Würzburg, 97067, Germany
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Hemer, 58675, Germany
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Hanover, 30625, Germany
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Hanover, 30459, Germany
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Hamburg, 20251, Germany
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Großhansdorf, 22927, Germany
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Giessen, 35392, Germany
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Gauting, 82131, Germany
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Frankfurt, 60488, Germany
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Esslingen am Neckar, 73730, Germany
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Cologne, 51109, Germany
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Berlin, 13585, Germany
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Bad Berka, 99437, Germany
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Regensburg, 93053, Germany
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Moers, 47441, Germany
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Minden, 32429, Germany
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Gyöngyös - Mátraháza, 3200, Hungary
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Debrecen, 4032, Hungary
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Pécs, 7624, Hungary
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Törökbálint, 2045, Hungary
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Budapest, 1122, Hungary
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Budapest, 1121, Hungary
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Győr, 9024, Hungary
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Delhi, 110029, India
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Madurai, 625107, India
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Nashik, 422002, India
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Varanasi, 221005, India
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Calicut, 673601, India
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Florence, 50134, Italy
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Monza, 20052, Italy
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Peschiera del Garda, 37019, Italy
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Rome, 00168, Italy
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Yokohama, 241-8515, Japan
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Amagasaki-shi, 660-8550, Japan
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Bunkyō City, 113-8603, Japan
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Chūōku, 104-0045, Japan
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Fukuoka, 812-8582, Japan
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Fukuoka, 814-0180, Japan
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Hiroshima, 734-8551, Japan
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Kawagoe-shi, 350-8550, Japan
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Kawasaki-shi, 216-8511, Japan
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Kitaadachi-gun, 362-0806, Japan
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Kitakyushu-shi, 807-8555, Japan
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Kobe, 650-0017, Japan
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Kōtoku, 135-8550, Japan
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Kumamoto, 860-8556, Japan
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Kumamoto, 861-4193, Japan
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Matsusaka-shi, 515-8544, Japan
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Osaka, 541-8567, Japan
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Ota-shi, 373-8550, Japan
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Saitama-shi, 338-0001, Japan
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Sendai, 981-0914, Japan
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Shinjuku-ku, 160-0023, Japan
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Sunto-gun, 411-8777, Japan
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Takaoka-shi, 933-8555, Japan
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Yokohama, 232-0024, Japan
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Kuching, 93586, Malaysia
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Petaling Jaya, 47500, Malaysia
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Kuala Lumpur, 59100, Malaysia
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Alkmaar, 1815 JD, Netherlands
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Ede, 6716 RP, Netherlands
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Leidschendam, 2262 BA, Netherlands
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Veldhoven, 5504 DB, Netherlands
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Bystra, 43-360, Poland
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Poznan, 60-569, Poland
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Lodz, 93-338, Poland
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San Juan, 00935, Puerto Rico
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Songpa-gu, 05505, South Korea
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Seoul, 07061, South Korea
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Gyeonggi-do, 13620, South Korea
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Madrid, 28046, Spain
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Barcelona, 8035, Spain
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Castellon, 12002, Spain
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Las Palmas de Gran Canaria, 35016, Spain
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Madrid, 28034, Spain
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Majadahonda, 28222, Spain
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Seville, 41013, Spain
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Kaohsiung City, 80756, Taiwan
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Taoyuan District, 333423, Taiwan
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Tainan, 736, Taiwan
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Taichung, 40705, Taiwan
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Taichung, 40201, Taiwan
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New Taipei City, 23561, Taiwan
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New Taipei City, 220, Taiwan
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Kaohsiung City, 824, Taiwan
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Bangkok, 10700, Thailand
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Songkhla, 90110, Thailand
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Nakhon Ratchasima, 30000, Thailand
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Dusit, 10300, Thailand
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Chiang Mai, 50200, Thailand
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Antalya, 07070, Turkey (Türkiye)
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Ankara, 06010, Turkey (Türkiye)
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Seyhan, 1060, Turkey (Türkiye)
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Izmir, 35965, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Antalya, 07100, Turkey (Türkiye)
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Manchester, M20 4BX, United Kingdom
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London, SE1 9RT, United Kingdom
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London, EC1A 7BE, United Kingdom
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Greater London, SW3 6JJ, United Kingdom
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Edinburgh, EH4 2XU, United Kingdom
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Cambridge, CB2 0QQ, United Kingdom
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Aberdeen, AB25 2ZN, United Kingdom
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Torquay, TQ2 7AA, United Kingdom
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Newcastle upon Tyne, NE7 7AF, United Kingdom
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Mobile, Alabama, 36608, United States
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Phoenix, Arizona, 85054, United States
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Redlands, California, 92373, United States
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Anaheim, California, 92801, United States
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Beverly Hills, California, 90211, United States
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San Diego, California, 92123, United States
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San Francisco, California, 94121, United States
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Santa Rosa, California, 95403, 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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Stamford, Connecticut, 06902, United States
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West Haven, Connecticut, 06516, United States
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Newark, Delaware, 19713, United States
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Bay Pines, Florida, 33744, United States
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St. Petersburg, Florida, 33709, United States
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Miami, Florida, 33125, United States
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Jacksonville, Florida, 32224, United States
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Fort Lauderdale, Florida, 33308, United States
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Boise, Idaho, 83712, United States
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Decatur, Illinois, 62526, United States
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Hinsdale, Illinois, 60521, United States
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Quincy, Illinois, 62305, United States
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Chicago, Illinois, 60637, United States
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Waterloo, Iowa, 50702, United States
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Lexington, Kentucky, 40509, United States
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Louisville, Kentucky, 40207, United States
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Shreveport, Louisiana, 71105, United States
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Shreveport, Louisiana, 71103, United States
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Baltimore, Maryland, 21202, United States
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Grand Rapids, Michigan, 49503, United States
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Rochester, Minnesota, 55905, United States
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Saint Paul, Minnesota, 55102, United States
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Bridgeton, Missouri, 63044, United States
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Lincoln, Nebraska, 68506, United States
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Camden, New Jersey, 08103, United States
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Buffalo, New York, 14221, United States
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Westbury, New York, 11590, United States
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Canton, Ohio, 44710, United States
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Medford, Oregon, 97504, United States
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Salem, Oregon, 97301, United States
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York, Pennsylvania, 17403, United States
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Pierre, South Dakota, 57501, United States
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Sioux Falls, South Dakota, 57105, United States
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Nashville, Tennessee, 37203, United States
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Chattanooga, Tennessee, 37404, United States
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Round Rock, Texas, 78665, United States
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Irving, Texas, 75063, United States
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Kingwood, Texas, 77339, United States
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Palestine, Texas, 75801, United States
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Fort Worth, Texas, 76104, United States
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Roanoke, Virginia, 24014, United States
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Norfolk, Virginia, 23502, United States
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Fairfax, Virginia, 22031, United States
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Spokane, Washington, 99208, United States
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Tacoma, Washington, 98405, United States
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Silverdale, Washington, 98383, United States
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Seattle, Washington, 98101, United States
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Vinh, 460000, Vietnam
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Hanoi, 100000, Vietnam
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Can Tho, 900000, Vietnam
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Status: Recruiting
Ho Chi Minh City, 700000, Vietnam
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Status: Recruiting
Jinan, 250117, China
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Status: Active, not recruiting
Changsha, 410013, China
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Status: Not yet recruiting
Shanghai, 200433, China
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Status: Not yet recruiting
München, 81925, Germany
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Status: Not yet recruiting
Budapest, 1083, Hungary
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Status: Not yet recruiting
Mumbai, 400012, India
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Status: Not yet recruiting
Kyoto, 612-8555, Japan
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Status: Not yet recruiting
Warsaw, 04-141, Poland
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Status: Not yet recruiting
Loma Linda, California, 92350, United States
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Status: Not yet recruiting
Ocala, Florida, 34474, United States
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Status: Not yet recruiting
Baton Rouge, Louisiana, 70808, United States
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Status: Not yet recruiting
South Portland, Maine, 04106, United States
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Status: Not yet recruiting
La Plata, 1900, Argentina
No email / No phone
Status: Withdrawn
Sint-Niklaas, 9100, Belgium
No email / No phone
Status: Withdrawn
São Paulo, 01246-000, Brazil
No email / No phone
Status: Withdrawn
Taubaté, 12030-200, Brazil
No email / No phone
Status: Withdrawn
Sydney, Nova Scotia, B1P 1P3, Canada
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Status: Withdrawn
Gyöngyös, 3200, Hungary
No email / No phone
Status: Withdrawn
Székesfehérvár, 8000, Hungary
No email / No phone
Status: Withdrawn
New Delhi, 110075, India
No email / No phone
Status: Withdrawn
Kolkata, 700054, India
No email / No phone
Status: Withdrawn
Groningen, 9713 GZ, Netherlands
No email / No phone
Status: Withdrawn
Lima, LIMA 29, Peru
No email / No phone
Status: Withdrawn
Lima, 15036, Peru
No email / No phone
Status: Withdrawn
Lima, Lima 34, Peru
No email / No phone
Status: Withdrawn
Lima, 15102, Peru
No email / No phone
Status: Withdrawn
Bialystok, 15-027, Poland
No email / No phone
Status: Withdrawn
Exeter, EX2 5DW, United Kingdom
No email / No phone
Status: Withdrawn
Chandler, Arizona, 85224, United States
No email / No phone
Status: Withdrawn
Gainesville, Florida, 32610, United States
No email / No phone
Status: Withdrawn
Atlanta, Georgia, 30342, United States
No email / No phone
Status: Withdrawn
Rockford, Illinois, 61114, United States
No email / No phone
Status: Withdrawn
Lexington, Kentucky, 40536, United States
No email / No phone
Status: Withdrawn
Alexandria, Louisiana, 71301, United States
No email / No phone
Status: Withdrawn
Duluth, Minnesota, 55805, United States
No email / No phone
Status: Withdrawn
Columbia, Missouri, 65212, United States
No email / No phone
Status: Withdrawn
Portland, Oregon, 97239, United States
No email / No phone
Status: Withdrawn
Pittsburgh, Pennsylvania, 15212, United States
No email / No phone
Status: Withdrawn
Providence, Rhode Island, 02903, United States
No email / No phone
Status: Withdrawn
Lubbock, Texas, 79410, United States
No email / No phone
Status: Withdrawn
Houston, Texas, 77090, United States
No email / No phone
Status: Withdrawn
Seattle, Washington, 98104, United States
No email / No phone
Status: Withdrawn
Wenatchee, Washington, 98801, United States
No email / No phone
Status: Withdrawn
La Crosse, Wisconsin, 54601, United States
No email / No phone
Status: Withdrawn
Bydgoszcz, 85-796, Poland
No email / No phone
Status: SUSPENDED
Biała Podlaska, 21-500, Poland
No email / No phone
Status: SUSPENDED
San Juan, 00918, Puerto Rico
No email / No phone
Status: SUSPENDED