Sponsor: AstraZeneca (industry)
Phase: 3
Start date: March 27, 2025
Planned enrollment: 600
Rilvegostomig, also known as AZD2936, is an investigational bispecific antibody developed by AstraZeneca. It targets both PD-1 and TIGIT receptors and is being evaluated for the treatment of advanced or metastatic PD-L1–positive non–small cell lung cancer (NSCLC) in patients who have progressed on prior checkpoint inhibitors. (targetedonc.com)
Rilvegostomig is designed to simultaneously inhibit PD-1 and TIGIT pathways, both of which are involved in immune suppression within the tumor microenvironment. By blocking these receptors, rilvegostomig aims to enhance T-cell activity and counteract tumor-induced immunosuppression. (targetedonc.com)
In the phase 1/2 ARTEMIDE-01 trial, rilvegostomig demonstrated preliminary signs of efficacy:
Rilvegostomig was generally well tolerated:
Last updated: Apr 2025
Goal: To determine whether first-line trastuzumab deruxtecan (T-DXd) combined with rilvegostomig or with pembrolizumab improves progression-free survival versus standard carboplatin/paclitaxel plus pembrolizumab in patients with HER2-expressing, pMMR primary advanced or recurrent endometrial cancer.
Patients: Adults with histologically confirmed epithelial endometrial carcinoma (all histologies except sarcomas; carcinosarcomas allowed) that is HER2 IHC 3+ or 2+ and mismatch repair proficient by central testing. Eligible disease settings include primary Stage III with measurable disease, primary Stage IV regardless of measurability, or first recurrence regardless of measurability. Patients must be systemic therapy–naïve in the advanced/recurrent setting; prior adjuvant/neoadjuvant chemotherapy is allowed if relapse occurred ≥6 months after completion. ECOG 0–1, adequate organ function, LVEF ≥50%, and provision of adequate non-irradiated FFPE tissue for central HER2/MMR/PD-L1 testing are required. Key exclusions include prior ADCs or immune checkpoint inhibitors, significant cardiac disease, history or suspicion of ILD/pneumonitis, clinically significant pulmonary comorbidity, uncontrolled autoimmune disease, uncontrolled infections including active TB or hepatitis, and uncontrolled CNS disease.
Design: Multicenter, open-label, sponsor-blinded, randomized, controlled Phase III trial. Approximately 600 participants randomized to one of three arms; efficacy assessed by blinded independent central review for the primary endpoint. First-line treatment setting with stratification by biomarker-defined subgroups through central testing.
Treatments: Arm A: T-DXd IV every 3 weeks plus rilvegostomig IV every 3 weeks until progression or discontinuation. Arm B: T-DXd IV every 3 weeks plus pembrolizumab IV every 3 weeks until progression or discontinuation. Arm C (control): Carboplatin plus paclitaxel and pembrolizumab every 3 weeks for 6 cycles, then pembrolizumab maintenance every 6 weeks to complete up to 20 cycles total; at investigator discretion, combination may continue up to 10 cycles; docetaxel may replace paclitaxel after hypersensitivity. Trastuzumab deruxtecan is an anti-HER2 antibody–drug conjugate delivering a topoisomerase I inhibitor (DXd) with bystander effect; it has demonstrated substantial antitumor activity across HER2-expressing tumors and is associated with risks including interstitial lung disease/pneumonitis and cytopenias. Rilvegostomig is an investigational bispecific IgG1 antibody targeting PD-1 and TIGIT with Fc-silencing mutations to limit effector functions; in a Phase I NSCLC study it showed acceptable tolerability, dose-proportional exposure, approximately 90% dual receptor occupancy at ≥210 mg, and preliminary antitumor activity in heavily pretreated patients, supporting Phase III evaluation. Pembrolizumab plus carboplatin/paclitaxel represents an established first-line chemoimmunotherapy backbone in endometrial cancer.
Outcomes: Primary: Progression-free survival by blinded independent central review per RECIST 1.1. Key secondary endpoints include overall survival; investigator-assessed PFS; PFS2; objective response rate and duration of response by BICR and investigator; safety and tolerability (AEs, SAEs, AESIs, labs, vitals, ECG, echocardiography/MUGA); pharmacokinetics of T-DXd, total anti-HER2 antibody, DXd, and rilvegostomig; immunogenicity (ADAs); patient-reported tolerability (symptomatic AEs and overall side-effect bother); and exploratory assessment of PFS and OS by MMR status and by HER2 expression to evaluate diagnostic utility. Follow-up for PFS up to approximately 45 months and for OS up to approximately 70 months.
Burden on patient: Moderate. Requirements include central confirmation of HER2 and MMR status on adequate FFPE tissue, which may necessitate a diagnostic or archival sample meeting quality criteria. Treatment visits are every 3 weeks for combination therapy and involve IV infusions, routine labs, vitals, ECGs, and echocardiography/MUGA to monitor LVEF, plus periodic imaging per RECIST; the control arm includes multi-drug chemotherapy for 6–10 cycles with associated clinic time and infusion-related logistics. Experimental arms include pharmacokinetic and immunogenicity blood draws at predefined time points, adding to visit duration. Safety monitoring for T-DXd includes vigilance for ILD/pneumonitis with potential additional imaging or pulmonology evaluation if symptomatic. Overall visit frequency and imaging schedule are similar to standard-of-care chemoimmunotherapy, but added PK/ADA sampling and cardiac monitoring increase time and procedural burden compared with routine care.
* Key Inclusion Criteria:
* Participants must be ≥ 18 years of age at the time of screening. Other age restrictions may apply as per local regulations.
* Histologically confirmed diagnosis of epithelial endometrial carcinoma. All histologies are allowed except for sarcomas (carcinosarcomas are allowed).
* Following surgery or diagnostic biopsy, participant must have primary advanced disease (Stage III/IV) or first recurrent endometrial cancer and meet at least one of the following criteria:
* Primary Stage III (per FIGO 2023) disease with measurable disease at baseline per RECIST 1.1 based on the investigator's assessment.
* Primary Stage IV disease (per FIGO 2023) regardless of presence of measurable disease at baseline.
* First recurrent disease regardless of presence of measurable disease at baseline.
* Endometrial cancer with HER2 IHC expression of 3+ or 2+ as assessed by prospective central testing.
* Endometrial cancer that is determined pMMR by prospective central IHC testing.
* Provision of adequate FFPE tumor tissue sample of a tumor lesion that was not previously irradiated for central HER2, MMR, and PD-L1 IHC testing and valid central test results for randomization/ stratification.
* Prior therapy:
* Naïve to first-line systemic anticancer therapy. Participants may have received one prior line of adjuvant/neoadjuvant chemotherapy with curative intent (chemotherapy or chemoradiation) if disease recurrence or progression occurred ≥ 6 months after last dose of chemotherapy. Prior trastuzumab in the adjuvant/neoadjuvant setting is allowed.
* No prior exposure to ADCs or immune checkpoint inhibitors including (but not limited to) anti-PD-1/PD-L1/PD-L2 and anti-CTLA-4 antibodies and therapeutic anticancer vaccines.
* Participants may have received prior radiation therapy for the treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy. Adequate treatment washout period is required.
* Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
* Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.
* Adequate organ and bone marrow function within 14 days before randomization.
* Key Exclusion Criteria:
* History of organ transplant
* Uncontrolled intercurrent illness, including, but not limited to ongoing or active known infection, serious chronic gastrointestinal conditions associated with diarrhea and active non-infectious skin disease requiring systemic treatment.
* Spinal cord compression or clinically active central nervous system metastases
* Participants with a medical history of myocardial infarction (MI) within 6 months before randomization, or symptomatic congestive heart failure (CHF) (NYHA Class II to IV), clinically significant arrhythmia, or cardiomyopathy of any etiology. Participants with troponin levels above ULN at screening (as defined by the manufacturer), should have a cardiologic consultation before enrollment to rule out MI
* History of (non-infectious) ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
* Lung criteria:
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within 3 months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion etc.).
* Any autoimmune, connective tissue or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of screening.
* Prior pneumonectomy (complete).
* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
* Active primary immunodeficiency/ active infectious disease(s) including:
* Tuberculosis (TB)
* HIV infection that is not well controlled.
* Chronic or active hepatitis B, chronic or active hepatitis C; however, participants who have chronic hepatitis B and are receiving suppressive antiviral therapy are allowed to be enrolled if alanine aminotransferase (ALT) is normal and viral load is controlled.
* Any concurrent anticancer treatment without an adequate washout period prior to the first dose of study intervention. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., HRT) is allowed.
East Melbourne, 3002, Australia
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Nedlands, 6009, Australia
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South Brisbane, 4101, Australia
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Blacktown, 2148, Australia
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Wein, 1130, Austria
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Vienna, 1090, Austria
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Linz, 4021, Austria
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Innsbruck, 6020, Austria
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Brussels, 1200, Belgium
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Liège, 4000, Belgium
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Anderlecht, 1070, Belgium
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Leuven, 3000, Belgium
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Ghent, 9000, Belgium
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Charleroi, 6060, Belgium
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Status: Withdrawn
Teresina, 64049-200, Brazil
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São Paulo, 1409, Brazil
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São Paulo, 01317-001, Brazil
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São Paulo, 01246-000, Brazil
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Barretos, 14784-057, Brazil
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Belo Horizonte, 30130 100, Brazil
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Goiânia, 74000-000, Brazil
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Londrina, 86015-520, Brazil
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Porto Alegre, 90020-090, Brazil
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Porto Alegre, 90610000, Brazil
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Rio de Janeiro, 20220-410, Brazil
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Salvador, 41.950-610, Brazil
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Calgary, Alberta, T2N 5G2, Canada
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Edmonton, Alberta, T6G 1Z2, Canada
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Winnipeg, Manitoba, R3E 0V9, Canada
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Status: Not yet recruiting
Halifax, Nova Scotia, B3H 2Y9, Canada
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Status: Withdrawn
London, Ontario, N6A 4L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Status: Recruiting
Montreal, Quebec, H3G 1A4, Canada
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Québec, Quebec, G1J 4Z1, Canada
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Status: Recruiting
Montreal, Quebec, H2X 0A9, Canada
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Status: Recruiting
Montreal, Quebec, H1T 2M4, Canada
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Status: Not yet recruiting
Chengdu, 610041, China
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Yibin, 610500, China
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Xuzhou, 221009, China
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Xi'an, 710061, China
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Wuhan, 430022, China
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Wuhan, 430000, China
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Status: Recruiting
Ürümqi, 830000, China
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Status: Withdrawn
Tianjin, 300060, China
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Status: Recruiting
Taiyuan, 030001, China
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Shenyang, 110042, China
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Shenyang, 110004, China
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Shantou, China
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Status: Recruiting
Shanghai, 201318, China
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Shanghai, 200011, China
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Status: Recruiting
Nanning, 530021, China
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Status: Recruiting
Nanchang, 330006, China
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Status: Recruiting
Lanzhou, 730030, China
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Status: Recruiting
Kunming, 650118, China
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Jining, 272029, China
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Jinan, 250117, China
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Status: Recruiting
Jinan, 250021, China
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Status: Recruiting
Hefei, 230001, China
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Status: Not yet recruiting
Harbin, 150049, China
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Hangzhou, 310022, China
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Haikou, 570311, China
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Status: Recruiting
Guangzhou, 510120, China
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Status: Recruiting
Guangzhou, 510080, China
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Guangzhou, 510060, China
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Status: Recruiting
Fuzhou, 350014, China
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Fuzhou, 350001, China
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Status: Recruiting
Chongqing, 400030, China
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Chengdu, 610072, China
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Status: Recruiting
Changsha, 410013, China
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Status: Recruiting
Changchun, 130021, China
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Status: Not yet recruiting
Beijing, 100142, China
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Status: Recruiting
Aalborg, 9100, Denmark
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Status: Not yet recruiting
Herlev, 2730, Denmark
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Status: Withdrawn
København Ø, 2100, Denmark
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Status: Not yet recruiting
Odense, 5000, Denmark
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Status: Not yet recruiting
Helsinki, 00290, Finland
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Oulu, 90029, Finland
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Tampere, 33520, Finland
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Turku, 20520, Finland
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Status: Not yet recruiting
Paris, 75015, France
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Besançon, 25030, France
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Bordeaux, 33076, France
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Caen, 14076, France
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Status: Not yet recruiting
Clermont-Ferrand, 63000, France
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Status: Not yet recruiting
Lyon, 69373, France
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Montpellier, 34298, France
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Nice, 06100, France
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Plérin, 22190, France
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Status: Not yet recruiting
Poitiers, 86021, France
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Status: Not yet recruiting
Saint-Herblain, 44805, France
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Status: Not yet recruiting
Toulouse, 31059, France
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Status: Not yet recruiting
Leipzig, 04103, Germany
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Status: Not yet recruiting
Marburg, 35043, Germany
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Münster, 48149, Germany
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Status: Not yet recruiting
Dresden, 01307, Germany
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Status: Not yet recruiting
Saarbrücken, 66113, Germany
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Status: Not yet recruiting
Dessau, 06847, Germany
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Status: Not yet recruiting
Chemnitz, 09116, Germany
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Status: Not yet recruiting
Berlin, 13353, Germany
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Status: Not yet recruiting
Hamburg, 20246, Germany
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Kassel, 34125, Germany
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Status: Not yet recruiting
Mannheim, 68167, Germany
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Status: Not yet recruiting
Essen, 45147, Germany
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Status: Not yet recruiting
Debrecen, 4032, Hungary
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Status: Not yet recruiting
Budapest, 1122, Hungary
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Budapest, 1088, Hungary
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Status: Not yet recruiting
Monza, 20900, Italy
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Status: Not yet recruiting
Milan, 20159, Italy
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Milan, 20141, Italy
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Status: Not yet recruiting
Florence, 50134, Italy
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Status: Not yet recruiting
Catania, 95100, Italy
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Status: Not yet recruiting
Turin, 10128, Italy
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Status: Not yet recruiting
Torino, 10128, Italy
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Status: Not yet recruiting
Rome, 00168, Italy
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Roma, 00144, Italy
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Status: Not yet recruiting
Reggio Emilia, 422122, Italy
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Status: Not yet recruiting
Napoli, 80131, Italy
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Status: Not yet recruiting
Milan, 20162, Italy
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Status: Not yet recruiting
Sendai, 980-8574, Japan
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Status: Not yet recruiting
Hidaka-shi, 350-1298, Japan
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Status: Not yet recruiting
Isehara-shi, 259-1193, Japan
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Status: Not yet recruiting
Kashiwa, 227-8577, Japan
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Status: Not yet recruiting
Kashiwa-shi, 277-8567, Japan
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Status: Not yet recruiting
Kobe, 650-0047, Japan
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Status: Not yet recruiting
Kōtoku, 135-8550, Japan
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Status: Not yet recruiting
Kurume-shi, 830-0011, Japan
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Status: Recruiting
Matsuyama, 791-0280, Japan
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Status: Not yet recruiting
Morioka, 028-3695, Japan
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Status: Recruiting
Nagoya, 464-8681, Japan
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Status: Not yet recruiting
Nakagami-gun, 903-0215, Japan
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Status: Recruiting
Niigata, 951-8520, Japan
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Status: Recruiting
Osaka, 541-8567, Japan
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Status: Not yet recruiting
Ota-shi, 373-8550, Japan
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Status: Not yet recruiting
Sapporo, 060-8648, Japan
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Status: Not yet recruiting
Akashi-shi, 673-8558, Japan
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Status: Not yet recruiting
Shinjuku-ku, 160-8582, Japan
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Status: Not yet recruiting
Sunto-gun, 411-8777, Japan
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Status: Not yet recruiting
Tokyo, 104-0045, Japan
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Status: Recruiting
Amsterdam, 1066CX, Netherlands
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Status: Not yet recruiting
Leiden, 2333 ZA, Netherlands
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Status: Not yet recruiting
Nijmegen, 6525 GA, Netherlands
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Status: Not yet recruiting
Rotterdam, 3015 GD, Netherlands
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Status: Not yet recruiting
Stavanger, 4011, Norway
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Status: Not yet recruiting
Oslo, 0379, Norway
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Status: Not yet recruiting
Lodz, 93-338, Poland
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Status: Not yet recruiting
Szczecin, 70-111, Poland
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Status: Not yet recruiting
Siedlce, 08-110, Poland
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Status: Not yet recruiting
Poznan, 60-569, Poland
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Status: Not yet recruiting
Gdansk, 80-214, Poland
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Status: Not yet recruiting
Bialystok, 15-027, Poland
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Status: Not yet recruiting
Suwon, 16499, South Korea
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Status: Recruiting
Goyang-si, 10408, South Korea
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Status: Recruiting
Seoul, 03080, South Korea
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Status: Recruiting
Seoul, 03722, South Korea
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Status: Recruiting
Seoul, 05505, South Korea
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Status: Recruiting
Seoul, 06351, South Korea
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Status: Recruiting
Córdoba, 14004, Spain
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Status: Not yet recruiting
A Coruña, 15009, Spain
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Status: Not yet recruiting
Donostia / San Sebastian, 20014, Spain
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Status: Not yet recruiting
El Palmar, 30120, Spain
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Status: Not yet recruiting
L'Hospitalet de Llobregat, 08908, Spain
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Status: Not yet recruiting
Madrid, 28034, Spain
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Madrid, 28041, Spain
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Status: Not yet recruiting
Palma de Mallorca, 07010, Spain
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Status: Not yet recruiting
Valencia, 46006, Spain
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Status: Not yet recruiting
Valencia, 46009, Spain
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Zaragoza, 50009, Spain
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Status: Not yet recruiting
Uppsala, 751 85, Sweden
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Status: Not yet recruiting
Stockholm, 17164, Sweden
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Lund, 22185, Sweden
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Status: Not yet recruiting
Linköping, 581 85, Sweden
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Status: Not yet recruiting
Zurich, 8091, Switzerland
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Status: Not yet recruiting
Liestal, CH- 4410, Switzerland
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Status: Not yet recruiting
Frauenfeld, 8501, Switzerland
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Status: Withdrawn
Tainan City, 704, Taiwan
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Status: Recruiting
Kaohsiung City, 81362, Taiwan
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Status: Recruiting
Changhua, 500, Taiwan
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Status: Recruiting
New Taipei City, 220, Taiwan
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Status: Recruiting
Taipei, 10449, Taiwan
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Status: Recruiting
Taichung, 40705, Taiwan
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Status: Recruiting
Taunton, TA1 5DA, United Kingdom
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Status: Not yet recruiting
Bath, BA1 3NG, United Kingdom
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Status: Not yet recruiting
Cambridge, CB2 0QQ, United Kingdom
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Status: Not yet recruiting
Leeds, LS9 7TF, United Kingdom
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Status: Not yet recruiting
London, EC1A 7BE, United Kingdom
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Status: Not yet recruiting
Manchester, M20 4BX, United Kingdom
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Status: Not yet recruiting
Northwood, HA6 2RN, United Kingdom
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Status: Not yet recruiting
Tucson, Arizona, 85704, United States
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Status: Withdrawn
Little Rock, Arkansas, 72205, United States
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Status: Not yet recruiting
La Jolla, California, 92037, United States
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Status: Not yet recruiting
Sylmar, California, 91342, United States
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Status: Withdrawn
Palo Alto, California, 94304, United States
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Status: Withdrawn
Fort Myers, Florida, 33908, United States
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Status: Not yet recruiting
West Palm Beach, Florida, 33401, United States
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Status: Not yet recruiting
Tampa, Florida, 33612, United States
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Status: Not yet recruiting
St. Petersburg, Florida, 33705, United States
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Status: Not yet recruiting
Miami Beach, Florida, 33140, United States
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Status: Not yet recruiting
Augusta, Georgia, 30912, United States
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Status: Not yet recruiting
Honolulu, Hawaii, 96813, United States
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Status: Withdrawn
Niles, Illinois, 60714, United States
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Status: Not yet recruiting
Evanston, Illinois, 60201, United States
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Status: Not yet recruiting
Shreveport, Louisiana, 71103, United States
No email / No phone
Status: Recruiting
Baltimore, Maryland, 21201, United States
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Status: Not yet recruiting
Worcester, Massachusetts, 01655, United States
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Status: Not yet recruiting
Boston, Massachusetts, 02111, United States
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Status: Not yet recruiting
Detroit, Michigan, 48201, United States
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Status: Not yet recruiting
Ann Arbor, Michigan, 48109, United States
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Status: Not yet recruiting
Minneapolis, Minnesota, 55455, United States
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Status: Not yet recruiting
Rochester, Minnesota, 55905, United States
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Status: Not yet recruiting
Jackson, Mississippi, 39216, United States
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Status: Not yet recruiting
St Louis, Missouri, 63141, United States
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Status: Not yet recruiting
Las Vegas, Nevada, 89169, United States
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Status: Withdrawn
Hackensack, New Jersey, 07601, United States
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Status: Not yet recruiting
Albuquerque, New Mexico, 87109, United States
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Status: Not yet recruiting
New York, New York, 10075, United States
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Status: Withdrawn
New York, New York, 10065, United States
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Status: Not yet recruiting
New York, New York, 10016, United States
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Status: Withdrawn
Winston-Salem, North Carolina, 27103, United States
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Status: Not yet recruiting
Charlotte, North Carolina, 28204, United States
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Status: Not yet recruiting
Cincinnati, Ohio, 45220, United States
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Status: Not yet recruiting
Tulsa, Oklahoma, 74134, United States
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Status: Withdrawn
Eugene, Oregon, 97401, United States
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Status: Not yet recruiting
Philadelphia, Pennsylvania, 19111, United States
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Status: Not yet recruiting
Pittsburgh, Pennsylvania, 15224, United States
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Status: Not yet recruiting
Abington, Pennsylvania, 19001, United States
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Status: Withdrawn
Hershey, Pennsylvania, 17033, United States
No email / No phone
Status: Withdrawn
Providence, Rhode Island, 02905, United States
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Status: Not yet recruiting
Charleston, South Carolina, 29425, 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
Irving, Texas, 75063, United States
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Status: Not yet recruiting
Fredericksburg, Texas, 78624, United States
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Status: Not yet recruiting
Austin, Texas, 78758, United States
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Status: Not yet recruiting
Houston, Texas, 77030, United States
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Status: Not yet recruiting
Saint Johnsbury, Vermont, 05819, United States
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Status: Not yet recruiting
Charlottesville, Virginia, 22908, United States
No email / No phone
Status: Not yet recruiting
Seattle, Washington, 98133, United States
No email / No phone
Status: Withdrawn
Madison, Wisconsin, 53705, United States
No email / No phone
Status: Not yet recruiting