Trial: Phase III Study of Rilvegostomig in Com…

Trial Details

Sponsor: AstraZeneca (industry)

Phase: 3

Start date: May 6, 2025

Planned enrollment: 1220

Trial ID: NCT06921785

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: Rilvegostomig (AZD2936)

HealthScout AI Analysis

Goal: Evaluate whether adding the PD-1/TIGIT bispecific antibody rilvegostomig to bevacizumab, with or without a single‑agent CTLA‑4 antibody (tremelimumab), improves outcomes versus the standard first‑line regimen of atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (HCC) not amenable to curative or locoregional therapy.

Patients: Adults with unresectable, locally advanced, metastatic, or otherwise non–locoregionally treatable HCC; BCLC stage B not eligible for LRT or stage C; Child-Pugh class A; ECOG 0–1; at least one measurable lesion. No prior systemic therapy for intermediate/advanced disease. Key exclusions include active autoimmune disease requiring immunosuppression, significant bleeding risk or need for therapeutic anticoagulation/antiplatelet agents, clinically meaningful effusions, hepatic encephalopathy, CNS metastases, fibrolamellar/sarcomatoid/mixed histologies, active infections or immunodeficiency, and prior anti-CTLA-4 or anti-TIGIT exposure.

Design: Phase III, global, multicentre, randomized, open-label, sponsor-blinded, three-arm study with an initial safety lead-in of the triplet (rilvegostomig + bevacizumab + tremelimumab) followed by a randomized period. Planned enrollment ~1220 participants.

Treatments: Arm A: Tremelimumab + rilvegostomig + bevacizumab. Arm B: Rilvegostomig + bevacizumab. Arm C (control): Atezolizumab + bevacizumab, a standard first-line regimen in advanced HCC that improves OS versus sorafenib. Rilvegostomig (AZD2936) is a humanized IgG1 bispecific antibody targeting PD‑1 and TIGIT to enhance anti-tumor T-cell activity; Fc modifications reduce effector functions. Early-phase data in heavily pretreated NSCLC showed acceptable tolerability with mostly grade 1–3 immune-related AEs, a recommended dose of 750 mg IV q3w, approximately 90% receptor occupancy at adequate doses, and signals of antitumor activity (confirmed partial responses in a subset and disease control in about one-third). Tremelimumab is a CTLA‑4 antibody; bevacizumab is an anti‑VEGF monoclonal antibody; atezolizumab is an anti‑PD‑L1 antibody.

Outcomes: Primary: Overall survival (OS) for Arm A versus Arm C. Key secondary: OS for Arm B versus Arm C; PFS and ORR per RECIST 1.1 for Arms A and B versus Arm C; OS, PFS, ORR, and DoR for Arm A versus Arm B; association of PD‑L1 expression with OS, PFS, ORR, and DoR for comparisons versus control; safety (AEs/SAEs graded by CTCAE v5.0); immunogenicity (anti-drug antibodies to tremelimumab and rilvegostomig). Time frame up to approximately 6 years.

Burden on patient: Moderate. As a Phase III immunotherapy/anti‑VEGF study, patients will undergo regular IV infusions, periodic imaging (e.g., every 6–8–12 weeks consistent with RECIST assessments), routine labs, and safety monitoring similar to standard-of-care checkpoint/anti‑VEGF regimens. The safety lead-in triplet may entail closer early monitoring. Additional procedures include biomarker sampling (including PD‑L1 testing) and immunogenicity assessments; no intensive pharmacokinetic schedules are specified. Travel and infusion time commitments are comparable to other first‑line IV regimens in advanced HCC, with added visits for long-term follow-up up to 6 years.

Eligibility

Show Criteria

Inclusion Criteria:

* Locally advanced or metastatic and/or unresectable HCC

* WHO/ECOG performance status of 0 or 1

* BCLC stage B (that is not eligible for locoregional therapy) or stage C. Child-Pugh Score class A

* At least one measurable target lesion

* co-infected with HBV and HCV are not eligible

* Adequate organ and bone marrow function measured during the screening period

* Must not have received prior systemic therapy for intermediate, advanced, or metastatic HCC.

* Disease that is not amenable to curative surgical and/or locoregional therapies. For participants who received locoregional therapy for HCC, locoregional therapy must have been completed ≥ 28 days prior to the baseline scan for the current study.

Exclusion Criteria:

Medical condition

* Any evidence of uncontrolled intercurrent diseases

* Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment

* History of another primary malignancy

* Persistent toxicities caused by previous anti-cancer therapy excluding alopecia, not yet improved to Grade ≤ 1 or baseline.

* Clinically meaningful ascites, pleural effusion, or pericardial effusion requiring non-pharmacologic intervention to maintain symptomatic control within 6 months prior to the first scheduled dose.

* History of active primary immunodeficiency or active infection

* History of hepatic encephalopathy

* Current or recent (within 10 days of first dose of study treatment) use of aspirin (≥ 325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and cilostazol

* Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purposes is ineligible

Bleeding or other risks

HCC related

* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.

* Central nervous system metastases or spinal cord compression (including asymptomatic and adequately treated disease)

* Prior treatment with anti-CTLA-4 and/or anti-TIGIT.

* Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment

Sites (127)

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Santa Maria, 97015-450, Brazil

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São Paulo, 04014-002, Brazil

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São Paulo, 05652-9000, Brazil

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Vitória, 29043-272, Brazil

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Porto Alegre, 91350-200, Brazil

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Edmonton, Alberta, T6G 1Z2, Canada

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Halifax, Nova Scotia, B3H 1V7, Canada

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Barrie, Ontario, L4M 6M2, Canada

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Cambridge, Ontario, N1R 3G2, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Toronto, Ontario, M5G 1X6, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Montreal, Quebec, H2X 0A9, Canada

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Québec, Quebec, G1J 4Z1, Canada

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Lishui, 323000, China

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Wenzhou, 325000, China

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Shanghai, 201114, China

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Nanchang, 330029, China

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Nanchang, 330008, China

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Beijing, CN-100730, China

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Changchun, 130021, China

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Chengdu, 610041, China

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Deyang, 618000, China

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Guangzhou, 510515, China

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Luoyang, 471000, China

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Rennes, 35000, France

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Toulouse, 31059, France

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Clichy, 92118, France

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Lille, 59000, France

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Lyon, 69317, France

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Nantes, 44093, France

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Nice, 06200, France

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Pessac, 33604, France

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Bonn, 53127, Germany

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Aachen, 52074, Germany

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Berlin, 13353, Germany

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Dortmund, 44137, Germany

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Dresden, 01307, Germany

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Essen, 45122, Germany

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Frankfurt, 60488, Germany

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Frankfurt, 60590, Germany

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Göttingen, 37075, Germany

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Hamburg, 20246, Germany

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Hanover, 30623, Germany

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Leipzig, 4103, Germany

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Lübeck, 23538, Germany

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Magdeburg, 39120, Germany

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Moers, 47441, Germany

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München, 81377, Germany

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Regensburg, 93053, Germany

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Ulm, 89081, Germany

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Shatin, 00000, Hong Kong

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Hong Kong, 999077, Hong Kong

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Mumbai, 400012, India

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Nashik, 422011, India

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Delhi, 110029, India

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Hyderabad, 500032, India

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Vadodara, 391760, India

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Ahmedabad, 380058, India

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Bangalore, 560027, India

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Binnāguri, 734015, India

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Dehradun, 248016, India

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Bologna, 40138, Italy

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Rozzano, 20089, Italy

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Roma, 00168, Italy

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Pisa, 56126, Italy

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Perugia, 06132, Italy

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Palermo, 90127, Italy

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Milan, 20162, Italy

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Milan, 20132, Italy

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Sendai, 981-0914, Japan

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Tokyo, 104-0045, Japan

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Yokohama, 232-0024, Japan

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Yokohama, 241-8515, Japan

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Kurume-shi, 830-0011, Japan

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Kyoto, 602-8566, Japan

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Mitaka-shi, 181-8611, Japan

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Morioka, 028-3695, Japan

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Musashino-shi, 180-8610, Japan

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Okayama, 700-8558, Japan

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Osaka, 541-8567, Japan

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Osakasayama-shi, 589-8511, Japan

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Suita-shi, 565-0871, Japan

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Chiba, 260-8677, Japan

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Hiroshima, 734-8530, Japan

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Hiroshima, 734-8551, Japan

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Kashiwa, 227-8577, Japan

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Kita-gun, 761-0793, 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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Madrid, 28007, Spain

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Madrid, 28027, Spain

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Madrid, 28040, Spain

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Santander, 39008, Spain

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Barcelona, 08036, Spain

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Barcelona, 08035, Spain

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Taoyuan District, 333, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 112, Taiwan

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Bangkok, 10210, Thailand

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Chiang Mai, 50200, Thailand

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Dusit, 10300, Thailand

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Hat Yai, 90110, Thailand

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Muang, 40002, Thailand

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Ubonratchathani, 34000, Thailand

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Bangkok, 10700, Thailand

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Erzurum, 25240, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Istanbul, 34180, Turkey (Türkiye)

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Altındağ, 06230, Turkey (Türkiye)

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Ankara, 06530, Turkey (Türkiye)

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Phoenix, Arizona, 85054, United States

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Palo Alto, California, 94304, United States

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New Haven, Connecticut, 06511, United States

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Jacksonville, Florida, 32224, United States

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Atlanta, Georgia, 30322, 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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New Brunswick, New Jersey, 08901, United States

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New York, New York, 10065, United States

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New York, New York, 10029, United States

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Oklahoma City, Oklahoma, 73104, United States

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Arlington, Virginia, 22201, United States

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Milwaukee, Wisconsin, 53226, United States

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Ho Chi Minh City, 700000, Vietnam

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Hanoi, 100000, Vietnam

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A Phase III, Randomised, Open-label, Sponsor-blinded, Multicentre Study of Rilvegostomig in Combination With Bevacizumab With or Without Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: Rilvegostomig (AZD2936)

Overview

Mechanism of Action

Efficacy

Safety

Further Reading

HealthScout AI Analysis

Eligibility

Show Criteria

Sites (127)

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