Rilvegostomig + Bevacizumab for Liver Cancer

(ARTEMIDE-HCC01 Trial)

Recruiting at 181 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Immunosuppressants, Anticoagulants, others

Disqualifiers: Autoimmune disorders, Primary malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

1220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for advanced liver cancer that cannot be addressed with surgery or regional therapies. Researchers aim to evaluate the effectiveness of a drug combination, including rilvegostomig (an experimental treatment) and bevacizumab, against liver cancer compared to another existing drug combination. The trial includes different groups, with some participants receiving additional drugs like tremelimumab. Individuals who have not undergone previous systemic therapy for advanced liver cancer and whose condition precludes surgery might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use certain medications like high-dose aspirin, some blood thinners, or immunosuppressive treatments close to the start of the study. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining the drugs rilvegostomig and bevacizumab for liver cancer can lead to side effects such as loss of appetite and diarrhea. About 32.6% of patients experienced serious side effects when rilvegostomig was used with another drug. Tremelimumab, a drug similar to rilvegostomig, has also undergone safety testing in various cancer types and can cause similar side effects. These treatments are currently in advanced clinical trials, indicating they have passed earlier safety tests. It is crucial to consult your doctor to understand the risks and benefits for your specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about rilvegostomig because it offers a novel approach to treating liver cancer by potentially enhancing the immune system's ability to fight cancer cells. Unlike standard treatments like sorafenib and lenvatinib, which primarily target cancer cell growth, rilvegostomig is designed to stimulate a stronger immune response. When combined with bevacizumab, which inhibits blood vessel growth to tumors, and tremelimumab, which further boosts immune activity, this combination could provide a more comprehensive attack against liver cancer. This multi-faceted approach is what makes these treatments particularly promising.

What evidence suggests that this trial's treatments could be effective for liver cancer?

Research has shown that combining the drugs rilvegostomig and bevacizumab, which participants in this trial may receive in Arm B, might help treat advanced liver cancer. Previous studies found that this combination can help patients live longer and temporarily prevent their cancer from worsening. In Arm A of this trial, participants will receive rilvegostomig, bevacizumab, and an additional drug, tremelimumab. Adding tremelimumab has proven safe and shows a promising success rate, with 50% of patients responding well to the treatment. These findings suggest that these treatments could be a valuable option for people with liver cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer (HCC) who can't have surgery or local treatments. They should be in good physical condition, not previously treated with systemic therapy for HCC, and without certain other health issues like active infections or a history of other cancers.

Inclusion Criteria

At least one measurable target lesion

I am fully active or can carry out light work.

I do not have both HBV and HCV infections.

Exclusion Criteria

I haven't had radiotherapy (except for bone lesions) recently.

I have been treated with anti-CTLA-4 or anti-TIGIT before.

I have cancer that has spread to my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

A single-arm safety lead-in period to evaluate the safety and tolerability of rilvegostomig in combination with bevacizumab and tremelimumab

4-8 weeks

Randomised Treatment

Participants receive either rilvegostomig in combination with bevacizumab with or without tremelimumab, or atezolizumab in combination with bevacizumab

Up to approximately 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 6 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Rilvegostomig
• Tremelimumab

Trial Overview The study tests Rilvegostomig combined with Bevacizumab against Atezolizumab with Bevacizumab, and also explores adding Tremelimumab to the mix. It's a Phase III trial where patients are randomly assigned to one of three treatment groups.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 2 Interventions

Rilvegostomig, and bevacizumab

Group II: Arm A Experimental Treatment 3 Interventions

Tremelimumab , rilvegostomig and bevacizumab

Group III: Arm C Active Control 2 Interventions

Atezolizumab, and bevacizumab

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

Since the approval of sorafenib in 2007, multiple new treatments for unresectable hepatocellular carcinoma have emerged, including lenvatinib and the combination of atezolizumab plus bevacizumab, enhancing options for patients.

Recent studies presented at the 2022 ASCO Gastrointestinal Cancers Symposium indicate that the combination of durvalumab and tremelimumab may significantly improve overall survival compared to sorafenib, marking a potential shift in treatment strategies for both advanced and intermediate-stage hepatocellular carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New treatment paradigm with systemic therapy in intermediate-stage hepatocellular carcinoma. Kudo, M.[2023]

This phase Ib clinical trial is investigating the safety and efficacy of durvalumab, both alone and in combination with tremelimumab, alongside particle therapy for patients with advanced hepatocellular carcinoma (HCC) and macrovascular invasion, with a focus on monitoring adverse events and overall survival.

The trial will proceed to cohort B only if cohort A shows tolerable treatment outcomes, indicating a careful approach to ensure patient safety while exploring potentially synergistic effects of the therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab with or without tremelimumab combined with particle therapy for advanced hepatocellular carcinoma with macrovascular invasion: protocol for the DEPARTURE phase Ib trial. Ogasawara, S., Koroki, K., Makishima, H., et al.[2022]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

In the safety run-in of the IMMUNOBIL PRODIGE 57 trial involving 20 patients, the combination of durvalumab and tremelimumab with paclitaxel resulted in a high rate of dose-limiting toxicities (50%), including serious anaphylactic reactions and other severe adverse events.

Due to the safety concerns raised by the combination therapy, the trial will proceed with only the durvalumab and tremelimumab combination, indicating that the addition of paclitaxel may not be safe for patients with advanced biliary tract carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Boilève, A., Hilmi, M., Gougis, P., et al.[2021]

In a phase II trial involving 47 patients with treatment-refractory colorectal cancer, tremelimumab showed limited efficacy as a single agent, with only one patient (2%) achieving a partial response and 21 patients (45%) surviving for at least 180 days after treatment.

The treatment was associated with some grade 3/4 adverse events, including diarrhea and ulcerative colitis, but these were generally manageable, suggesting that while tremelimumab may not be effective alone, it could be safe for further exploration in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. Chung, KY., Gore, I., Fong, L., et al.[2022]

In the phase III HIMALAYA trial, patients with inoperable hepatocellular carcinoma who received a single dose of tremelimumab combined with monthly durvalumab showed improved overall survival compared to those treated with sorafenib.

This suggests that the combination therapy may be a more effective first-line treatment option for this type of liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual Immunotherapy Makes Strides against HCC. [2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06921785

NCT06921785 | Phase III Study of Rilvegostomig in ... The purpose of this study is to assess the efficacy and tolerability of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12228486/

Retrospective Multicentre Real-Life Study Evaluating the ... The ImBrave 150 trial successfully demonstrated that overall survival (OS) and progression-free survival (PFS) was improved among patients ...

3. clinicaltrials.eu clinicaltrials.eu/trial/study-of-rilvegostomig-with-bevacizumab-and-tremelimumab-as-first-line-treatment-for-patients-with-advanced-liver-cancer/

Study of Rilvegostomig with Bevacizumab and ... The main purpose of this research is to determine if combining rilvegostomig with tremelimumab and bevacizumab is more effective than using ...

4. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7029C00001

Phase III Study of Rilvegostomig in Combination with ... The purpose of this study is to assess the efficacy and tolerability of rilvegostomig in combination with bevacizumab with or without tremelimumab as first-line ...

5. withpower.com withpower.com/trial/phase-3-carcinoma-4-2025-98645

Rilvegostomig + Bevacizumab for Liver Cancer Tremelimumab, when combined with another drug called durvalumab, has shown to improve survival in patients with advanced liver cancer compared to another ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2025-05155

Phase III Study of Rilvegostomig in Combination With ... This is a Phase III, randomised, open-label, sponsor-blinded, 3-arm, multicentre, global study assessing the efficacy and safety of rilvegostomig in ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT444186

GEMINI-Hepatobiliary: A phase 2 study of novel first-line ... A phase 2, open-label, multidrug, multicenter, master protocol study designed to evaluate the preliminary efficacy and safety of novel IO bispecific mAbs.