Rilvegostomig + Bevacizumab for Liver Cancer

(ARTEMIDE-HCC01 Trial)

Recruiting at 85 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 is a Phase III, randomised, open-label, sponsor-blinded, 3-arm, multicentre, global study assessing the efficacy and safety of rilvegostomig in combination with bevacizumab with or without tremelimumab compared to atezolizumab in combination with bevacizumab. This study will be conducted in participants with advanced HCC who are not amenable to curative therapy or locoregional therapy

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 the combination of Rilvegostomig and Bevacizumab safe for humans?

Tremelimumab, which is similar to Rilvegostomig, has been studied for safety in various cancers. It can cause side effects like reduced appetite and diarrhea, and serious side effects occurred in about 32.6% of patients when combined with another drug. Safety in liver cancer specifically has been explored, but side effects can vary. ^{1 2 3 4 5}

What makes the drug combination of Rilvegostomig, Bevacizumab, and Tremelimumab unique for liver cancer?

This drug combination is unique because it combines Rilvegostomig and Bevacizumab, which target blood vessel growth in tumors, with Tremelimumab, an immunotherapy that helps the immune system attack cancer cells. This multi-faceted approach may offer a novel way to treat liver cancer by both cutting off the tumor's blood supply and enhancing the body's immune response. ^{2 4 5 6 7}

What data supports the effectiveness of the drug combination Rilvegostomig, Bevacizumab, and Tremelimumab 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 treatment called sorafenib. Additionally, Bevacizumab, when used with atezolizumab, is approved for first-line treatment of unresectable liver cancer, indicating its potential effectiveness in similar combinations. ^{2 4 7 8 9}

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

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]

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]

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]

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]

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]

Citations

1. United States 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. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Evidence to Date: Clinical Utility of Tremelimumab in the Treatment of Unresectable Hepatocellular Carcinoma. [2023]

3. England 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. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Dual Immunotherapy Makes Strides against HCC. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

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

6. Switzerland 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. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. [2022]

9. England 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. [2021]