BC3402 + Tremelimumab + Durvalumab for Liver Cancer

Overseen By Wen Wee Ma, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Case Comprehensive Cancer Center

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-PD-L1, Anti-CTLA-4

Disqualifiers: Organ transplant, Hypertension, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new experimental treatment called BC3402 for liver cancer. Participants will receive BC3402 along with two immunotherapy drugs, Durvalumab and Tremelimumab, to evaluate the combination's effectiveness against the disease. Candidates include those with liver cancer that cannot be surgically removed and who have not received prior systemic treatments (whole-body treatments). The trial aims to determine if this new approach can benefit individuals with advanced liver cancer. As a Phase 1, Phase 2 trial, the research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants the opportunity to be among the first to potentially benefit from this innovative approach.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take any other cancer treatments while participating, and if you have Hepatitis B, you must continue antiviral therapy during the study and for 6 months after.

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

Research has shown that the combination of Tremelimumab and Durvalumab has been tested for safety in various cancers, including liver cancer. Common side effects include rash and tiredness. Initial findings indicate a 19.1% chance of serious side effects, but few people stop treatment or experience severe problems due to these side effects. This suggests that the treatment is generally manageable.

Tremelimumab and Durvalumab are already used together for some conditions, providing some understanding of their safety. However, BC3402 remains experimental and lacks FDA approval, so its safety is less known. The trial under consideration is in the early stages (Phase 1/2), focusing on safety and determining the best dose. While safety data is limited, the trial is designed to closely monitor for any new side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BC3402 combined with Tremelimumab and Durvalumab for liver cancer because it offers a novel approach compared to existing treatments like sorafenib or lenvatinib. This combination therapy is unique because BC3402 is designed to work synergistically with immune checkpoint inhibitors Tremelimumab and Durvalumab, potentially enhancing the immune system's ability to target and destroy cancer cells. Unlike traditional treatments that mainly inhibit tumor growth, this regimen aims to boost the body's natural defenses, offering a promising new strategy for tackling liver cancer.

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

Research has shown that using tremelimumab and durvalumab together offers significant benefits for liver cancer patients. One study found that this combination helped one in five patients live for five years. These drugs enhance the immune system's ability to fight cancer cells. In this trial, participants will receive BC3402 alongside tremelimumab and durvalumab. BC3402 is a new antibody not yet approved by the FDA. It is designed to enhance these effects by targeting a specific protein that aids cancer growth. Early research suggests that combining BC3402 with tremelimumab and durvalumab may lead to a stronger response against tumors. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with hepatocellular carcinoma, a type of liver cancer. Participants should meet specific health criteria set by the study's guidelines but these are not detailed here.

Inclusion Criteria

I cannot have surgery for my liver cancer and it's been over 28 days since my last local treatment.

My liver cancer diagnosis was confirmed through a tissue examination.

I have not had any treatments for my advanced liver cancer that can't be removed by surgery.

Exclusion Criteria

I have not had hepatic encephalopathy in the last year.

I have had bleeding in my stomach or esophagus in the last year.

I haven't had radiation on over 30% of my bone marrow in the last month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in (Phase Ib)

Safety lead-in study part to confirm the tolerable dose (RP2D) of BC3402 in combination with tremelimumab and durvalumab

8-12 weeks

Efficacy Study (Phase II)

Evaluate preliminary efficacy of the study regimen in a single arm, two stage Minimax design

24-48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years post end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• BC3402
• Durvalumab
• Tremelimumab

Trial Overview The trial is testing the safety and effectiveness of an experimental drug called BC3402 in combination with Tremelimumab and Durvalumab to treat liver cancer.

How Is the Trial Designed?

Group I: BC3402 to tremelimumab plus durvalumab Experimental Treatment 3 Interventions

The study consists of two parts: a safety lead-in study part (Phase Ib) to confirm the tolerable dose (RP2D) of BC3402 in combination with T+D followed by an efficacy study part (Phase II) to evaluate preliminary efficacy of the study regimen in a single arm, two stage Minimax design. Note that participants who are treated at the RP2D in the Phase Ib study part will automatically be part of the Phase II study part.

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

The single-dose regimen of 300 mg tremelimumab combined with durvalumab (STRIDE) shows a favorable benefit-risk profile for patients with unresectable hepatocellular carcinoma (uHCC), as demonstrated in phase I/II and phase III studies.

Higher exposure to tremelimumab is associated with longer overall survival in patients, with those having minimum serum drug concentrations above the median living significantly longer (18.99 months) compared to those below the median (10.97 months), although this relationship may be influenced by other patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-Response Analyses of Tremelimumab Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma. Song, X., Kelley, RK., Khan, AA., et al.[2023]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

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]

The FDA approved tremelimumab in combination with durvalumab for treating unresectable hepatocellular carcinoma based on the HIMALAYA study, which showed a significant improvement in overall survival (OS) compared to sorafenib, with a median OS of 16.4 months versus 13.8 months.

Common adverse reactions in patients receiving the combination treatment included rash, fatigue, diarrhea, and abdominal pain, occurring in 20% or more of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. Patel, TH., Brewer, JR., Fan, J., et al.[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]

Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.

In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. Keam, SJ.[2023]

The combination of tremelimumab and durvalumab (T300 + D) showed the highest overall survival rate (18.7 months) and objective response rate (24.0%) among patients with unresectable hepatocellular carcinoma, indicating its potential as an effective treatment option.

All treatment regimens were generally well-tolerated, but T300 + D had the most favorable safety profile, with a significant association between early CD8+ lymphocyte expansion and treatment response, suggesting a promising mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. Kelley, RK., Sangro, B., Harris, W., 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. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK599983/

Tremelimumab (Imjudo) in Combination With Durvalumab ... ... tremelimumab in combination with durvalumab resulted in added clinical benefit in adult patients with unresectable hepatocellular carcinoma. The HIMALAYA ...

2. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2024/imfinzi-plus-imjudo-demonstrated-unprecedented-overall-survival-alc-with-one-in-five-patients-surviving-five-years-himalaya-phase-iii-trial.html

Imfinzi plus Imjudo demonstrated unprecedented overall ... Imfinzi plus Imjudo demonstrated unprecedented overall survival in advanced liver cancer with one in five patients surviving five years in ...

3. imfinzihcp.com imfinzihcp.com/hcc/unresectable/efficacy.html

Efficacy and Clinical Trial Data for ... Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06608940

BC3402 w/ Tremelimumab + Durvalumab (STRIDE) in ... BC3402 is a TIM3 targeting inhibitory humanized IgG4 subtype monoclonal antibody which displays synergistic anti-tumor effects when combined with agents ...

5. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2023/PC0308-Imfinzi-and-Imjudo-Combined-Report.pdf

Tremelimumab (Imjudo) in Combination With Durvalumab ( ... BCLC = Barcelona Clinic Liver Cancer; HCC = hepatocellular carcinoma; STRIDE = single-dose tremelimumab in combination with regular-interval ...

6. withpower.com withpower.com/trial/phase-2-carcinoma-hepatocellular-11-2024-cf884

BC3402 + Tremelimumab + Durvalumab for Liver Cancer The combination of Tremelimumab and Durvalumab has been studied for safety in various cancers, including liver cancer. Common side effects include rash, fatigue ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10841291/

FDA Approval Summary: Tremelimumab in combination ... The median OS was 16.4 months (95% CI, 14.2 to 19.6) with tremelimumab in combination with durvalumab and 13.8 months (95% CI, 12.3 to 16.1) with sorafenib.

8. ecancer.org ecancer.org/en/video/12451-durvalumab-and-tremelimumab-show-manageable-safety-in-poor-prognosis-hcc

Durvalumab and tremelimumab show manageable safety ... Initial results show a 19.1% rate of significant adverse events, but treatment discontinuation and mortality rates remain low, indicating a ...

9. targetedonc.com targetedonc.com/view/tremelimumab-plus-durvalumab-turns-heads-with-updated-five-year-data-in-uhcc

Tremelimumab Plus Durvalumab Turns Heads With ... The HIMALAYA study showed that the combination of tremelimumab and durvalumab significantly improved overall survival in patients with hepatocellular carcinoma.