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

43 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination BC3402, Tremelimumab, and Durvalumab for liver cancer?

The combination of tremelimumab and durvalumab has been shown to improve overall survival in patients with liver cancer that cannot be surgically removed, as demonstrated in the HIMALAYA study. This study found that patients receiving this combination lived longer compared to those receiving another treatment called sorafenib. ^{1 2 3 4 5}

What safety data exists for the combination of BC3402, Tremelimumab, and Durvalumab in humans?

The combination of Tremelimumab and Durvalumab has been studied for safety in various cancers, including liver cancer. Common side effects include rash, fatigue, diarrhea, itching, muscle pain, and abdominal pain. Serious side effects (Grade 3 or higher) occurred in about 32.6% of patients, which is higher compared to Durvalumab alone. ^{1 2 4 6 7}

What makes the BC3402 + Tremelimumab + Durvalumab drug unique for liver cancer?

This drug combination is unique because it includes tremelimumab and durvalumab, which are immune checkpoint inhibitors that help the immune system attack cancer cells. The combination has shown improved survival rates in patients with unresectable liver cancer compared to standard treatments like sorafenib. ^{1 2 3 4 8}

What is the purpose of this trial?

The purpose of this study is to test the safety and efficacy of an investigational (experimental) product called BC3402. This product is considered experimental because it is not approved by the U.S. Food and Drug Administration (FDA).

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

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

FDA Approval Summary: Tremelimumab in combination with durvalumab for the treatment of patients with unresectable hepatocellular carcinoma. [2023]

2. United States 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. [2022]

3. United States 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. [2022]

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

Tremelimumab: First Approval. [2023]

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

Dual Immunotherapy Makes Strides against HCC. [2022]

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

Exposure-Response Analyses of Tremelimumab Monotherapy or in Combination with Durvalumab in Patients with Unresectable Hepatocellular Carcinoma. [2023]

8. 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]