ALN-BCAT + Pembrolizumab for Liver Cancer

Recruiting at 20 trial locations

Overseen By Alnylam Clinical Trial Information Line

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Alnylam Pharmaceuticals

Must not be taking: Anti-cancer, Investigational drugs

Disqualifiers: Fibrolamellar HCC, Symptomatic extrahepatic, others

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

Compensation: Varies

Number of Visits: Unknown

158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for liver cancer, specifically hepatocellular carcinoma (HCC). Researchers aim to determine the safety and tolerability of the experimental drug ALN-BCAT, both alone and in combination with pembrolizumab, a cancer treatment. They also assess the effectiveness of this combination against tumors. Individuals who have undergone at least one round of systemic therapy for liver cancer and possess a specific genetic mutation called a WNT-pathway mutation may be suitable candidates. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received any anti-cancer therapy or investigational drugs within 3 weeks before starting the study.

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

Research has shown that ALN-BCAT remains in the early testing stages. Currently, scientists focus on its safety and tolerability. Detailed safety information is not widely available yet, as studies are ongoing.

In contrast, pembrolizumab, used with ALN-BCAT in this trial, is a well-known treatment. The FDA has approved it for various cancers, indicating general safety, though it can cause side effects like tiredness or a rash.

Since this trial with ALN-BCAT is in its early phase, the main goals are to determine the right dose and identify any side effects. Researchers will closely monitor participants to ensure their safety. It is important to remember that new treatments often require time to fully understand their safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ALN-BCAT for liver cancer because it offers a novel approach by potentially targeting the disease at a molecular level. Unlike traditional treatments like chemotherapy and surgery, ALN-BCAT is designed to interfere with specific pathways that cancer cells use to grow, which might result in more effective and less toxic treatment options. Additionally, when combined with pembrolizumab, an immune checkpoint inhibitor, it could enhance the immune system’s ability to fight cancer more effectively. This combination therapy could lead to better outcomes for patients who currently have limited options.

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

Research has shown that ALN-BCAT could be a promising treatment for liver cancer. It targets a protein called beta-catenin, which often aids tumor growth. Early studies demonstrated that ALN-BCAT can block this process, potentially stopping or slowing tumor growth in liver cancer patients. In this trial, some participants will receive ALN-BCAT alone, while others will receive a combination of ALN-BCAT and Pembrolizumab. Pembrolizumab, an approved treatment, helps the body's immune system fight cancer. Combining ALN-BCAT with Pembrolizumab aims to boost the immune response while targeting the tumor growth process. Although research continues, the mechanisms of these treatments and early results suggest they could be beneficial when used together. ^{1 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with hepatocellular carcinoma, a type of liver cancer. Participants should meet specific health criteria set by the study's guidelines to be eligible.

Inclusion Criteria

My liver cancer diagnosis is confirmed by a doctor's evaluation or tests.

My liver function is mildly to moderately impaired.

I have received treatment for cancer that cannot be surgically removed.

Exclusion Criteria

My liver cancer is of a specific type (fibrolamellar, sarcomatoid, or mixed).

I have symptoms from cancer that has spread outside my liver.

I haven't taken any cancer treatment or trial drugs in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Characterize the safety and tolerability of ALN-BCAT as monotherapy and in combination with pembrolizumab; determine the recommended dose(s) for expansion

8-12 weeks

Dose Expansion

Evaluate the antitumor activity of ALN-BCAT as monotherapy and in combination with pembrolizumab; characterize the safety and tolerability

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ALN-BCAT
• Pembrolizumab

Trial Overview The trial is testing ALN-BCAT alone and in combination with Pembrolizumab. It aims to find safe dosages, understand side effects, and assess how well these treatments work against liver cancer.

How Is the Trial Designed?

Group I: Monotherapy: Dose Expansion Experimental Treatment 1 Intervention

Patients will be administered multiple doses of ALN-BCAT.

Group II: Monotherapy: Dose Escalation Experimental Treatment 1 Intervention

Patients will be administered multiple doses of ALN-BCAT.

Group III: Combination Therapy: Dose Expansion Experimental Treatment 2 Interventions

Patients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.

Group IV: Combination Therapy: Dose Escalation Experimental Treatment 2 Interventions

Patients will be administered multiple doses of ALN-BCAT in combination with pembrolizumab.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Published Research Related to This Trial

In a study of 120 patients with advanced hepatocellular carcinoma (HCC), both nivolumab and pembrolizumab showed comparable efficacy, with response rates of 8.0% for pembrolizumab and 7.4% for nivolumab, and similar median progression-free survival (PFS) of 2.7 months and 2.9 months, respectively.

The median overall survival (OS) was longer for nivolumab at 10.8 months compared to 8.1 months for pembrolizumab, but this difference was not statistically significant, indicating that both treatments are similarly effective in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world comparison of pembrolizumab and nivolumab in advanced hepatocellular carcinoma. Chen, YH., Tsai, CH., Chen, YY., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a phase II trial involving 51 patients with advanced hepatocellular carcinoma (HCC) who had not received prior systemic therapy, pembrolizumab demonstrated a 16% objective response rate, indicating its potential effectiveness in this patient population.

The treatment showed a median overall survival of 17 months and a median duration of response of 16 months, with a safety profile that included grade ≥3 treatment-related adverse events in 16% of patients, suggesting it is tolerable for use in advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Monotherapy for Previously Untreated Advanced Hepatocellular Carcinoma: Data from the Open-Label, Phase II KEYNOTE-224 Trial. Verset, G., Borbath, I., Karwal, M., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

The combination of pembrolizumab and carboplatin was found to be well-tolerated and showed activity in patients with recurrent platinum-resistant ovarian cancer, with a median overall survival of 11.3 months.

Patients with a higher ratio of peripheral CD8+PD1+Ki67+ T cells to tumor burden had significantly longer overall survival, suggesting this ratio could help identify those who may benefit more from this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab with low-dose carboplatin for recurrent platinum-resistant ovarian, fallopian tube, and primary peritoneal cancer: survival and immune correlates. Liao, JB., Gwin, WR., Urban, RR., et al.[2022]

In a phase 2 trial involving 104 patients with advanced hepatocellular carcinoma who had previously been treated with sorafenib, pembrolizumab demonstrated an objective response rate of 17%, indicating its potential efficacy as a treatment option for this patient population.

While 73% of patients experienced treatment-related adverse events, most were manageable, with serious events occurring in 15% of patients, suggesting that pembrolizumab is generally tolerable for patients with advanced liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Zhu, AX., Finn, RS., Edeline, J., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has shown significant efficacy in treating advanced melanoma, demonstrating superior progression-free survival compared to chemotherapy in Phase II trials and improved overall survival in Phase III trials.

The treatment is generally well tolerated with a favorable safety profile, though common side effects include fatigue and rash, while less frequent but serious immune-related adverse events can occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in the management of metastatic melanoma. Spain, L., Younger, E., Hatipoglu, E., et al.[2020]

In a phase III study involving 413 patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib, pembrolizumab showed a median overall survival of 13.9 months compared to 10.6 months for placebo, indicating its potential effectiveness as a treatment option.

While pembrolizumab demonstrated improved overall survival and progression-free survival compared to placebo, the study noted a higher incidence of grade 3 or higher adverse events, suggesting a need to weigh the benefits against the risks when considering this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. Finn, RS., Ryoo, BY., Merle, P., et al.[2020]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a phase III trial involving 453 patients with advanced hepatocellular carcinoma (HCC), pembrolizumab significantly improved overall survival (14.6 months vs. 13.0 months for placebo) and progression-free survival (2.6 months vs. 2.3 months for placebo).

The objective response rate (ORR) was notably higher in the pembrolizumab group (12.7%) compared to the placebo group (1.3%), although treatment-related adverse events were more common in the pembrolizumab group (66.9% vs. 49.7% for placebo).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Versus Placebo as Second-Line Therapy in Patients From Asia With Advanced Hepatocellular Carcinoma: A Randomized, Double-Blind, Phase III Trial. Qin, S., Chen, Z., Fang, W., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06600321

NCT06600321 | A Study to Evaluate ALN-BCAT in Patients ... The purpose of the dose expansion part of the of the study is to evaluate the antitumor activity of ALN-BCAT as monotherapy and in combination with ...

2. clinicaltrials.alnylam.com clinicaltrials.alnylam.com/trials/6600321

ALN-BCAT-001 - Alnylam Clinical Trials The purpose of the dose expansion part of the of the study is to evaluate the antitumor activity of ALN-BCAT as monotherapy and in combination with ...

3. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb241614

CLINICAL TRIAL / NCT06600321 A Phase 1 Study of ALN-BCAT as Monotherapy and in Combination with Pembrolizumab in Patients With Advanced or Metastatic Hepatocellular Carcinoma.

4. cancer.gov cancer.gov/clinicaltrials/NCI-2024-08329

A Study to Evaluate ALN-BCAT in Patients With ... The purpose of the dose expansion part of the of the study is to evaluate the antitumor activity of ALN-BCAT as monotherapy and in combination with ...

5. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-1-study-aln-bcat-monotherapy-and-combination-pembrolizumab-inpatients-advanced-or-metastatic-hepatocellular-carcinoma

A Phase 1 Study of ALN-BCAT as Monotherapy and in ... The purpose of this study is to test the safety of an investigational drug called ALN-BCAT, and find out what effects, if any, ALN-BCAT has on people with your ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/532760

A Study to Evaluate ALN-BCAT in Patients With ... The purpose of the dose escalation part of the study is to characterize the safety and tolerability of ALN-BCAT as monotherapy and in combination with ...

7. investors.alnylam.com investors.alnylam.com/press-release?id=27841

Alnylam Pharmaceuticals Press Release | Dec 13, 2023 Alnylam scientists will also present promising preclinical data with ALN-BCAT, an investigational RNAi therapeutic targeting β-catenin for the ...