GT90001 + Nivolumab for Liver Cancer

Not currently recruiting at 4 trial locations

Overseen By Ting Huang, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Suzhou Kintor Pharmaceutical Inc,

Must not be taking: Immune checkpoint inhibitors, Tyrosine kinase inhibitors

Disqualifiers: CNS metastases, Transplant history, Active infections, Others

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

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

Compensation: Varies

Number of Visits: 2

Duration: Approximately 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the combined effects of two treatments, GT90001 (a new potential drug) and Nivolumab, for individuals with advanced liver cancer who did not respond well to initial treatments. Both medications are administered through infusions every two weeks to determine if they can better manage the cancer. Suitable candidates for this trial have advanced liver cancer, could not undergo surgery, and have not responded to earlier immune therapies. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have received certain treatments like immune checkpoint inhibitors or tyrosine kinase inhibitors within four weeks before starting the study treatment.

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

Research shows that the combination of GT90001 and Nivolumab is generally safe. Studies have found that this combination has a manageable safety profile. While some side effects may occur, they are not severe and can be controlled or treated.

The trials primarily focus on ensuring the treatment does not cause harm. Patients have responded well, with no unexpected problems reported. For those considering joining a trial with this combination, existing research suggests it is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for liver cancer?

Researchers are excited about GT90001 combined with Nivolumab for liver cancer because this duo offers a novel approach compared to traditional treatments. Most current treatments for liver cancer, such as sorafenib or lenvatinib, focus on inhibiting tumor growth through targeting specific proteins or pathways. However, GT90001 works differently by potentially enhancing the immune system's ability to fight cancer, while Nivolumab is an immune checkpoint inhibitor that helps unleash immune cells to attack cancer cells. This combination could result in a more robust and sustained anti-tumor response, offering hope for improved outcomes in liver cancer patients.

What evidence suggests that this trial's treatments could be effective for advanced hepatocellular carcinoma?

Research has shown that combining GT90001 with nivolumab, which participants in this trial will receive, may help fight tumors in people with advanced liver cancer. Studies indicate that this combination is generally safe and well-tolerated by patients. Early results suggest it can shrink tumors, offering hope for those who haven't had success with other treatments. These findings are promising for people with advanced liver cancer who have few options after initial treatments. While more research is needed, current evidence supports the potential effectiveness of this treatment combination. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer (aHCC) who can't have or didn't improve with first-line immune treatments. They should be in relatively good health (Child-Pugh A, ECOG 0-1), not have had certain other cancers recently, no serious infections or organ transplants, and a life expectancy over 3 months.

Inclusion Criteria

Have a predicted life expectancy of greater than 3 months

My liver function is good, with a Child-Pugh score of 6 or less.

My liver cancer is at an advanced stage and cannot be treated with local therapies.

Exclusion Criteria

I received immune therapy less than 4 weeks ago.

I have another cancer that is getting worse or was treated in the last 3 years.

I have or had cancer 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

Treatment

Participants receive GT90001 and Nivolumab infusions every two weeks

Approximately 2 years

Infusions every 2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GT90001
• Nivolumab

Trial Overview The study tests GT90001 combined with Nivolumab in patients whose liver cancer has worsened after or couldn’t tolerate initial immune checkpoint inhibitors. It's an open-label phase II trial where both drugs are given by infusion every two weeks to a total of 105 participants.

How Is the Trial Designed?

Group I: GT90001+Nivolumab Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Suzhou Kintor Pharmaceutical Inc,

Lead Sponsor

Trials

18

Recruited

3,900+

Published Research Related to This Trial

In a retrospective analysis of 34 advanced HCC patients treated with nivolumab, the treatment was found to be safe, with only 5.9% experiencing grade 3 toxicities, indicating a manageable safety profile.

The overall survival for patients was relatively short, with a median of 7.5 weeks, and those with Child-Pugh B stage disease had significantly poorer outcomes, suggesting that nivolumab's efficacy may be limited in patients with advanced liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers. Finkelmeier, F., Czauderna, C., Perkhofer, L., et al.[2020]

In a study of 11 patients with advanced hepatocellular carcinoma (HCC), nivolumab therapy demonstrated a high disease control rate of 81.8% and an objective response rate of 63.6%, indicating its efficacy as a treatment option.

No adverse effects related to nivolumab were reported, suggesting a favorable safety profile, especially for patients who did not respond to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma. Feng, D., Hui, X., Shi-Chun, L., et al.[2022]

A patient with stage IV melanoma treated with nivolumab (an anti-PD-L1 antibody) experienced rare liver toxicity, which was linked to an acute exacerbation of previously undiagnosed hepatitis B.

The case highlights the importance of conducting serological viral screening for hepatitis B before starting treatment with immune checkpoint inhibitors to prevent severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroid-refractory immune related hepatitis may hide viral re-activation. Citarella, F., Galletti, A., Russano, M., et al.[2020]

Nivolumab, a PD-1 inhibitor, showed durable responses and increased overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC), with a median OS of 28.1 months for patients with PD-L1 expression ≥1% compared to 16.6 months for those with <1%.

The study found that higher expression of PD-1 and PD-L1, along with specific inflammatory gene signatures, were associated with improved survival and response to treatment, suggesting that the immune response plays a significant role in the effectiveness of nivolumab in HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. Sangro, B., Melero, I., Wadhawan, S., et al.[2022]

Immune checkpoint inhibitors like nivolumab have revolutionized cancer treatment but can lead to serious autoimmune-like side effects known as immune-related adverse events (irAEs).

This study highlights a specific case of severe liver injury linked to nivolumab in a glioblastoma patient, emphasizing the need for better understanding and management of these potential toxicities to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathological characterization of nivolumab-related liver injury in a patient with glioblastoma. Simonelli, M., Di Tommaso, L., Baretti, M., et al.[2018]

A retrospective analysis of adverse events related to PD-1/PD-L1 inhibitors revealed a significant association between Pembrolizumab and hepatitis B reactivation (HBVr), with a reporting odds ratio of 2.32, indicating a higher risk compared to other treatments.

No cases of HBVr were reported with Ipilimumab or Avelumab, suggesting that not all immune checkpoint inhibitors carry the same risk, highlighting the need for further prospective studies to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. Burns, EA., Muhsen, IN., Anand, K., et al.[2023]

In a study of 71 patients with advanced hepatocellular carcinoma, the combination of nivolumab and cabozantinib showed promising antitumor activity, with an objective response rate of 17% for the doublet therapy and 29% for the triplet therapy including ipilimumab.

Both treatment combinations had manageable safety profiles, with 50% of patients in the doublet arm and 74% in the triplet arm experiencing grade 3-4 treatment-related adverse events, but no treatment-related deaths were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Cabozantinib With or Without Ipilimumab for Advanced Hepatocellular Carcinoma: Results From Cohort 6 of the CheckMate 040 Trial. Yau, T., Zagonel, V., Santoro, A., et al.[2023]

In a phase 1/2 study involving 148 patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib, the combination of nivolumab and ipilimumab showed a promising objective response rate of 32% in one treatment arm, indicating potential efficacy for this patient population.

The treatment regimen was generally manageable in terms of safety, although 94% of patients in one arm experienced treatment-related adverse events, highlighting the need for careful monitoring; notably, this combination therapy received accelerated approval in the US based on these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial. Yau, T., Kang, YK., Kim, TY., et al.[2022]

Nivolumab, an anti-PD-1 antibody, was administered to a 63-year-old female patient with metastatic melanoma after renal transplantation, highlighting the potential for anti-tumor activity in high-risk patients, despite the challenges of concurrent immunosuppression.

The patient experienced acute renal allograft rejection and renal failure shortly after starting nivolumab, indicating significant risks associated with this treatment in transplant recipients, but she later showed a positive clinical response after re-challenging with nivolumab while on hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. Ong, M., Ibrahim, AM., Bourassa-Blanchette, S., et al.[2023]

Nivolumab has been demonstrated to be an effective treatment for hepatocellular carcinoma (HCC), indicating its potential as a therapeutic option for this type of liver cancer.

The treatment is also reported to be safe, suggesting that it can be administered with a manageable side effect profile for patients with HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Programmed death-1 therapy in advanced hepatocellular carcinoma: A real-world experience. Al Jarroudi, O., Chaabouni, H., Ulusakarya, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10588186/

Combination of GT90001 and nivolumab in patients with ... GT90001 plus nivolumab has a manageable safety profile and promising anti-tumor activity in patients with advanced HCC.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37858184

Combination of GT90001 and nivolumab in patients with ... Conclusions: GT90001 plus nivolumab has a manageable safety profile and promising anti-tumor activity in patients with advanced HCC. Trial ...

3. targetedonc.com targetedonc.com/view/phase-2-trial-of-gt90001-plus-nivolumab-enrolls-first-patient-with-advanced-hcc

Phase 2 Trial of GT90001 Plus Nivolumab Enrolls First ... The phase 2 clinical trial of the combination therapy, GT90001 and nivolumab, for the treatment of patients with advanced hepatocellular ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03893695

NCT03893695 | Combination of GT90001 and Nivolumab ... The primary objective of the study is to determine the safety and tolerability of GT90001 in combination with nivolumab in subjects with ...

5. opdivohcp.com opdivohcp.com/efficacy/hcc

Efficacy Data for Hepatocellular Carcinoma (HCC) OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone.

6. omicsdi.org omicsdi.org/dataset/biostudies-literature/S-EPMC10588186

Combination of GT90001 and nivolumab in patients with ... Patients in dose-expansion stage received the RP2D of GT90001 plus nivolumab. Primary endpoint was safety. Key secondary endpoint was objective response rate ( ...