GT90001 + Nivolumab for Liver Cancer

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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a global phase II, open label study in the subjects with Advanced Hepatocellular Carcinoma (aHCC) who were intolerant or had progressed after or intolerant to first-line Immune Checkpoint Inhibitors (ICI) such as Atezolizumab plus Bevacizumab, or ICI plus Tyrosine Kinase Inhibitor (TKI). Based on published and first-hand experience with the safety and tolerability of both GT90001 and Nivolumab, the proposed dose is GT90001 7 mg/kg in combination with Nivolumab 240 mg, infusion every two weeks. This study will enroll a total of 105 subjects to receive combinational therapy of Nivolumab and GT90001. • Nivolumab 240 mg will first be administered by intravenous infusion over 30 minutes, then 30 minutes later, give intravenous infusion of GT90001 7.0 mg/kg over 60 min, once every two weeks.

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.

What data supports the effectiveness of the drug GT90001 + Nivolumab for liver cancer?

Research shows that Nivolumab, a part of the treatment, has been effective in treating advanced liver cancer by improving survival and providing durable responses. It has been used successfully in combination with other drugs for liver cancer, suggesting potential benefits when combined with GT90001. ^{1 2 3 4 5}

Is the combination of GT90001 and Nivolumab safe for humans?

Nivolumab, a part of the treatment, can cause immune-related side effects, including liver injury and hepatitis B reactivation, which are rare but can be serious. It's important to monitor for these effects and manage them properly to ensure safety. ^{6 7 8 9 10}

How is the drug combination of GT90001 and nivolumab unique for liver cancer?

The combination of GT90001 and nivolumab is unique for liver cancer because GT90001 is an anti-ALK-1 monoclonal antibody, which targets a specific protein involved in tumor growth, and when combined with nivolumab, a PD-1 inhibitor that helps the immune system attack cancer cells, it offers a novel approach to treating advanced hepatocellular carcinoma. ^{1 5 11 12 13}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Initial experience of anti-PD1 therapy with nivolumab in advanced hepatocellular carcinoma. [2022]

2. United States 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. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Association of inflammatory biomarkers with clinical outcomes in nivolumab-treated patients with advanced hepatocellular carcinoma. [2022]

4. United States 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. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Feasibility and safety of nivolumab in advanced hepatocellular carcinoma: real-life experience from three German centers. [2020]

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

Hepatitis B Virus Reactivation in Cancer Patients Treated With Immune Checkpoint Inhibitors. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Steroid-refractory immune related hepatitis may hide viral re-activation. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Successful mycophenolate mofetil treatment of a patient with severe steroid-refractory hepatitis evoked by nivolumab plus ipilimumab treatment for relapsed bladder cancer. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Pathological characterization of nivolumab-related liver injury in a patient with glioblastoma. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Combination of GT90001 and nivolumab in patients with advanced hepatocellular carcinoma: a multicenter, single-arm, phase 1b/2 study. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Anti-Programmed death-1 therapy in advanced hepatocellular carcinoma: A real-world experience. [2021]