Personalized Cancer Vaccine + Pembrolizumab for Liver Cancer

Recruiting at 2 trial locations

Overseen By Clinical Admin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Geneos Therapeutics

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Autoimmune disease, Transplant, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Phase I/IIa

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single-arm, open-label, multi-site Phase I/IIa study of a personalized neoantigen DNA vaccine (GNOS-PV02) and plasmid encoded IL-12 (INO-9012) in combination with pembrolizumab (MK-3475) in subjects with histologically or cytologically confirmed diagnosis of HCC based on pathology report.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on antiviral therapy for hepatitis B, you must continue it during the study. Also, you cannot have taken sorafenib or lenvatinib within 14 days before starting the study treatment.

What data supports the effectiveness of the drug Pembrolizumab for liver cancer?

Research shows that Pembrolizumab, a drug that helps the immune system fight cancer, has shown promising results in patients with advanced liver cancer, particularly those who have already received other treatments. Studies indicate it can be effective in improving outcomes for these patients. ^{1 2 3 4 5}

Is the treatment of Personalized Cancer Vaccine + Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA, has been studied in various conditions and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as inflammation of the lungs (pneumonitis) and liver (hepatitis). ^{2 5 6 7 8}

What makes the treatment with Personalized Cancer Vaccine + Pembrolizumab unique for liver cancer?

This treatment combines a personalized cancer vaccine with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. The combination aims to enhance the body's immune response specifically against liver cancer, which is different from standard treatments that may not be personalized or use pembrolizumab alone. ^{1 5 6 7 9}

Eligibility Criteria

Adults with advanced liver cancer (HCC) who haven't had certain treatments, can provide a tissue sample for the vaccine, have an ECOG performance status of 0 or 1, and are expected to live more than 6 months. They must not be pregnant or breastfeeding and agree to use contraception. Excluded are those with recent encephalopathy, organ transplants, lung disease, active infections like HIV/HBV without treatment plans, or other conditions that could interfere with the study.

Inclusion Criteria

I am eligible for or already receiving sorafenib or lenvatinib as my first treatment.

I am receiving or have received treatment for hepatitis B or C as required.

Be willing to use an adequate method of contraception for the course of the study through 150 days after the last dose of study drug (male and female subjects of childbearing potential) Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

Exclusion Criteria

My doctor thinks this treatment could worsen my other health issues.

My scans show cancer has spread to my brain or its coverings.

I have had treatment for liver cancer, but not with sorafenib or lenvatinib.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GNOS-PV02, INO-9012, and Pembrolizumab upon disease progression or intolerance to TKI

Phase I/IIa

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• GNOS-PV02
• INO-9012
• Pembrolizumab

Trial Overview The trial is testing a personalized neoantigen DNA vaccine (GNOS-PV02), plasmid encoded IL-12 (INO-9012), and pembrolizumab in patients with HCC. It's an open-label Phase I/IIa study where all participants receive this combination therapy to see how well it works against liver cancer.

Participant Groups

Group I: GNOS-PV02 + INO-9012 + Pembrolizumab Experimental Treatment 4 Interventions

First line therapy with standard of care tyrosine kinase inhibitors (TKI) during which patient-specific GNOS-PV02 will be manufactured. GNOS-PV02 + INO-9012 + Pembrolizumab will be administered upon disease progression or intolerance to TKI.

Who Is Running the Clinical Trial?

Geneos Therapeutics

Lead Sponsor

Trials

2

Recruited

50+

Findings from Research

In a phase 2 trial involving 12 patients with advanced osteosarcoma, pembrolizumab showed no clinical benefit at 18 weeks, with all patients experiencing disease progression and a median overall survival of only 6.6 months.

Despite the lack of significant antitumor activity, pembrolizumab was well-tolerated, with no treatment-related deaths or severe adverse events, suggesting it may be safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. Boye, K., Longhi, A., Guren, T., 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]

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]

In a study of 29 patients with advanced hepatocellular carcinoma (HCC) treated with pembrolizumab, the overall response rate was 32%, with one complete response and eight partial responses, indicating that pembrolizumab can be an effective treatment option for this patient group.

The treatment was generally well-tolerated, with reversible grade 3/4 adverse events, and high baseline levels of TGF-β in plasma were identified as a potential predictive biomarker for poor treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma. Feun, LG., Li, YY., Wu, C., et al.[2020]

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]

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 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 unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial. [2022]

2. England 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. [2022]

3. United States 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. [2023]

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

Phase 2 study of pembrolizumab and circulating biomarkers to predict anticancer response in advanced, unresectable hepatocellular carcinoma. [2020]

5. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

7. United States 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. [2020]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

A T-cell-dependent antibody response study using a murine surrogate anti-PD-1 monoclonal antibody as an alternative to a non-human primate model. [2021]