Personalized Cancer Vaccine + Pembrolizumab for Liver Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a personalized cancer vaccine (GNOS-PV02) combined with pembrolizumab, a type of immunotherapy, for people with liver cancer. Researchers seek to determine if this combination can slow the disease or improve treatment outcomes. The trial seeks participants diagnosed with liver cancer that has not responded to other local treatments. Those with serious liver cancer who are currently taking or eligible for certain medications might find this trial suitable. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Research has shown that the combination of GNOS-PV02, INO-9012, and pembrolizumab has been tested for human safety. In these studies, the treatment was generally well-tolerated, meaning most people could handle it without major issues. However, like many cancer treatments, some side effects were reported.

The studies focused on the safety of this combination for patients with advanced liver cancer and found it could be used without causing severe problems. Some patients did experience side effects, but these were typical for cancer treatments.

It's important to note that pembrolizumab, one of the components, is already approved by the FDA for other cancers, which adds confidence in its safety. Overall, the treatment has shown promise in being safe enough for more testing in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining GNOS-PV02 with INO-9012 and Pembrolizumab for treating liver cancer because of its unique approach. Unlike standard treatments like tyrosine kinase inhibitors, this experimental treatment leverages personalized cancer vaccines to boost the immune response specifically against the patient's tumor. GNOS-PV02 is designed to tailor the immune attack to the individual's cancer profile, potentially increasing effectiveness. Additionally, Pembrolizumab, a type of immunotherapy, works by blocking a protein that prevents the immune system from attacking cancer cells. This combination aims to not only directly target the cancer but also enhance the overall immune defense, offering hope for better outcomes where other treatments might have been less effective.

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

Research shows that a new treatment combining the personalized vaccine GNOS-PV02, INO-9012, and pembrolizumab may be promising for liver cancer. In earlier studies, 40.7% of patients experienced a reduction of at least 50% in circulating tumor DNA (ctDNA), indicating a strong effect on the cancer. This treatment uses GNOS-PV02 to train the immune system to attack cancer cells, INO-9012 to enhance this response, and pembrolizumab to help the immune system find and destroy cancer more effectively. Early results suggest this method could lead to lasting improvements for patients with advanced liver cancer, offering hope for better outcomes in this difficult-to-treat condition. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04251117

GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38584166/

Personalized neoantigen vaccine and pembrolizumab in ... We present results from a single-arm, open-label, phase 1/2 study of a DNA plasmid PTCV (GNOS-PV02) encoding up to 40 neoantigens coadministered ...

3. clin.larvol.com clin.larvol.com/trial-detail/NCT04251117

GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 ... Reductions of at least 50% versus baseline in patient ctDNA, an exploratory endpoint, were seen in 40.7% of patients (11 of 27 patients for whom the full data ...

4. geneostx.com geneostx.com/geneos-personalized-neoantigen-targeting-vaccine-gnos-pv02-to-be-utilized-in-innovative-gt-30-hepatocellular-carcinoma-trial/

Geneos Personalized Neoantigen-Targeting Vaccine ... In the trial, GNOS-PV02 will be combined with a DNA plasmid encoded cytokine immunomodulator IL-12 (INO-9012) and standard of care PD-1 ...

5. onclive.com onclive.com/view/personalized-neoantigen-vaccine-induces-continued-responses-in-pretreated-advanced-hcc

Personalized Neoantigen Vaccine Induces Continued ... The study is evaluating the safety, immunogenicity, and efficacy of PTCV plus pembrolizumab (Keytruda) in 36 patients with unresectable or ...