PRTH-101 + Pembrolizumab for Advanced Cancer

Recruiting at 8 trial locations

Overseen By Joseph Paul Eder, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Incendia Therapeutics

Must not be taking: Systemic steroids, Immunosuppressive therapy

Disqualifiers: Immunodeficiency, Autoimmune disease, CNS tumor, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 4 years

270 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this Open-Label Study is to evaluate the safety and tolerability of PRTH-101 alone or in combination with pembrolizumab in adults with advance or metastatic solid tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like systemic steroids or immunosuppressive therapy within 14 days before starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Research shows that pembrolizumab helps improve survival in patients with advanced melanoma and non-small cell lung cancer. It works by boosting the body's immune response against cancer cells, and has been effective in tumors that express certain proteins like PD-L1. ^{1 2 3 4 5}

What makes the drug PRTH-101 + Pembrolizumab unique for advanced cancer?

PRTH-101 combined with pembrolizumab is unique because it potentially enhances the immune system's ability to fight cancer by targeting different pathways, with pembrolizumab already known for its effectiveness in tumors expressing PD-L1. This combination aims to improve outcomes in cancers that are less responsive to immunotherapy alone. ^{1 6 7 8 9}

Research Team

Joseph Paul Eder, MD

Principal Investigator

Incendia Therapeutics

Eligibility Criteria

Adults with advanced or metastatic solid tumors who have not responded to standard treatments, are ineligible for them, or do not wish to receive them. Participants must be over 18, in good physical condition (ECOG PS 0-1), and have a life expectancy of at least 3 months. They should not be on other cancer trials or treatments and must agree to use birth control. People with certain medical conditions, recent surgeries, ongoing toxicity from past therapies above Grade 1 (except specific cases), active infections like hepatitis or HIV, unstable heart disease, CNS tumor involvement that's untreated/active within the last month are excluded.

Inclusion Criteria

I can carry out all my usual activities without help.

Subject must be willing and able to read, understand, and sign an Informed Consent Form

My advanced cancer cannot be surgically removed, and standard treatments are not suitable for me.

Exclusion Criteria

I have cancer at more than one site in my body.

Subject has any contraindications to the imaging assessments or other study procedures that subjects will be undergoing

Subject has any medical or social condition that, in the opinion of the Investigator, might place a subject at increased risk, affect compliance, or confound safety or other clinical study data interpretation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PRTH-101 alone or in combination with pembrolizumab to evaluate safety, tolerability, and anti-tumor activity

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• PRTH-101

Trial Overview The trial is testing PRTH-101 alone or combined with pembrolizumab in adults with various types of advanced cancers. It aims to assess how safe these treatments are and how well patients tolerate them. The study is open-label which means everyone knows what treatment they're getting.

Participant Groups

Group I: PRTH-101 with Pembrolizumab Experimental Treatment 2 Interventions

Combo therapy

Group II: PRTH-101 Experimental Treatment 1 Intervention

Mono-therapy

Who Is Running the Clinical Trial?

Incendia Therapeutics

Lead Sponsor

Trials

1

Recruited

270+

Parthenon Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

270+

Findings from Research

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

In the KEYNOTE-189 study involving 616 patients with metastatic non-squamous non-small-cell lung cancer, the combination of pembrolizumab and pemetrexed-platinum significantly maintained quality of life (GHS/QOL) scores compared to placebo, with a notable improvement at week 21.

Patients receiving pembrolizumab also experienced a longer median time to deterioration in symptoms like cough and chest pain, although this result was not statistically significant, indicating potential benefits in symptom management with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Garassino, MC., Gadgeel, S., Esteban, E., et al.[2020]

In a study of 183 patients with advanced melanoma treated with pembrolizumab, several baseline factors such as active brain metastases, higher total metabolic tumor volume (TMTV), and lower absolute lymphocyte count (ALC) were linked to worse survival outcomes.

TMTV was identified as a more effective predictor of treatment futility compared to other markers like C-reactive protein (CRP) and lactate dehydrogenase (LDH), suggesting that patients with high TMTV may not benefit from pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. Awada, G., Jansen, Y., Schwarze, JK., et al.[2021]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC) expressing PD-L1, pembrolizumab significantly improved median progression-free survival to 10.3 months compared to 6.0 months with chemotherapy, indicating its efficacy as a treatment option.

Patients receiving pembrolizumab also experienced fewer treatment-related adverse events (73.4% vs. 90.0% for chemotherapy), highlighting its safety profile alongside its effectiveness in prolonging survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

This study is investigating the safety and efficacy of pembrolizumab as a first-line treatment for patients aged 75 and older with advanced non-small cell lung cancer (NSCLC) and a high PD-L1 tumor proportion score (≥50%).

The primary goal is to assess progression-free survival, with additional focus on overall survival, response rates, safety, and quality of life, addressing a significant gap in treatment options for elderly patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment rationale and design of the PROLONG study: safety and efficacy of pembrolizumab as first-line therapy for elderly patients with non-small cell lung cancer. Masuda, T., Fujitaka, K., Ishikawa, N., et al.[2022]

In a study of 100 patients with non-small cell lung cancer (NSCLC) treated with pembrolizumab, further stratification of PD-L1 tumor proportion score (TPS) beyond 50% did not significantly affect progression-free survival (PFS).

Smoking status was associated with improved PFS, while prior radiotherapy was linked to decreased PFS, indicating that these factors, along with performance status, may serve as important biomarkers for predicting response to pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. Mander, ES., Merrick, CB., Nicholson, HA., et al.[2023]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab. [2021]

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

Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. [2022]

7. China pubmed.ncbi.nlm.nih.gov

Treatment rationale and design of the PROLONG study: safety and efficacy of pembrolizumab as first-line therapy for elderly patients with non-small cell lung cancer. [2022]

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

Pembrolizumab monotherapy for non-small cell lung cancer (NSCLC): can patient stratification be improved in the UK Tayside population? A retrospective cohort study. [2023]

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

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. [2022]