PRT3789 + Pembrolizumab for Solid Tumors

Recruiting at 5 trial locations

Overseen By Study Contact (Please Do Not Disclose Personal Information)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Prelude Therapeutics

Must not be taking: CYP3A4 inhibitors, St. John's Wort

Disqualifiers: CNS metastases, Pneumonitis, Immunodeficiency, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

If you are currently taking a strong or moderate CYP3A4 inhibitor or inducer, or St. John's Wort, you will need to stop using them at least 15 days before starting the study treatment.

What data supports the effectiveness of the drug pembrolizumab in treating solid tumors?

Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It has been approved for use in advanced melanoma and has demonstrated prolonged tumor response in patients. ^{1 2 3 4 5}

What safety information is available for the treatment PRT3789 + Pembrolizumab?

Pembrolizumab (also known as Keytruda) has been used in various cancer treatments and is generally considered safe, but it can cause side effects. Common side effects include fatigue, cough, nausea, and rash. More serious immune-related side effects can occur, such as inflammation of the lungs (pneumonitis), liver (hepatitis), or thyroid issues, and in rare cases, it can cause type 1 diabetes. ^{1 2 3 6 7}

What makes the drug PRT3789 + Pembrolizumab unique for treating solid tumors?

The combination of PRT3789 and Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells by blocking a pathway that tumors use to hide from immune cells. This combination may offer a novel approach by potentially enhancing the immune response against solid tumors, which could be different from existing treatments that target other pathways or use different mechanisms. ^{1 2 3 6 8}

What is the purpose of this trial?

This is a Phase 2 an open-label, multi-center study to determine the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and anti-tumor activity of PRT3789 in combination with pembrolizumab in patients with advanced, recurrent or metastatic solid tumors with a SMARCA4 mutation.

Eligibility Criteria

This trial is for patients with advanced or metastatic solid tumors, such as esophageal cancer, non-small cell lung cancer, and head and neck cancers that have a SMARCA4 mutation. Specific eligibility details are not provided.

Inclusion Criteria

My condition worsened after standard treatment or I can't receive it.

Patients who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures, including providing informed consent.

My HIV is well-controlled with medication.

Exclusion Criteria

I have been treated with drugs targeting T-cell receptors before.

Pregnant or breastfeeding or plan to become pregnant during the duration of the study.

I have been diagnosed with an immunodeficiency disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Establish the dose of PRT3789 to be used in combination with pembrolizumab

6-8 weeks

Weekly visits for dose administration and monitoring

Main Study (Part 2)

Participants receive PRT3789 and pembrolizumab to evaluate safety, tolerability, and efficacy

2 years

Every 3 weeks for pembrolizumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pembrolizumab
• PRT3789

Trial Overview The study tests PRT3789 combined with pembrolizumab on its safety and effectiveness against certain cancers. It's an open-label Phase 2 trial, meaning both researchers and participants know what treatment is being given.

Participant Groups

Group I: PRT3789/Pembrolizumab combination Experimental Treatment 2 Interventions

PRT3789 is administered as an intravenous infusion once weekly for 3 weeks; Pembrolizumab is administered at 200 mg as an intravenous infusion over 30 min every 3 weeks

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Prelude Therapeutics

Lead Sponsor

Trials

11

Recruited

910+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

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]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

In the phase II KEYNOTE-199 study involving 258 patients with metastatic castration-resistant prostate cancer (mCRPC), pembrolizumab demonstrated modest antitumor activity, with objective response rates of 5% in PD-L1-positive patients and 3% in PD-L1-negative patients, indicating some effectiveness in this challenging population.

The treatment was generally well-tolerated, with 60% of patients experiencing treatment-related adverse events, but only 5% discontinuing due to these events, suggesting that pembrolizumab has an acceptable safety profile while providing encouraging overall survival estimates, particularly in patients with bone-predominant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. Antonarakis, ES., Piulats, JM., Gross-Goupil, M., et al.[2021]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

References

1. 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]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

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

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

Pembrolizumab: first global approval. [2021]

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

Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]