PRT3789 + Pembrolizumab for Solid Tumors

Not currently recruiting at 8 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: PRT3789 (an experimental treatment) and pembrolizumab (also known as KEYTRUDA, an immunotherapy drug), to evaluate their safety and effectiveness against certain advanced cancers. It specifically targets solid tumors with a SMARCA4 mutation. The trial seeks participants whose cancer has either returned or spread and who can no longer use standard treatments. Participants must have a confirmed SMARCA4 mutation in their tumor and show cancer progression despite previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that pembrolizumab, one of the treatments in this trial, has been used safely in many patients for various conditions. Most people tolerate it well, though some might experience fatigue or nausea.

Regarding PRT3789, this study is in the early testing phase, so its safety is still under evaluation. In studies like this, researchers closely monitor for any side effects to ensure participant safety. The goal of combining PRT3789 with pembrolizumab is to enhance effectiveness while maintaining a focus on safety.

Overall, while pembrolizumab has a proven safety record, the safety of PRT3789 is still being assessed. Participants in this trial will be closely monitored to manage any side effects promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of PRT3789 and Pembrolizumab for treating solid tumors because this approach offers a new way to tackle these cancers. Pembrolizumab is already known for its ability to unleash the immune system against cancer cells, but PRT3789 is the standout here, as it is a novel compound with a unique mechanism of action that could enhance this immune response. Unlike standard treatments that often rely solely on enhancing immune checkpoint inhibition, this combination aims to provide a more comprehensive attack on cancer cells, potentially leading to better outcomes for patients. The innovative delivery method of PRT3789, administered weekly alongside Pembrolizumab every three weeks, could also improve convenience and effectiveness compared to current treatments.

What evidence suggests that this trial's treatments could be effective for solid tumors with a SMARCA4 mutation?

Research has shown that pembrolizumab, a drug approved for treating several cancers, can help the immune system identify and attack cancer cells. This is particularly beneficial for solid tumors with specific mutations, such as SMARCA4. In this trial, participants will receive a combination of PRT3789 and pembrolizumab. PRT3789 is a new treatment designed to directly target these mutations and is being studied for its effectiveness alongside pembrolizumab. Early results suggest that combining PRT3789 with pembrolizumab may enhance the treatment's effectiveness against these advanced tumors. Although further research is necessary, this combination therapy is being explored for its potential to improve outcomes for patients with these challenging-to-treat cancers. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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, 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]

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 (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]

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]

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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06682806

NCT06682806 | A Study of PRT3789 in Combination With ... A Phase 2, Safety and Efficacy Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors With a SMARCA4 Mutation.

2. preludetx.com preludetx.com/a-phase-2-safety-and-efficacy-study-of-prt3789-in-combination-with-pembrolizumab-in-patients-with-advanced-or-metastatic-solid-tumors-and-a-smarca4-mutation/

A Phase 2 Safety and Efficacy Study of PRT3789 in ... A Phase 2 Safety and Efficacy Study of PRT3789 in Combination With Pembrolizumab in Patients With Advanced or Metastatic Solid Tumors and a SMARCA4 Mutation.

3. asco.org asco.org/abstracts-presentations/ABSTRACT504210

A phase 2 safety and efficacy study of PRT3789 in ... A phase 2 safety and efficacy study of PRT3789 in combination with pembrolizumab in patients with advanced or metastatic solid tumors and a SMARCA4 mutation.

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/prelude-therapeutics-merck-prt3789-keytruda

Prelude Therapeutics Collaborates With Merck to Evaluate ... The clearance allowed Prelude to proceed with a Phase I study ( NCT05639751 ) of PRT3789 in patients with advanced solid tumors in a biomarker ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6527794/

Clinical utility of pembrolizumab in the management of ... We review here the current indications of this drug, the main prognostic and predictive factors of its efficacy as well as the potential forthcoming indications ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40157574/

the phase III 3475A-D77 trial Overall exposure and trough concentrations of pembrolizumab s.c. 790 mg q6w were noninferior to those of pembrolizumab i.v. 400 mg q6w given with ...

7. clinicaltrialsarena.com clinicaltrialsarena.com/news/prelude-trial-prt3789-keytruda/

Prelude and MSD partner to trial PRT3789 and KEYTRUDA The study's objectives include establishing the tolerability and safety profile of PRT3789, evaluating its activity, pharmacokinetics, and ...