PRT7732 for Solid Tumors

Not currently recruiting at 32 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Prelude Therapeutics

Must not be taking: Targeted therapy

Disqualifiers: Cardiac disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and early effects of a new treatment, PRT7732, for individuals with advanced solid tumors that have a specific genetic change known as a SMARCA4 mutation. The researchers aim to assess patient tolerance to this oral medication and understand its behavior in the body. Individuals with solid tumors that have spread or recurred after other treatments, and who have this mutation, might be suitable for this trial. Participants should be willing to adhere to the trial schedule and provide a tumor sample. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on any targeted therapy directed against BRM/BRG1 (SMARCA2/SMARCA4), you may not be eligible to participate.

Is there any evidence suggesting that PRT7732 is likely to be safe for humans?

Research shows that PRT7732 remains in the early stages of testing, so detailed safety information is limited. In these initial studies, the main goal is to find a safe dose for patients with advanced solid tumors. Researchers closely monitor for any side effects as they adjust the doses. Since this marks the first time PRT7732 is tested in humans, information about how well people tolerate it or what side effects might occur is still scarce. This phase is crucial to ensure the treatment can be safely administered to more people in future studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

PRT7732 is unique because it's an oral capsule targeting solid tumors, offering a more convenient treatment method compared to intravenous therapies. Researchers are excited because PRT7732 uses a novel approach for dose escalation guided by the BLRM method, which helps in finding the right dose more efficiently. This could potentially enhance patient outcomes by optimizing the dosage specific to individual needs.

What evidence suggests that PRT7732 might be an effective treatment for solid tumors?

Research shows that PRT7732 targets tumors with a specific genetic change called a SMARCA4 mutation, which can promote cancer growth. PRT7732 aims to break down a protein called SMARCA2, linked to this growth. Early studies suggest that targeting SMARCA2 might slow or stop the spread of cancer cells. Although human studies provide limited information, this method has shown promise in lab tests and animal studies. The trial aims to determine if PRT7732 can effectively shrink tumors or halt their growth in patients with these specific genetic changes. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for people with advanced or metastatic solid tumors that have a specific genetic change called a SMARCA4 mutation. It's open to those who meet certain health conditions and haven't had success with other treatments.

Inclusion Criteria

Must have measurable or non-measurable (but evaluable) disease per RECIST v1.1

Willing to provide either archival or fresh tumor tissue sample

My blood, kidney, and liver functions are all within normal ranges.

Exclusion Criteria

My solid tumor has a SMARCA2 mutation or lacks SMARCA2 protein.

I haven't had any cancer except for certain skin cancers or other low-risk types in the past 3 years.

I do not have uncontrolled heart, electrolyte, or severe brain/spinal cord conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PRT7732 as an oral capsule once daily with dose escalation/de-escalation guided by the BLRM method until the recommended dose for expansion (RDE) is determined

Up to 2 years

Dose Escalation

Dose escalation phase to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLTs)

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PRT7732

Trial Overview The study is testing PRT7732, an oral medication designed to target the SMARCA2 protein in patients. This early-phase trial will assess how safe it is, what doses are tolerable, how the body processes it, and if it works against cancer.

How Is the Trial Designed?

Group I: PRT7732 Experimental Treatment 1 Intervention

PRT7732 is administered as an oral capsule once daily. Dose escalation/de-escalation decisions will be guided by the BLRM method until the RDE is determined.

Who Is Running the Clinical Trial?

Prelude Therapeutics

Lead Sponsor

Trials

11

Recruited

910+

Published Research Related to This Trial

In rectal cancer patients, p73 expression was significantly higher in primary tumors compared to normal mucosa, indicating its potential role in tumor biology and response to treatment.

Patients with p73-negative tumors showed a tendency for lower local recurrence rates after radiotherapy, suggesting that p73 status could be a useful biomarker for predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy. Pfeifer, D., Gao, J., Adell, G., et al.[2020]

DeltaNp73 is significantly overexpressed in prostate cancer tissues compared to normal samples, indicating its potential role in the progression of the disease.

The expression of DeltaNp73 correlates with the Gleason score in prostate carcinomas, suggesting that it may be linked to tumor aggressiveness and could serve as a biomarker for cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aberrant expression of DeltaNp73 in benign and malignant tumours of the prostate: correlation with Gleason score. Guan, M., Chen, Y.[2018]

AB680 is a potent human CD73 inhibitor currently undergoing a Phase I clinical trial for solid tumors, demonstrating a promising approach in cancer treatment.

The drug acts as a reversible, slow-onset competitive inhibitor of CD73, with a very low inhibition constant (Ki) of 5 pM, indicating its strong binding affinity and potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Exceptionally Potent Inhibitor of Human CD73. Bowman, CE., da Silva, RG., Pham, A., et al.[2020]

The function of p73 is crucial for how sensitive cancer cells are to anticancer treatments, as its inhibition by mutant p53 can prevent cell death from these therapies.

A specific genetic variation in p53 (either arginine or proline at codon 72) affects the effectiveness of cisplatin-based chemotherapy in advanced head and neck cancer, with 72R variants showing lower response rates compared to 72P variants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. Bergamaschi, D., Gasco, M., Hiller, L., et al.[2022]

In patients with chronic myeloid leukemia (CML) and acute myeloid leukemia, p73 gene expression was significantly higher compared to normal hematopoietic cells, suggesting a potential role in the development of these blood cancers.

The study found that p73 protein was present in leukemia samples but absent in normal controls, indicating that p73 may play a distinct and undefined role in the pathogenesis of myeloid neoplasms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinct expression patterns of the p53-homologue p73 in malignant and normal hematopoiesis assessed by a novel real-time reverse transcription-polymerase chain reaction assay and protein analysis. Peters, UR., Tschan, MP., Kreuzer, KA., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06560645

NCT06560645 | A Study of PRT7732, an Oral SMARCA2 ... This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select ...

2. preludetx.com preludetx.com/clinical-trials/prt7732-trials/

PRT7732 Trials This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select ...

3. clinicaltrial.be clinicaltrial.be/en/details/447209?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study of PRT7732, an Oral SMARCA2 Degrader, in ... Primary outcomes 6 · Dose Limiting toxicity (DLT) of PRT7732 · Safety and tolerability of PRT7732 as measured by incidence of DLTs · Safety and tolerability of ...

4. mskcc.org mskcc.org/cancer-care/clinical-trials/24-379

A Phase 1 Study of PRT7732 in People With Solid Tumors The purpose of this study is to find the best dose of PRT7732 that can be given safely in people with advanced solid tumors.

5. clinrol.com clinrol.com/study/NCT06560645

PRT7732 in Advanced Solid Tumors With SMARCA4 ... Phase 1 study assessing the safety and efficacy of PRT7732, an oral SMARCA degrader, in patients with advanced solid tumors and SMARCA4 mutations.