PRT7732 for Solid Tumors

Recruiting at 21 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

104 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1 study to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PRT7732 in patients with select advanced or metastatic solid tumors with a SMARCA4 mutation.

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.

What makes the drug PRT7732 unique for treating solid tumors?

PRT7732 is unique because it may involve targeting the p73 protein, which plays a role in tumor growth and response to cancer treatments. This approach could offer a novel mechanism compared to existing therapies for solid tumors. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Willing to provide either archival or fresh tumor tissue sample

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

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

Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy. [2020]

2. United States 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. [2020]

3. England pubmed.ncbi.nlm.nih.gov

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

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

An Exceptionally Potent Inhibitor of Human CD73. [2020]

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

p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. [2022]