PRT7732 for Solid Tumors
Recruiting in Palo Alto (17 mi)
+17 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Prelude Therapeutics
Must not be taking: Targeted therapy
Disqualifiers: Cardiac disease, CNS metastases, others
No Placebo Group
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.
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
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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.
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Trial 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 (SMARCA2 Degrader)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: PRT7732Experimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The University of Texas MD Anderson Cancer CenterHouston, TX
University Hospitals Cleveland Medical CenterCleveland, OH
Memorial Sloan Kettering Cancer Center - Main CampusNew York, NY
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Prelude TherapeuticsLead Sponsor
References
Expression of the p73 protein in rectal cancers with or without preoperative radiotherapy. [2020]To investigate p73 expression in normal mucosa, primary tumor, and metastasis in relation to radiotherapy (RT) response and clinicopathologic/biologic variables in rectal cancers.
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]The role of the recently identified first p53-homologue, p73, in neoplastic transformation is unknown. To elucidate p73 gene expression in hematopoiesis, we investigated samples from chronic myeloid leukemia (CML) and acute myeloid leukemia patients, leukemia cell lines, as well as mature and immature normal hematopoietic cells by real-time quantitative RT-PCR and Western blot analysis. We found a distinct p73 expression profile with highest p73 mRNA transcript levels in hematopoietic malignancies such as CML blast crisis and acute myelogenous leukemia versus CML chronic phase and normal controls. Mono- and biallelic p73 expression was found in both normal and malignant hematopoiesis. p73 protein was expressed at various levels in leukemia samples and cell lines but could not be detected in any normal controls tested. Our results point to a distinct yet undefined role of p73 in the pathogenesis of myeloid neoplasms.
Aberrant expression of DeltaNp73 in benign and malignant tumours of the prostate: correlation with Gleason score. [2018]The p73 gene is a p53 homologue that induces apoptosis and inhibits cell proliferation. N-terminal truncated isoforms of p73 (DeltaNp73) act as dominant-negative inhibitors of wild-type p53 and TAp73 and result in tumour growth in nude mice.
An Exceptionally Potent Inhibitor of Human CD73. [2020]We recently reported the initiation of a Phase I clinical trial with AB680, a potent human CD73 inhibitor, being developed for the treatment of solid tumors (NCT03677973). We undertook a detailed kinetic analysis of the interaction between human CD73 and AB680 to determine the mode of inhibition. We found AB680 to be a reversible, slow-onset competitive inhibitor of human CD73 with a Ki of 5 pM. Clinical candidates of this potency are uncommon and deserve special consideration during lead optimization.
p53 polymorphism influences response in cancer chemotherapy via modulation of p73-dependent apoptosis. [2022]Intact p73 function is shown to be an important determinant of cellular sensitivity to anticancer agents. Inhibition of p73 function by dominant-negative proteins or by mutant p53 abrogates apoptosis and cytotoxicity induced by these agents. A polymorphism encoding either arginine (72R) or proline (72P) at codon 72 of p53 influences inhibition of p73 by a range of p53 mutants identified in squamous cancers. Clinical response following cisplatin-based chemo-radiotherapy for advanced head and neck cancer is influenced by this polymorphism, cancers expressing 72R mutants having lower response rates than those expressing 72P mutants. Polymorphism in p53 may influence individual responsiveness to cancer therapy.