Clinical trial NCT05538572: A Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors
Official title: A Phase 1 Open-Label, Multi-Center, Safety and Efficacy Study of PRT3645 in Participants With Select Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Glioblastoma
Head and Neck Squamous Cell Carcinoma
Malignant Mesothelioma
Non-small Cell Lung Cancers
Sarcoma
Endometrial Cancer
Keywords: Advanced Solid Tumors
Breast Cancer
CDK4/6
Cyclin-dependent Kinase 4
Cyclin-dependent Kinase 6
Glioblastoma
Head and Neck Squamous Cell Carcinoma
HNSCC
Malignant Mesothelioma
Metastatic Solid Tumors
Non-small Cell Lung Cancers
NSCLC
PRT3645
Sarcoma
Endometrial Cancer
Lead sponsor: Prelude Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-09-14
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 dose-escalation study of PRT3645, a Cyclin-dependent Kinase 4/6 (CDK4/6) inhibitor, in patients with advanced or metastatic solid tumors. The purpose of this study is to investigate the safety, tolerability, dose limiting toxicity, and to determine maximally tolerated dose and recommended phase 2 dose to be used in subsequent development of PRT3645.

Detailed description: This is an open-label, multicenter, dose-escalation Phase 1 study of PRT3645, a CDK4/6 inhibitor, evaluating patients with selected advanced or metastatic solid tumors including breast cancer (BC), glioblastoma (GBM), non-small cell lung cancer (NSCLC), sarcomas, head and neck squamous cell carcinoma (HNSCC), malignant mesothelioma, and endometrial cancer. The study plan expects to evaluate approximately eight dose levels however additional dose levels may be explored. Taking into account pharmacokinetic and pharmacodynamic data from the preceding dose levels, the dose may be escalated until a dose limiting toxicity is identified. Up to 15 patients may be enrolled at a dose shown to be tolerated for confirmation of the MTD and/or RP2D.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed advanced, recurrent, or metastatic solid tumor malignancy that have either progress or ineligible for standard of care therapy:

  1. HR+ and HER2- or HR+ and HER2+ breast cancer
  2. Recurrent GBM (IDH wild type) or CDKN2A/B homozygous deleted IDH-mutant astrocytoma
  3. KRAS-mutant or SMARCA4 loss NSCLC
  4. CDK pathway alternation in any of the following tumor types: malignant mesothelioma, HPV-negative HNSCC (including oral cavity, oropharynx, hypopharynx, and larynx), sarcoma, or NSCLC
  5. Estrogen receptor positive with TP53 wild type endometrial cancer
* Willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
* Must have measurable or non-measureable (but evaluable) disease
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Status (KPS) ≥80% (KPS is for GBM only)
* Adequate organ function.
* Able to swallow and retain oral medication.
* Must provide either archival or fresh tumor tissue sample during screening.

Exclusion Criteria:

* Participants with advanced, symptomatic, extensive visceral disease.
* Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, any upper gastrointestinal surgery including gastric resection, known malabsorption syndrome, or other condition that may impair absorption of PRT3645.
* Treatment with strong inhibitors of CYP3A4.
* History of another malignancy within 3 years except for adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancies, or malignancies previously treated with curative intent and not on active therapy or expected to require treatment or recurrence during the study.
* Clinically significant or uncontrolled cardiac disease, uncontrolled electrolyte disorders, uncontrolled or symptomatic CNS metastases or leptomeningeal disease except for GBM.
* Endometrial cancer patients who had received prior treatment with a CDK 4/6 inhibitor.

Primary outcomes:
measure: Dose limiting toxicity (DLT) of PRT3645
timeFrame: Baseline through Day 28
measure: Safety and tolerability of PRT3645: AEs, CTCAE Assessments
timeFrame: Baseline through approximately 2 years
measure: Maximally tolerated dose (MTD)/Recommended phase 2 dose (RP2D) of PRT3645
timeFrame: Baseline through approximately 2 years
Secondary outcomes:
measure: Efficacy of PRT3645: Tumor assessment and responses
timeFrame: Baseline through approximately 2 years
measure: Pharmacokinetic profile of PRT3645: Minimum and maximum observed plasma concentration
timeFrame: Baseline through approximately 2 years
measure: Pharmacodynamic effect of PRT3645: Target engagement
timeFrame: Baseline through approximately 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Smilow Cancer Hospital Phase 1 Unit
state: Connecticut
city: Celebration
country: United States
facility: AdventHealth Medical Group Oncology Research at Celebration
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center/ NYU Langone Health
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
Study officials:
References: