A Study of PRT1419 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This is a Phase 1 dose-escalation study of PRT1419, a myeloid cell leukemia 1 (MCL1) inhibitor, in patients with advanced solid tumors. The purpose of this study is to define the dosing schedule, maximally tolerated dose and/or estimate the optimal biological dose to be used in subsequent development of PRT1419.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
This is a multicenter, open-label, dose-escalation Phase 1 study of PRT1419, a MCL1 inhibitor, evaluating patients with relapsed or refractory solid tumors, including breast, lung, sarcoma and melanoma as part of a 28-day treatment cycle. The study will employ a "3+3" dose escalation design. The dose may be escalated until a dose limiting toxicity is identified.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: PRT1419 PRT1419 will be administered by intravenous infusion |
Drug: PRT1419
PRT1419 will be administered by intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- Dose limiting toxicities (DLT) of PRT1419 [Baseline through Day 28]
Dose limiting toxicities will be evaluated through the first cycle
- Maximally tolerated dose (MTD) and/or optimal biological dose (OBD) [Baseline through approximately 2 years]
The MTD and/or OBD will be established for further investigation in participants with advanced solid tumors.
- Recommended phase 2 dose (RP2D) and schedule of PRT1419 [Baseline through approximately 2 years]
The RP2D will be established for further investigation in participants with advanced solid tumors.
Secondary Outcome Measures
- Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments [Baseline through approximately 2 years]
Safety and tolerability will be assessed by recording adverse events (AEs) and serious adverse events (SAEs) according to Common Terminology Criteria for Adverse Events (CTCAE)
- Pharmacokinetic profile of PRT1419: maximum observed plasma concentration [Baseline through approximately 2 years]
PRT1419 pharmacokinetics will be calculated including the maximum observed plasma concentration
- Anti-tumor activity of PRT1419: measurement of objective responses [Baseline through approximately 2 years]
Anti-tumor activity of PRT1419 will be based on the measurement of objective responses
- Progression-free survival [Baseline through approximately 2 years]
Progression-free survival will be calculated from the first administration of PRT1419 until death or until the criteria for disease progression are met
Eligibility Criteria
Criteria
Inclusion Criteria:
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Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
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Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
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Left ventricular ejection fraction of ≥ 50%
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Female patients of childbearing potential must have a negative pregnancy test within 7 days of the start of treatment and must agree to use a highly effective method of contraception during the trial
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Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ Grade 1)
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All patients on prior investigational agents must wait at least 5 half-lives of the agent in question, or 28 days, whichever is longer before study entry
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Most recent lab values meet the following criteria:
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Absolute neutrophil count > 1.0 x 10^3/μL;
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Platelet count > 75,000/μL;
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Hemoglobin > 9.0 g/dL
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Histologically confirmed advanced or metastatic solid tumor indicated below that is relapsed, refractory, or intolerant to available therapies with known benefit:
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Sarcoma not amendable to curative treatment with surgery or radiotherapy;
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Melanoma (non-resectable or metastatic);
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Small cell lung cancer (extensive-stage);
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Non-small cell lung cancer;
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Triple negative breast cancer (histopathologically or cytologically confirmed).
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Esophageal cancer
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Cervical cancer
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Head and neck cancer
Exclusion Criteria:
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Known hypersensitivity to any of the components of PRT1419
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Primary malignancies of the CNS, or uncontrolled CNS metastases, including impending spinal cord compression
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Female patients who are pregnant or lactating
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Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
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Mean QTcF interval of >480 msec
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History of heart failure, additional risk factors for arrhythmias or requiring concomitant medications that prolong the QT/QTc interval
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HIV positive; known active hepatitis B or C
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Uncontrolled intercurrent illnesses
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Treatment with strong inhibitors of CYP2C8
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Prior exposure to an MCL1 inhibitor
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History of another malignancy except:
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Malignancy treated with curative intent with no known active disease for >2 years at study entry;
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Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
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Adequately treated carcinoma in situ without evidence of disease;
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Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Sarah Cannon Research Institute at HealthONE | Denver | Colorado | United States | 80218 |
2 | Florida Cancer Specialists | Lake Mary | Florida | United States | 32746 |
3 | Florida Cancer Specialists | Sarasota | Florida | United States | 34232 |
4 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
5 | Thomas Jefferson University, Sidney Kimmel Cancer Center | Philadelphia | Pennsylvania | United States | 19107 |
6 | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
7 | Tennessee Oncology | Nashville | Tennessee | United States | 37203 |
Sponsors and Collaborators
- Prelude Therapeutics
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRT1419-02