Clinical trial NCT04837677: A Study of PRT1419 in Patients With Advanced Solid Tumors
Official title: A Phase 1, Open-Label, Multicenter, Dose Escalation Study of PRT1419 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Sarcoma
Melanoma
Lung Cancer
Breast Cancer
Esophageal Cancer
Cervical Cancer
Head and Neck Cancer
Keywords: MCL1
Lead sponsor: Prelude Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-04-08
Enrollment: 26
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 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.

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.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Adequate organ function (bone marrow, hepatic, renal, cardiovascular)
* Left ventricular ejection fraction of ≥ 50%
* 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
* Patients must have recovered from the effects of any prior cancer related therapy, radiotherapy or surgery (toxicity ≤ Grade 1)
* 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
* Most recent lab values meet the following criteria:

  * Absolute neutrophil count \> 1.0 x 10\^3/μL;
  * Platelet count \> 75,000/μL;
  * Hemoglobin \> 9.0 g/dL
* Histologically confirmed advanced or metastatic solid tumor indicated below that is relapsed, refractory, or intolerant to available therapies with known benefit:

  * Sarcoma not amendable to curative treatment with surgery or radiotherapy;
  * Melanoma (non-resectable or metastatic);
  * Small cell lung cancer (extensive-stage);
  * Non-small cell lung cancer;
  * Triple negative breast cancer (histopathologically or cytologically confirmed).
  * Esophageal cancer
  * Cervical cancer
  * Head and neck cancer

Exclusion Criteria:

* Known hypersensitivity to any of the components of PRT1419
* Primary malignancies of the CNS, or uncontrolled CNS metastases, including impending spinal cord compression
* Female patients who are pregnant or lactating
* Inflammatory disorders of the gastrointestinal tract, or subjects with GI malabsorption
* Mean QTcF interval of \>480 msec
* History of heart failure, additional risk factors for arrhythmias or requiring concomitant medications that prolong the QT/QTc interval
* HIV positive; known active hepatitis B or C
* Uncontrolled intercurrent illnesses
* Treatment with strong inhibitors of CYP2C8
* Prior exposure to an MCL1 inhibitor
* History of another malignancy except:

  * Malignancy treated with curative intent with no known active disease for \>2 years at study entry;
  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  * Adequately treated carcinoma in situ without evidence of disease;
  * Other concurrent low-grade malignancies (i.e chronic lymphocytic leukemia (Rai 0)) may be considered after consultation with Sponsor.

Primary outcomes:
measure: Dose limiting toxicities (DLT) of PRT1419
timeFrame: Baseline through Day 28
measure: Maximally tolerated dose (MTD) and/or optimal biological dose (OBD)
timeFrame: Baseline through approximately 2 years
measure: Recommended phase 2 dose (RP2D) and schedule of PRT1419
timeFrame: Baseline through approximately 2 years
Secondary outcomes:
measure: Safety and tolerability of PRT1419: AEs, SAEs, CTCAE assessments
timeFrame: Baseline through approximately 2 years
measure: Pharmacokinetic profile of PRT1419: maximum observed plasma concentration
timeFrame: Baseline through approximately 2 years
measure: Anti-tumor activity of PRT1419: measurement of objective responses
timeFrame: Baseline through approximately 2 years
measure: Progression-free survival
timeFrame: Baseline through approximately 2 years
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Philadelphia
country: United States
facility: Thomas Jefferson University, Sidney Kimmel Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
Study officials:
References: