An Initial Safety Study of Gedatolisib Plus PTK7-ADC for Metastatic Triple-negative Breast Cancer

Study Overview
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Brief Summary
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Phase 1 study to evaluate the safety and effect of Gedatolisib and PTK7-ADC for the treatment of triple negative breast cancer

Official Title
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An Initial Safety Study of Gedatolisib Plus PTK7-ADC for Metastatic Triple-negative Breast Cancer

Conditions
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Triple Negative Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Gedatolisib
* Drug: PTK7-ADC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic Triple-negative Breast Cancer Willingness to undergo tumor biopsy Patients must have received at least 1 prior chemotherapy regimen for metastatic disease Exclusion Criteria: Previous treatment with mTOR inhibitor Untreated brain metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Study will enroll 3 patients to the cohort 1 dose level. If 0 of 3 patients experience a DLT, the study will proceed to cohort 2. If 1 patient experiences a DLT, 3 additional patients will be enrolled into cohort 1. If 1 of 6 patients experience a DLT, the study will proceed and 3 patients will be enrolled to the cohort 2 dose level. If 0 patients experience a DLT in cohort 2, the study will proceed to cohort 3. If 1 patient experiences a DLT at cohort 2, 3 additional patients will be enrolled into cohort 2. If the study proceeds to cohort 3, 3 patients will be enrolled at this dose level. If 0 patients experience a DLT, the study will enroll an additional 3 patients at the cohort 3 dose level to better define the safety profile. If 1 of 3 patients experiences a DLT at cohort 3, 3 additional patients will still be enrolled into cohort 3. If 1 of 6 patients experience a DLT, the study will complete.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gedatolisb + PTK7-ADC<br> | Drug: Gedatolisib<br>* Gedatolisb will be intravenously administered on Day 1, Day 8 and Day 15 of every 21 day cycle at a dose of 110 mg or 180mg depending on cohort assignment.<br>Drug: PTK7-ADC<br>* PTK7-ADC will be administered on Day 1 of every 21 day cycle at a dose of 1.4mg/kg or 2.8 mg/kg depending on cohort assignment.<br>* Other names: PF-06647020;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Gedatolisb + PTK7-ADC using NCI CTCAE v4.0 | safety and toxicity data will be assessed using NCI CTCAE v4.0 and tabulated and reported | through study completion i.e. up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy in all enrolled subjects | efficacy as determined by clinical benefit at 18 weeks | 18 weeks | 
| Overall response rate in all enrolled subjects | efficacy as determined by overall response rate | through study completion i.e. up to 1 year | 
| Progression free survival in all enrolled subjects | efficacy as determined by progression free survival | through study completion i.e. up to 1 year | 
| Pharmacodynamic determination of inhibition of PI3k signaling | Pathological H-score will be determined from tissue obtained at screening and Cycle 1 Day 15. H-score will be compared to calculate percentage inhibition between samples. | Cycle 1 Day 15 | 
| Pharmacodynamic determination modulation of Wnt pathway | pathological H-score will be determined from tissue obtained at screening and Cycle 1 Day 15. H-score will be compared to calculate percentage change in expression between samples. | Cycle 1 Day 15 | 
| Pharmacodynamic determination modulation of Wnt pathway | RNA sequencing of tissue collected at screening and Cycle 1 Day 1 to compare Wnt pathway expression after treatment | Cycle 1 Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer