A Study of PF-06873600 in People With Cancer

Study Overview
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Brief Summary
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The purpose of this clinical trial is to learn about the safety and effects of study medicine (PF-06873600) when taken alone or with hormone therapy by people with cancer. People may be able to participate in this study if they have the following types of cancer: Hormone Receptor positive (HR+) breast cancer; Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer that is advanced or metastatic (spread to other parts of the body); triple negative breast cancer; epithelial ovarian cancer; fallopian tube cancer; or primary peritoneal cancer. All participants in this study will receive the study medicine by mouth, 1 to 2 times a day at home. The dose of the study medicine may be changed during the study. Some participants will also receive hormone therapy. The hormone therapy will be either letrozole by mouth once a day at home, or fulvestrant as a shot into the muscle. Fulvestrant will be given every two weeks at the study clinic for the first month, and then once a month after that. Participants will take part in this study for at least 7 to 8 months, depending on how they respond to the therapy. During this time participants will visit the study clinic once a week.

Detailed Description
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This is a Phase 1/2a, open-label, multi-center, non-randomized, multiple dose, safety, tolerability, pharmacokinetic, and pharmacodynamic study of PF-06873600 administered as a single agent in sequential dose levels and then in combination with endocrine therapy. In Part 1A and Part 1C, successive cohorts of patients will receive escalating doses of PF-06873600 and then in dose finding (Part 1B) with PF-06873600 in combination with endocrine therapy (ET). This study contains 2 parts, dose escalation with single agent (Part 1A and 1C) and then dose finding with PF-06873600 in combination with endocrine therapy (Part 1B) followed by dose expansion arms of PF-06873600 in combination with endocrine therapy (Part 2).

Official Title
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PHASE 1/2A DOSE ESCALATION AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETIC, PHARMACODYNAMICS AND ANTI-TUMOR ACTIVITY OF PF-06873600 AS A SINGLE AGENT AND IN COMBINATION WITH ENDOCRINE THERAPY

Conditions
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HR+ HER2- Metastatic Breast Cancer, Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer, Triple Negative Breast Cancer, Male Breast Cancer

Intervention / Treatment
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* Drug: PF-06873600
* Drug: Endocrine Therapy 1
* Drug: Endocrine Therapy 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer • Prior combined CDK 4/6 inhibitor and endocrine therapy and 1 or 2 prior lines of chemotherapy Have a diagnosis of metastatic triple negative breast cancer (TNBC) • Up to 1-2 prior lines of chemotherapy Have a diagnosis of advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) • Up to 2-3 prior lines of therapy Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 Measurable disease or non-measurable disease and refractory to or intolerant of existing therapies (Part 1) Measurable disease as defined by RECIST 1.1 is required (Part 1B and Part 2 only) Exclusion Criteria: Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ Major surgery or radiation within 4 weeks prior to study entry Last anti-cancer treatment within 2 weeks prior to study entry Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry Pregnant or breastfeeding female patients Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastro intestinal function or GI disease

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Single Agent Dose Escalation | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>|
| Experimental: Dose Finding Endocrine Therapy 1 Combination<br>Part 1B PF-06873600 plus Endocrine Therapy 1 | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>Drug: Endocrine Therapy 1<br>* Endocrine Therapy 1<br>|
| Experimental: Dose Finding Endocrine Therapy 2 Combination<br>Part 1B PF-06873600 plus Endocrine Therapy 2 | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>Drug: Endocrine Therapy 2<br>* Endocrine Therapy 2<br>|
| Experimental: Dose Expansion Arm A<br>PF-06873600 as a Single Agent | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>|
| Experimental: Dose Expansion Arm B<br>PF-06873600 as a Single Agent in Various Tumor Types | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>|
| Experimental: Dose Expansion Arm C<br>PF-06873600 in Combination with Endocrine Therapy 1 | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>Drug: Endocrine Therapy 1<br>* Endocrine Therapy 1<br>|
| Experimental: Dose Expansion Arm D<br>PF-06873600 in Combination with Endocrine Therapy 1 | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>Drug: Endocrine Therapy 1<br>* Endocrine Therapy 1<br>|
| Experimental: Dose Expansion Arm E<br>PF-06873600 in Combination with Endocrine Therapy 2 | Drug: PF-06873600<br>* PF-06873600 tablet for oral dosing<br>Drug: Endocrine Therapy 2<br>* Endocrine Therapy 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with dose limiting toxicities in the Dose Escalation portion |  | up to 28 days | 
| Safety and Tolerability as assessed by adverse event monitoring for patients enrolled in the Dose Escalation, Dose Finding and Dose Expansion Arms | Adverse events | Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months | 
| Safety and Tolerability as assessed through monitoring of hematology and blood chemistry laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms | safety laboratory abnormalities | Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months | 
| Safety and Tolerability as assessed through vital sign monitoring for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms | vital signs | Weekly during Cycle 1 (each cycle is 28 days) and 2 and then every 28 days through study completion, up to approximately 24 months | 
| Safety and Tolerability as assessed by heart rate corrected QT interval for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms | heart rate corrected QT interval | Day 1, 8 and 15 of Cycle 1 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months | 
| Objective Response Rate (ORR) observed in patients in the Dose Expansion Arms | Number of patients in each Arm. ORR (number of patients with a Partial Response (PR) + Complete Response (CR) relative to the number of evaluable patients | baseline up to approximately 24 months | 
| Safety and Tolerability as assessed through monitoring of coagulation laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms | safety laboratory abnormalities | Day 1 of Cycle 1 (each cycle is 28 days) and 2 and at completion, approximately 24 months | 
| Safety and Tolerability as assessed through monitoring of urinalysis laboratory assessments for patients enrolled in the Dose Escalation, Dose Finding Portion and the Dose Expansion Arms | safety laboratory abnormalities | Screening and at completion, approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Single Dose: Plasma concentrations with and without food observed in patients enrolled in one of the single agent Dose Expansion Arms |  | 7 days prior to Cycle 1 (each cycle is 28 days) and in Cycle 1 (each cycle is 28 days) | 
| Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Single Dose: Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Single Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion and Dose Expansion Arms | Pharmacokinetic (PK) assessments for PF-06873600 | Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months | 
| Tumor Response observed in patients in Dose Escalation and Dose Finding portion |  | baseline up to approximately 24 months | 
| Duration of Response (DOR) in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |  | baseline up to approximately 24 months | 
| Progression Free Survival (PFS) observed in patients in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |  | baseline up to approximately 24 months | 
| Time to Progression (TTP) observed in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |  | baseline up to approximately 24 months | 
| Overall Survival observed in patients enrolled in the Dose Expansion Arms |  | baseline up to approximately 24 months | 
| Pharmacodynamic (PD) biomarkers (pRb and Ki67) in tumor tissue in patients enrolled in the Dose Escalation and Dose Finding portion and Dose Expansion Arms |  | Screening, Cycle 1 (each cycle is 28 days), Cycle 2 and 3 and at the study completion visit, up to approximately 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone Receptor (HR) Positive Breast Cancer, Estrogen receptor (ER) positive, Progesterone receptor (PR) positive, Cyclin-dependent kinase (CDK), Human epidermal growth factor receptor 2 (HER2) negative, Advanced breast cancer, Metastatic breast cancer (MBC), Triple negative breast cancer (TNBC), Epithelial ovarian cancer (EOC), Fallopian tube cancer, Primary peritoneal cancer (PPC), CDK4/6 inhibitor, Endocrine Therapy (ET), Measurable disease, Luteinizing Hormone Releasing Hormone (LHRH) Agonist, Goserelin, Leuprolide acetate