A Study Of PF-06263507 In Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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To assess the safety and tolerability at increasing dose levels of PF-06263507 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Official Title
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A PHASE 1, DOSE ESCALATION STUDY OF PF-06263507 IN PATIENTS WITH ADVANCED SOLID TUMORS

Conditions
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Neoplasms, Carcinoma, Non Small Cell Lung, Breast Neoplasms, Ovarian Neoplasms

Intervention / Treatment
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* Drug: PF-06263507
* Drug: PF-06263507


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for which no standard therapy is available. Performance Status of 0 or 1. Adequate bone marrow, kidney, liver, and heart function. Exclusion Criteria: Brain metastases requiring steroids. Major surgery or anti-cancer therapy within 4 weeks of study treatment start. Active bacterial, fungal or viral infection.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br> | Drug: PF-06263507<br>* Part 1 - PF-06263507 will be administered intravenously in 21-day cycles in cohorts of 2 or more patients starting at a dose of 0.05 mg/kg. Increases in dose will continue until MTD is determined.<br>Drug: PF-06263507<br>* Part 2 - Patients with select tumor types will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose-limiting Toxicities (DLT) | DLT was defined as any of the following adverse events (AEs) occurring in the first cycle of treatment (21 days) which were attributable to PF-06263507: 1) Grade 4 neutropenia lasting >7 days, 2) Febrile neutropenia, 3) Grade >=3 neutropenia with infection, 4) Any grade thrombocytopenia associated with clinically significant or life-threatening bleeding, 4) Grade 4 thrombocytopenia, 5) Any grade >=3 non-hematologic toxicities, 6) A positive cardiac troponin I result, 7) Persisting non-hematologic toxicities resulted in more than 2 weeks delay in receiving the next scheduled cycle. Severity of AEs was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Baseline up to Cycle 2 Day 1 (22 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), by Maximum National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade was reported. | Baseline, Day 1 to 15 for Cycle 1, Day 1 to end of treatment for Cycle 2 and subsequent cycles, and follow-up. | 
| Number of Participants With Treatment-related AEs, by Maximum NCI CTCAE (Version 4.0) Grade | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade was reported. | Baseline, Day 1 to 15 for Cycle 1, Day 1 to end of treatment for Cycle 2 and subsequent cycles, and follow-up. | 
| Number of Participants With Hematological Test Abnormalities in All Cycles. | Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 hematological test abnormalities. | Baseline, Days 1, 3, 8 and 15 for Cycle 1, Days 1, 8, 15 for Cycle 2 and subsequent cycles, and end of treatment | 
| Number of Participants With Chemistry Test Abnormalities in All Cycles. | Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 chemistry tests abnormalities. | Baseline, Days 1, 3, 8 and 15 for Cycle 1, Days 1, 8, 15 for Cycle 2 and subsequent cycles, and end of treatment | 
| Number of Participants With Abnormalities in Urine Protein in All Cycles. | Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 abnormalities in urine protein. | Baseline, Day 15 for Cycle 1, Day 1 for Cycle 2 and subsequent cycles, and end of treatment | 
| Number of Participants With Change From Baseline and Absolute Values in Vital Signs Meeting Categorical Summarization Criteria | Criteria for potentially clinically important (PCI) change in vital signs included: sitting systolic blood pressure (SBP) of <90 millimeters of mercury (mm Hg) or change in sitting SBP of >=30 mm Hg, sitting diastolic blood pressure (DBP) of <50 mm Hg or change in sitting DBP of >=20 mm Hg, sitting pulse rate of <40 or >120 beats per minute (bpm). | Baseline, Days 1, 3, 8 and 15 for Cycle 1, Days 1, 8, 15 for Cycle 2 and subsequent cycles, end of treatment, and follow-up. | 
| Number of Participants With Positive Anti-PF-06263507 Antibody | The number of participants with positive anti-PF-06263507 antibody. | Pre-dose Day 1, Cycle 1 Day 15, Day 1 of every Cycle, up to 21 days after the last dose of study medication | 
| Number of Participants With Best Overall Response (BOR) | Number of participants with best overall response. Complete response (CR)=disappearance of all target lesions. Partial Response (PR)>=30% decrease in sum of longest dimensions of lesions taking as reference baseline sum longest dimensions. Progressive disease (PD) >=20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of the longest dimensions since treatment start, or the appearance of >=1 new lesion. Stable disease (SD)=neither shrinkage for PR or increase for PD taking as reference smallest sum of longest dimensions since treatment start. | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months. | 
| Objective Response | Number of particpants with objective response: confirmed CR or confirmed PR according to RECIST. CR was defined as the disappearance of all target lesions. A PR was defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors had to have been confirmed by repeat studies that were performed ≥ 4 weeks after the criteria for response were first met. | Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months. | 
| Overall Survival | Overall survival was defined as the time from initial dose until death from any cause, and was measured in the intent-to-treat population. | Baseline to death | 
| Time to Reach Maximum Observed Serum PF-06263507 Concentration (Tmax) |  | Baseline,Cycle 1 Day 1 pre-dose,1,4,8,12,24, and 48 hrs post dose,Day 5,Day 8 and Day 15;Day 1 of Cycle 2 and 3,Day 1 of Cycle 4 pre-dose,1,8,12,24 hr post dose, Day 8 and Day 15,every cycle thereafter on day 1 pre-dose, and up to 21 days after last dose. | 
| Time to Reach Maximum Observed Serum PF-06281192 Concentration (Tmax) |  | Baseline,Cycle 1 Day 1 pre-dose,1,4,8,12,24, and 48 hrs post dose,Day 5,Day 8 and Day 15;Day 1 of Cycle 2 and 3,Day 1 of Cycle 4 pre-dose,1,8,12,24 hr post dose, Day 8 and Day 15,every cycle thereafter on day 1 pre-dose, and up to 21 days after last dose. | 
| Time to Reach Maximum Observed Serum PF-06264490 Concentration (Tmax) |  | Baseline,Cycle 1 Day 1 pre-dose,1,4,8,12,24, and 48 hrs post dose,Day 5,Day 8 and Day 15;Day 1 of Cycle 2 and 3,Day 1 of Cycle 4 pre-dose,1,8,12,24 hr post dose, Day 8 and Day 15,every cycle thereafter on day 1 pre-dose, and up to 21 days after last dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, ADC 5T4, PF-06263507, solid tumors, lung cancer, breast cancer, ovarian cancer, tumors, neoplasm metastasis