A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Pfizer
- Enrollment
- 60
- Locations
- 10
- Primary Endpoint
- Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1)
Study Overview
Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-06647263 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
Detailed Description
The clinical study will include 2 parts. Part 1 will estimate the MTD in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the RP2D. Part 2 will include patients with previously treated metastatic triple negative breast cancer (TNBC).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
- •Performance Status of 0 or 1
- •Adequate bone marrow, kidney, and liver function
- •Part 2 includes advanced triple negative breast cancer patients.
Exclusion Criteria
- •Brain metastases requiring steroids
- •Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start
- •Active and clinically significant bacterial, fungal or viral infection
Arms & Interventions
Part 1
Intervention: PF-06647263 (Drug)
Outcomes
Primary Outcomes
Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1)
Time Frame: Baseline up to Cycle 2 Day 1 (22 days)
DLTs were defined as any of the following adverse events (AEs) which were not considered related to disease progression occurring in the first cycle of treatment:(1)Hematologic: grade 4 neutropenia lasting \>7 days; febrile neutropenia (defined as neutropenia \>=Grade 3 and a single body temperature \>38.3°C or a sustained temperature of \>=38°C for more than 1 hour); grade \>=3 neutropenia with infection; any grade thrombocytopenia associated with clinically significant or life threatening bleeding; grade 4 thrombocytopenia \>=72 hours or platelets \<=10,000/mm\^3 regardless of duration. (2)Non- hematologic: bilirubin increase \>=2 × upper limit of normal (ULN) and not related to disease progression or other known cause; all other Grade \>=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea); delay by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression.
Percentage of Participants With Objective Response (Part 2)
Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Objective response rate (ORR) refers to percentage of participants who achieved complete response (CR) or partial response (PR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits.
Secondary Outcomes
- Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) (All Causality, All Cycles)(Baseline up to 28 days after the last treatment administration (Approximately 13 months))
- Number of Participants With Vital Signs Abnormalities(Baseline, Days 1, 8, 15 of each cycle, and post treatment period. (Approximately 13 months))
- Area Under the Serum Concentration-time Profile From Time 0 to the 504-hour Time Point (AUC504) of PF-06647263(Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).)
- Clearance (CL) of PF-06647263(QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Terminal Serum Half-life (t1/2) of PF-06647263(Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- AUC504 of Total Antibody(Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).)
- AUCtau of Total Antibody(QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Cmax of Total Antibody(QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Tmax of Total Antibody(QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- CL of Total Antibody(QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Cmax of Unconjugated Payload CL-184538(Every Cycle: Days 1, 8, 15. up to end of treatment (Approximately 13 months))
- Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causality, All Cycles)(Baseline up to 28 days after the last treatment administration (Approximately 13 months))
- Number of Participants With Treatment-Emergent AEs (Treatment-related, All Cycles)(Baseline up to 28 days after the last treatment administration (Approximately 13 months))
- Number of Participants With Treatment-Emergent SAEs (Treatment-related, All Cycles)(Baseline up to 28 days after the last treatment administration (Approximately 13 months))
- Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06647263(QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Progression Free Survival(Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months)
- Maximum Observed Serum Concentration (Cmax) of PF-06647263(QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Time for Cmax (Tmax) of PF-06647963(QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Volume of Distribution at Steady State (Vss) of PF-06647263(QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Vss of Total Antibody(QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- t1/2 of Total Antibody(Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.)
- Number of Participants With Positive Neutralizing Anti PF-06647263 Antibody(QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.)
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)(Baseline up to 7 days post end of treatment (Approximately 13 months))
- Number of Participants With Positive Antibodies for PF-06647263, Total Antibody (PF-06523432), and Unconjugated Payload (CL-184538)(QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.)
- Number of Participants With Treatment-Emergent and Treatment-Boosted Anti PF-06647263 Antibody(QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.)
- Percentage of Participants With Objective Response (Part 1)(Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months)
- Percentage of Participants With Clinical Benefit Response(Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months)
- Overall Survival (OS)-Stratifying for EFNA4 Expression (Part 2)(Baseline up to 24 months)