PF-06671008 Dose Escalation Study in Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT02659631
• Recruitment Status: Terminated
• First Posted: January 20, 2016
• Results First Posted: May 6, 2020
• Last Update Posted: May 6, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: January 15, 2016
• First Posted Date: January 20, 2016
• Results First Submitted Date: March 20, 2020
• Results First Posted Date: May 6, 2020
• Last Update Posted Date: May 6, 2020
• Actual Study Start Date: April 28, 2016
• Actual Primary Completion Date: March 29, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2020)

• Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1 [ Time Frame: Baseline through Day 21 (Cycle 1) ]
  DLT was defined as any of the following adverse events occurring in the first cycle of treatment (21 days after the first dose): a) Hematologic: Febrile neutropenia defined as an absolute neutrophil count (ANC) <1.0 x 10^9/L with a single temperature of >38.3°C, or 101°F, or a sustained temperature of >=38°C, or 100.4°F, for more than one hour; b) Non-hematologic: Delay by more than 2 weeks in receiving the next scheduled dose due to persisting treatment related toxicities; c) Any grade 3 or 4 clinically-relevant hematologic or non-hematologic toxicity.
• Number of Participants With Objective Response (OR) - Part 2 [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
  Number of participants with OR based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

Original Primary Outcome Measures (submitted: January 15, 2016)

• Number of participants with Dose-Limiting Toxicities (DLT) [Part 1] [ Time Frame: Baseline through Day 21 ]
  First cycle DLTs in order to determine the maximum tolerated dose
• Number of participants with objective response [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
  Objective response as determined by RECIST v1.1

Current Secondary Outcome Measures (submitted: April 27, 2020)

• Maximum Serum Concentration (Cmax) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  Maximum serum concentration (Cmax) of PF-06671008 was observed directly from data. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
• Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence.
• Terminal Elimination Half-life (t1/2) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  Terminal elimination half-life (t1/2) of PF-06671008 was calculated as ln(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. Arithmetic mean was not calculated if fewer than 3 participants had reportable parameter values.
• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  Tau refers to the dosing interval, which was 1 week. Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
• Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  AUCinf was calculated as AUClast +(Clast*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
• Systemic Clearance (CL) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  Systemic Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
• Apparent Clearance (CL/F) of PF-06671008 [ Time Frame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose ]
  Apparent Clearance (CL/F) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arm. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
• Number of Participants With OR - Part 1 [ Time Frame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months ]
  Number of participants with OR based on assessment of CR or PR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
• Number of Participants With Progression Free Survival (PFS) - Part 2 [ Time Frame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months ]
  The period from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
• Number of Participants With Overall Survival (OS) - Part 2 [ Time Frame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months ]
  The period from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death).
• Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008 [ Time Frame: C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months ]
  ADA against PF-06671008 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer >=1.18 was considered positive.

Original Secondary Outcome Measures (submitted: January 15, 2016)

• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: C1D1 0, 1, 2, 4, 8, 24 hrs post, D4, D8 0, 1, 2, 4, 8, 24 hrs post, D11, D15 0, 1 or 2 hrs post, C2D1 0, 1 or 2, 4, 24 hrs post, D4, D8 and D15 0, 1 or 2 hrs post, 0, 1 or 2 hrs post on D1, 8 and 15 of subsequent cycles, and up to 24 months ]
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: C1D1 0, 1, 2, 4, 8, 24 hrs post, D4, D8 0, 1, 2, 4, 8, 24 hrs post, D11, D15 0, 1 or 2 hrs post, C2D1 0, 1 or 2, 4, 24 hrs post, D4, D8 and D15 0, 1 or 2 hrs post, 0, 1 or 2 hrs post on D1, 8 and 15 of subsequent cycles, and up to 24 months ]
• Plasma Decay Half-Life (t1/2) [ Time Frame: C1D1 0, 1, 2, 4, 8, 24 hrs post, D4, D8 0, 1, 2, 4, 8, 24 hrs post, D11, D15 0, 1 or 2 hrs post, C2D1 0, 1 or 2, 4, 24 hrs post, D4, D8 and D15 0, 1 or 2 hrs post, 0, 1 or 2 hrs post on D1, 8 and 15 of subsequent cycles, and up to 24 months ]
• Area Under the Curve from Time Zero to End of Dosing Interval (AUCtacu) [ Time Frame: C1D1 0, 1, 2, 4, 8, 24 hrs post, D4, D8 0, 1, 2, 4, 8, 24 hrs post, D11, D15 0, 1 or 2 hrs post, C2D1 0, 1 or 2, 4, 24 hrs post, D4, D8 and D15 0, 1 or 2 hrs post, 0, 1 or 2 hrs post on D1, 8 and 15 of subsequent cycles, and up to 24 months ]
• Area Under the Curve from time zero to infinity (AUCinf) [ Time Frame: C1D1 0, 1, 2, 4, 8, 24 hrs post, D4, D8 0, 1, 2, 4, 8, 24 hrs post, D11, D15 0, 1 or 2 hrs post, C2D1 0, 1 or 2, 4, 24 hrs post, D4, D8 and D15 0, 1 or 2 hrs post, 0, 1 or 2 hrs post on D1, 8 and 15 of subsequent cycles, and up to 24 months ]
• Systemic Clearance [ Time Frame: C1D1 0, 1, 2, 4, 8, 24 hrs post, D4, D8 0, 1, 2, 4, 8, 24 hrs post, D11, D15 0, 1 or 2 hrs post, C2D1 0, 1 or 2, 4, 24 hrs post, D4, D8 and D15 0, 1 or 2 hrs post, 0, 1 or 2 hrs post on D1, 8 and 15 of subsequent cycles, and up to 24 months ]
• Number of participants with objective response (Part 1) [ Time Frame: Baseline and every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months ]
  Response rate by RECIST v1.1
• Number of participants with PFS (Part 2) [ Time Frame: Baseline and every 6 weeks until disease progression or unacceptable toxicity, or up to 24 months ]
• Number of participants with OS (Part 2) [ Time Frame: Baseline and every 6 weeks until disease progression or unacceptable toxicity, or up to 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PF-06671008 Dose Escalation Study in Advanced Solid Tumors
• Official Title: A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06671008 IN PATIENTS WITH ADVANCED SOLID TUMORS
• Brief Summary: The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06671008 in patients with advanced solid tumors with the potential to have P-cadherin expression. The study will then expand to look at the selected dose in patients with P-cadherin expressing TNBC, CRC or NSCLC.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neoplasms

Intervention

• Drug: PF-06671008
  Dose Escalation Phase - Part 1
• Drug: PF-06671008
  Dose Expansion Phase - Part 2

Study Arms

Experimental: PF-06671008

Interventions:

• Drug: PF-06671008
• Drug: PF-06671008

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 9, 2018): 28
• Original Estimated Enrollment (submitted: January 15, 2016): 110
• Actual Study Completion Date: March 29, 2019
• Actual Primary Completion Date: March 29, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria

• Diagnosis of tumor type with the potential to have P-cadherin expression that is resistant to standard therapy or for which no standard therapy is available
• Performance status of 0 or 1
• Adequate bone marrow, kidney and liver function

Key Exclusion Criteria

• Known CNS disease including, but not limited to, metastases
• Current or history of seizure disorder
• History of or active autoimmune disorders
• Active bacterial, fungal or viral infection
• Major surgery, anti-cancer therapy, or radiation therapy within 4 weeks of study treatment
• Requirement for systemic immune suppressive medication
• Grade 2 or greater peripheral neuropathy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02659631
• Other Study ID Numbers: B7831001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: April 2020