A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors

• ClinicalTrials.gov Identifier: NCT02573259
• Recruitment Status: Completed
• First Posted: October 9, 2015
• Last Update Posted: January 28, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 6, 2015
• First Posted Date: October 9, 2015
• Last Update Posted Date: January 28, 2021
• Actual Study Start Date: February 10, 2016
• Actual Primary Completion Date: November 19, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2017)

• Percentage of participants with Dose-limiting toxicities (DLT) [ Time Frame: 90 days ]
  A DLT is any of a predefined set of unacceptable adverse events that are observed and that are at least possibly related to the investigational agent(s) OR a DLT is any of a predefined set of unacceptable adverse events (AE), regardless of cause.
• Overall Safety Profile [ Time Frame: approximately 2 years ]
  Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events (AE) and any laboratory abnormalities.
• Estimate clinical efficacy [ Time Frame: Baseline and every 8-12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion (approximately 2 years). ]
  Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria, immune-related RECIST (irRECIST).

Original Primary Outcome Measures (submitted: October 8, 2015)

• Percentage of participants with Dose-limiting toxicities (DLT) [ Time Frame: Day 1 up to day 21 ]
  A DLT is any of a predefined set of unacceptable adverse events that are observed and that are at least possibly related to the investigational agent(s) OR a DLT is any of a predefined set of unacceptable adverse events, regardless of cause.
• Overall Safety Profile [ Time Frame: Day 1 up to Day 21 ]
  Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities.

Current Secondary Outcome Measures (submitted: September 26, 2017)

• Area under the concentration versus time curve (AUCt) [ Time Frame: Baseline through end of treatment, an approximate average of 4 months ]
  AUCt will be calculated for PF- 06801591
• Incidence of anti drug antibodies (ADA) [ Time Frame: Baseline through end of treatment, an approximate average of 4 months ]
  Incidence of anti drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-06801591.
• Percentage of Receptor Occupancy (RO) [ Time Frame: 0hr at Baseline and through end of treatment, an approximate average of 4 months ]
  Percentage RO of PF-06801591 in circulating T cells over time following PF-06801591 administration.
• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0hr at Baseline and through end of treatment; an approximate average of 4 months ]
  Cmax will be calculated for PF-06801591
• Evaluate preliminary anti-tumor activity of PF-06801591 [ Time Frame: Baseline and every 8-12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion (approximately 2 years). ]
  Time to event endpoints based on RECIST and irRECIST, including time to response (TTR) and time to progression (TTP) as well as progression free survival (PFS) and immune-related (ir) PFS (irPFS) as appropriate, duration of stable disease (DOSD) and irDOSD as appropriate, and duration of response (DOR) and irDOR as appropriate.
• Evaluate overall survival [ Time Frame: Approximately 2 years ]
  Median time to death, proportion of patients alive at 6 months, 1 year, and 2 years.

Original Secondary Outcome Measures (submitted: October 8, 2015)

• Area under the concentration versus time curve (AUCt) [ Time Frame: 0hr on Day1, Day 2, Day 8, Day 15, Cycles 2 and 3 Day 1 and Cycle 4 days 1 and 15 and Cycle 5 Day 1 and Day 1 of each subsequent (21 day) cycle through study completion an average of 4 months ]
  AUCt will be calculated for PF- 06801591
• Incidence of anti drug antibodies (ADA) [ Time Frame: 0 hr on Day 1 Cycles 2 (Day 42) and 4 (Day 84), and every other (21 day) cycle (42 days) through study completion an average of 4 months ]
  Incidence of anti drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-06801591.
• Number of patients with ORR (Objective Response Rate) (RECIST) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
  Objective tumor response, as assessed using the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria
• Percentage of Receptor Occupancy [ Time Frame: 0hr on Day1, Day 2, Day 8, Day 15, Cycles 2 and 3 Day 1 (Days 22 and 43) and Cycle 4 days 1 (Day 85) and 15 (Day 100) and Cycle 5 Day 1 (Day 106) ]
  Percentage RO of PF-06801591 in circulating T cells over time following PF-06801591 administration.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0hr on Day1, Day 2, Day 8, Day 15, Cycles 2 and 3 Day 1 (Days 22 and 43) and Cycle 4 days 1 (Day 85) and 15 (Day 100) and Cycle 5 Day 1 (Day 106) and every 21 days after Cycle 5 Day 1 through study completion an average of 4 months ]
  Cmax will be calculated for PF-06801591
• Number of patients with ORR (Objective Response Rate)(irRECIST) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
  Objective tumor response, as assessed using immune related RECIST (irRECIST) criteria
• Number of patients with ORR (Objective Response Rate) (Lymphoma Response) [ Time Frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months ]
  Objective tumor response, as assessed using Lymphoma Response Criteria

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

Descriptive Information

• Brief Title: A Dose Escalation Study Of PF-06801591 In Melanoma, Head And Neck Cancer (SCCHN), Ovarian, Sarcoma, Non-Small Cell Lung Cancer, Urothelial Carcinoma or Other Solid Tumors
• Official Title: A PHASE 1, OPEN-LABEL, DOSE ESCALATION AND EXPANSION STUDY OF PF-06801591 IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC MELANOMA, SQUAMOUS CELL HEAD AND NECK CANCER, OVARIAN CANCER, SARCOMA, NON-SMALL CELL LUNG CANCER, UROTHELIAL CARCINOMA OR OTHER SOLID TUMORS.
• Brief Summary: Protocol B8011001 is a Phase 1, open-label, multi-center, multiple-dose, dose escalation and expansion, safety, pharmacokinetics (PK), and pharmacodynamics (PD) study of PF-06801591 in previously treated adult patients with locally advanced or metastatic melanoma, SCCHN, ovarian carcinoma, sarcoma, NSCLC, urothelial carcinoma or other solid tumors. This is a 2 Part study whereby the safety and tolerability of increasing dose levels of intravenous (IV) or subcutaneous (SC) PF-06801591 was assessed in Part 1. Part 2 expansion is designed to further evaluate the safety and efficacy of SC PF-06801591 in patients with NSCLC or urothelial carcinoma as well as confirm the recommended Phase 2 dose.

Detailed Description

Protocol B8011001 is a Phase 1, two part, open-label, multi center, multiple-dose, safety, efficacy, PK, and PD study of PF-06801591 administered intravenously (IV) or subcutaneous (SC) in previously treated adult patients with locally advanced or metastatic melanoma, squamous cell carcinoma head and neck (SCCHN), ovarian carcinoma, sarcoma, non-small cell lung carcinoma (NSCLC), urothelial carcinoma or other solid tumors.

The first part of the study, Part 1 dose escalation, was designed to assess the safety and tolerability of increasing dose levels of IV or SC administered PF-06801591 to establish the maximum tolerated dose (MTD) using a modified Toxicity Probability Interval (mTPI) design. Part 2 expansion is designed to further evaluate the safety and efficacy of 300 mg of PF-06801591 administered SC once every 4 weeks in patients with NSCLC or urothelial carcinoma as well as confirm the recommended Phase 2 dose (RP2D). Part 1 enrollment has completed, enrollment will only be allowed for Part 2.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Part 1
• MELANOMA
• SCCHN
• OVCA
• SARCOMA
• OTHER SOLID TUMORS
• Part 1 and 2
• NSCLC
• UROTHELIAL CARCINOMA

Intervention

• Drug: PF-06801591
  IV every 21 days (Part 1)
• Drug: PF-06801591
  300 mg SC every 28 days (Part 1 and 2)

Study Arms

• Experimental: Arm 1 PF-06801591
  0.5 mg/kg IV every 21 days (Part 1)
  Intervention: Drug: PF-06801591
• Experimental: Arm 2 PF-06801591
  1.0 mg/kg IV every 21 days (Part 1)
  Intervention: Drug: PF-06801591
• Experimental: Arm 3 PF-06801591
  3.0 mg/kg IV every 21 days (Part 1)
  Intervention: Drug: PF-06801591
• Experimental: Arm 4 PF-06801591
  10 mg/kg IV every 21 days (Part 1)
  Intervention: Drug: PF-06801591
• Experimental: Arm 5 PF-06801591
  300 mg SC every 28 days (Part 1 and 2)
  Intervention: Drug: PF-06801591

• Publications *: Johnson ML, Braiteh F, Grilley-Olson JE, Chou J, Davda J, Forgie A, Li R, Jacobs I, Kazazi F, Hu-Lieskovan S. Assessment of Subcutaneous vs Intravenous Administration of Anti-PD-1 Antibody PF-06801591 in Patients With Advanced Solid Tumors: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2019 Jul 1;5(7):999-1007. doi: 10.1001/jamaoncol.2019.0836.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 15, 2019): 147
• Original Estimated Enrollment (submitted: October 8, 2015): 180
• Actual Study Completion Date: November 19, 2020
• Actual Primary Completion Date: November 19, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria (Part 2 Only):

• Histological or cytological diagnosis of locally advanced or metastatic NSCLC or urothelial carcinoma who have progressed on or were intolerant to standard of care systemic therapy, or for whom standard of care systemic therapy was refused (refusal must be documented) or unavailable.
• No prior treatment with anti-PD-1 or anti-PD-L1 therapy.
• NSCLC patients whose tumor is not known to have ALK or EGFR mutations must have progressed on or after no more than 1 prior line of platinum-containing systemic therapy or were intolerant or refused standard of care systemic therapy.
• NSCLC patients whose tumor is known to have ALK or EGFR mutation must have received prior systemic therapies that only include 1 or more lines of ALK or EGFR targeting drugs and chemotherapy limited to 1 line of a platinum-based regimen and they must have progressed on or after both types of therapies.
• Urothelial carcinoma patients must have received up to 2 lines of prior systemic therapy and progressed on or after, experienced disease recurrence within 12 months of neoadjuvant or adjuvant treatment, were intolerant to, ineligible or refused platinum-containing systemic therapy. If urothelial cancer patients are treatment naïve and eligible for platinum-containing systemic therapy but are refusing platinum chemotherapy, they must also be documented to have previous PD-L1 high status.
• Provide archived tumor tissue sample taken within the past 2 years or provide a fresh tumor biopsy sample.
• At least one measurable lesion as defined by RECIST version 1.1.
• Adequate renal, liver, thyroid and bone marrow function.
• Performance status 0 or 1.
• Patient is capable of receiving study treatment for at least 8 weeks.

Exclusion Criteria (Part 2 Only)

• Active brain or leptomeningeal metastases.
• Active, known or suspected autoimmune disease. Patients with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy or prior allogeneic bone marrow or hematopoietic stem cell transplant.
• Patients with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Patients with a history of interstitial lung disease, non-infectious pneumonitis, or active pulmonary tuberculosis. Those with active lung infections requiring treatment are also excluded.
• History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy.
• Active hepatitis B or C, HIV/AIDS.
• Other potentially metastatic malignancy within past 5 years.

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: Bulgaria, Korea, Republic of, Malaysia, Poland, Russian Federation, Ukraine, United States
• Removed Location Countries: Singapore

Administrative Information

• NCT Number: NCT02573259
• Other Study ID Numbers: B8011001; 2016-003314-27 ( EudraCT Number )
• 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: January 2021