Clinical trial NCT02573259: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Part 1
MELANOMA
SCCHN
OVCA
SARCOMA
OTHER SOLID TUMORS
Part 1 and 2
NSCLC
UROTHELIAL CARCINOMA
Keywords: efficacy
safety
pharmacokinetics
pharmacodynamics
open label
dose response
multiple ascending dose
immunogenicity
recommended phase 2 dose
subcutaneous
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2015-10-09
Enrollment: 147
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percentage of Participants With Dose-Limiting Toxicities (DLT) - Part 1
timeFrame: Cycle 1 in Part 1 (21 days for IV administration of PF-06801591; 28 days for SC administration of PF-06801591)
measure: Number of Participants With All-Causality Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
timeFrame: Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
measure: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
timeFrame: Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
measure: Number of Participants With Laboratory Test Abnormalities - Part 1 and Part 2
timeFrame: Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
measure: Objective Response Rate (ORR) Based on RECIST Version 1.1 - Part 2
timeFrame: Baseline up to end of treatment in Part 2 (maximum of 851 days)
measure: Objective Response Rate (ORR) Based on Immune Related RECIST (irRECIST) - Part 2
timeFrame: Baseline up to end of treatment in Part 2 (maximum of 851 days)
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of PF-06801591 - Part 1
timeFrame: Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1
measure: AUClast of PF-06801591 in Part 1.
timeFrame: Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1 in Part 1
measure: Clearance (CL) of PF-06801591 - Part 1
timeFrame: Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1
measure: Volume of Distribution at Steady State (Vss) of PF-06801591 - Part 1
timeFrame: Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1, and pre-dose and 1 hour post dose on Cycle 4 Day 1 in Part 1
measure: Accumulation Ratio (Rac) of PF-06801591 - Part 1
timeFrame: Pre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1
measure: Terminal Elimination Half-Life (t1/2) of PF-06801591 - Part 1
timeFrame: Pre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1
measure: Number of Participants With Anti-Drug Antibody (ADA) Against PF-06801591 - Part 1 and Part 2
timeFrame: Baseline up to end of treatment (maximum of 851 days)
measure: Number of Participants With Neutralizing Antibodies (NAb) Positive Against PF-06801591 - Part 1 and Part 2
timeFrame: Baseline up to end of treatment (maximum of 851 days)
measure: Percentage of Baseline PD-1 Receptor Occupancy (RO) by PF-06801591 - Part 1
timeFrame: Baseline, Days 1, 8, 15, 21 of Cycle 1, Day 1 of Cycles 2, 3, 5, Days 1, 15, 21 of Cycle 4, and end of treatment (EOT) in Part 1 (cycle = 21 days for IV dosing; cycle = 28 days for SC dosing)
measure: Number of Participants Achieving Objective Response (OR) Based on RECIST Version 1.1 - Part 1
timeFrame: Baseline up to end of treatment in Part 1 (maximum of 1606 days)
measure: Number of Participants Achieving Objective Response (OR) Based on irRECIST - Part 1
timeFrame: Baseline up to end of treatment in Part 1 (maximum of 1606 days)
measure: Progression-Free Survival (PFS) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
timeFrame: Baseline up to end of treatment (maximum of 1606 days)
measure: Duration of Stable Disease (DOSD) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
timeFrame: Baseline up to end of treatment (maximum of 1606 days)
measure: Duration of Response (DOR) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
timeFrame: Baseline up to end of treatment (maximum of 1606 days)
measure: Time to Response (TTR) Based on RECIST Version 1.1 - Part 2
timeFrame: Baseline up to end of treatment in Part 2 (maximum of 851 days)
measure: Time to Progression (TTP) Based on RECIST Version 1.1 and irRECIST - Part 2
timeFrame: Baseline up to end of treatment in Part 2 (maximum of 851 days)
measure: Median Time to Death - Part 2
timeFrame: Baseline up to end of treatment in Part 2 (maximum of 851 days)
measure: Probability of Survival at 6 Months, 1 Year, and 2 Years - Part 2
timeFrame: Baseline up to end of treatment in Part 2 (maximum of 851 days)
measure: Trough PF-06801591 Concentrations (Ctrough) - Part 2
timeFrame: Pre-dose on Day 1 of Cycles 2-6, 9, 12, 15, 18, 21, 24, and Follow-up Day 28 in Part 2
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Clinical Research Unit
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan Medical Center, Department of Radiological Sciences
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology & Oncology Clinic
state: California
city: Santa Monica
country: United States
facility: Santa Monica UCLA Hematology & Oncology Clinic
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute, Multidisciplinary Clinic
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, Norton Healthcare Pavilion
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital
state: Kentucky
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals, The University of North Carolina at Chapel Hill
state: North Carolina
city: Dickson
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Panagyurishte
country: Bulgaria
facility: MHAT Uni Hospital OOD
state: Pazardzhik
city: Plovdiv
country: Bulgaria
facility: Complex Oncology Center - Plovdiv EOOD
city: Sofia
country: Bulgaria
facility: "MHAT for Women Health - Nadezhda" OOD
city: Varna
country: Bulgaria
facility: SHATOD "Dr. Marko Antonov Markov - Varna" EOOD
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Division of Medical Oncology, Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
state: Johor
city: Lembah Pantai
country: Malaysia
facility: University Malaya Medical Centre
state: Kuala Lumpur
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Kuching
country: Malaysia
facility: Clinical Research Centre(Crc), Hospital Umum Sarawak
state: Sarawak
city: Gdynia
country: Poland
facility: Szpitale Pomorskie Sp. z.o.o., Oddzial Onkologii i Radioterapii
city: Grudziadz
country: Poland
facility: Regionalny Szpital Specjalistyczny im. dr. Wl. Bieganskiego w Grudziadzu
city: Krakow
country: Poland
facility: Centrum Badan Klinicznych JCI Life Science Park
city: Ostroleka
country: Poland
facility: Mazowiecki Szpital Specjalistyczny im. Dr. Jozefa Psarskiego w Ostrolece, Osrodek Onkologiczny
city: Otwock
country: Poland
facility: Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im.Marii Sklodowskiej-Curie
city: Vsevolozhsky District
country: Russian Federation
facility: Sbhi "Lrcod"
state: Leningrad Region
city: Pesochny Village
country: Russian Federation
facility: SBHI ¨Saint-Petersburg clinical scientific practical center of specialized types of
state: Saint-petersburg
city: Chelyabinsk
country: Russian Federation
facility: SBHI "ChRCCO and NM"
city: Moscow
country: Russian Federation
facility: MROI n.a. P.A. Gertsen, filiation of FSBI "NMRC of radiology" MoH Russia
city: Omsk
country: Russian Federation
facility: BHI of Omsk Region "Clinical Oncology Dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: Joint Stock Company Current medical technologies
city: Saint-Petersburg
country: Russian Federation
facility: Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBHI "City Clinical Oncology Dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: SPb SBHI "City Clinical Oncology Dispensary"
city: St. Petersburg
country: Russian Federation
facility: Joint-Stock Company Current medical technologies
city: Yaroslavl
country: Russian Federation
facility: SBHI YaR ¨Regional clinical oncology hospital¨
city: Dnipro
country: Ukraine
facility: Communal Non-profit Institution "City Clinical Hospital #4" of Dnipro City Council, Department of
city: Ivano-Frankivsk
country: Ukraine
facility: Communal non-Commercial Enterprise "Prykarpatski Clinical Oncological Center of Ivano-
city: Kharkiv
country: Ukraine
facility: Grigoriev Radiological Institute of the National Academy of Medical Sciences of Ukraine,
city: Kharkiv
country: Ukraine
facility: Communal Non-profit Institution of Kharkiv Regional Council "Regional Clinical Specialized Health
city: Kyiv
country: Ukraine
facility: "Specialized Clinic "Prognosis Optima" LLC
city: Sumy
country: Ukraine
facility: Communal noncommercial enterprise Sumy regional Rada Sumy regional clinical oncologic dispensary,
city: Uzhhorod
country: Ukraine
facility: Communal Non-profit Institution "Central City Clinical Hospital" of Uzhhorod City Council,
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Oncological Hospital
city: Zaporizhzhya
country: Ukraine
facility: Communal Institution ¨Zaporizhzhya Regional Clinical Oncological Dispensary¨
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Hu-Lieskovan S, Braiteh F, Grilley-Olson JE, Wang X, Forgie A, Bonato V, Jacobs IA, Chou J, Johnson ML. Association of Tumor Mutational Burden and Immune Gene Expression with Response to PD-1 Blockade by Sasanlimab Across Tumor Types and Routes of Administration. Target Oncol. 2021 Nov;16(6):773-787. doi: 10.1007/s11523-021-00833-2. Epub 2021 Oct 25.
citation: 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.