NCT02573259 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2021-12-13

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Percentage of Participants With Dose-Limiting Toxicities (DLT) - Part 1

→

outcome · POSTED

Number of Participants With All-Causality Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2

→

outcome · POSTED

Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2

→

outcome · POSTED

Number of Participants With Laboratory Test Abnormalities - Part 1 and Part 2

→

outcome · POSTED

Objective Response Rate (ORR) Based on RECIST Version 1.1 - Part 2

→

outcome · POSTED

Objective Response Rate (ORR) Based on Immune Related RECIST (irRECIST) - Part 2

→

outcome · POSTED

Maximum Plasma Concentration (Cmax) of PF-06801591 - Part 1

→

outcome · POSTED

AUClast of PF-06801591 in Part 1.

→

outcome · POSTED

Clearance (CL) of PF-06801591 - Part 1

→

outcome · POSTED

Volume of Distribution at Steady State (Vss) of PF-06801591 - Part 1

→

outcome · POSTED

Accumulation Ratio (Rac) of PF-06801591 - Part 1

→

outcome · POSTED

Terminal Elimination Half-Life (t1/2) of PF-06801591 - Part 1

→

outcome · POSTED

Number of Participants With Anti-Drug Antibody (ADA) Against PF-06801591 - Part 1 and Part 2

→

outcome · POSTED

Number of Participants With Neutralizing Antibodies (NAb) Positive Against PF-06801591 - Part 1 and Part 2

→

outcome · POSTED

Percentage of Baseline PD-1 Receptor Occupancy (RO) by PF-06801591 - Part 1

→

outcome · POSTED

Number of Participants Achieving Objective Response (OR) Based on RECIST Version 1.1 - Part 1

→

outcome · POSTED

Number of Participants Achieving Objective Response (OR) Based on irRECIST - Part 1

→

outcome · POSTED

Progression-Free Survival (PFS) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2

→

outcome · POSTED

Duration of Stable Disease (DOSD) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2

→

outcome · POSTED

Duration of Response (DOR) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2

→

outcome · POSTED

Time to Response (TTR) Based on RECIST Version 1.1 - Part 2

→

outcome · POSTED

Time to Progression (TTP) Based on RECIST Version 1.1 and irRECIST - Part 2

→

outcome · POSTED

Median Time to Death - Part 2

→

outcome · POSTED

Probability of Survival at 6 Months, 1 Year, and 2 Years - Part 2

→

outcome · POSTED

Trough PF-06801591 Concentrations (Ctrough) - Part 2

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
0.5 mg/kg IV every 21 days (Part 1)
intervention Names
Drug: PF-06801591
label
Arm 1 PF-06801591
type
EXPERIMENTAL
description
1.0 mg/kg IV every 21 days (Part 1)
intervention Names
Drug: PF-06801591
label
Arm 2 PF-06801591
type
EXPERIMENTAL
description
3.0 mg/kg IV every 21 days (Part 1)
intervention Names
Drug: PF-06801591
label
Arm 3 PF-06801591
type
EXPERIMENTAL
description
10 mg/kg IV every 21 days (Part 1)
intervention Names
Drug: PF-06801591
label
Arm 4 PF-06801591
type
EXPERIMENTAL
description
300 mg SC every 28 days (Part 1 and 2)
intervention Names
Drug: PF-06801591
label
Arm 5 PF-06801591
type
EXPERIMENTAL

interventions

arm Group Labels
Arm 1 PF-06801591
Arm 2 PF-06801591
Arm 3 PF-06801591
Arm 4 PF-06801591
description
IV every 21 days (Part 1)
name
PF-06801591
type
DRUG
arm Group Labels
Arm 5 PF-06801591
description
300 mg SC every 28 days (Part 1 and 2)
name
PF-06801591
type
DRUG

Study design

allocation

NON_RANDOMIZED

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 147
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
DLT was defined as any of the following drug-related adverse events (AEs) occurring during the first cycle (21 days for IV dosing, 28 days for SC dosing) in Part 1: Grade 5 AE; Grade 4 neutropenia lasting \>5 days from initiation of granulocyte colony stimulating factor; Grade 4 thrombocytopenia with bleeding; Platelet transfusion requirement or a platelet count \<10,000/uL; Grade 4 non-hematologic AE; Grade 3 AE lasting \>7 days despite optimal supportive care; Grade 3 central nervous system AE regardless of duration; met criteria for drug induced liver injury. Severity of AEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
measure
Percentage of Participants With Dose-Limiting Toxicities (DLT) - Part 1
time Frame
Cycle 1 in Part 1 (21 days for IV administration of PF-06801591; 28 days for SC administration of PF-06801591)
description
AE = any untoward medical occurrence in participant who received study treatment without regard to possibility of causal relationship. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Grades of severity were defined by CTCAE v4.03. Grades of severity were defined by CTCAE v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
measure
Number of Participants With All-Causality Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
time Frame
Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
description
Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Treatment-emergent events = between first dose of study treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-related AEs and SAEs were determined by the investigator. Grades of severity were defined by CTCAE v4.03. Grades of severity were defined by CTCAE v4.03. Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
measure
Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) - Part 1 and Part 2
time Frame
Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
description
Following parameters were analyzed for laboratory examination: hematology (anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, white blood cell decreased); chemistries (increase of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, blood bilirubin, CPK, creatinine, gamma-glutamyl transferase \[GGT\], lipase, and serum amylase); urinalysis (proteinuria); coagulation (activated partial thromboplastin time prolonged, international normalized ratio \[INR\] increased). Grades of severity were defined by CTCAE v4.03. Grade 0 = No Change from normal or reference range (this grade is not included in the CTCAE v4.03 document but may used in certain circumstances). Grade 1 = mild adverse event (AE). Grade 2 = moderate AE; Grade 3 = severe AE. Grade 4 = life-threatening consequences; urgent intervention indicated. Grade 5 = death related to AE.
measure
Number of Participants With Laboratory Test Abnormalities - Part 1 and Part 2
time Frame
Baseline up to 28 days after last dose of study treatment (maximum of 1634 days)
description
ORR was defined as percentage of participants with confirmed objective response (OR) of complete response (CR) and partial response (PR) based on RECIST version 1.1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). All target lesions must be assessed. PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
measure
Objective Response Rate (ORR) Based on RECIST Version 1.1 - Part 2
time Frame
Baseline up to end of treatment in Part 2 (maximum of 851 days)
description
ORR was defined as percentage of participants with objective response (OR) of complete response (CR) and partial response (PR) based on irRECIST. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). All target lesions must be assessed. PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
measure
Objective Response Rate (ORR) Based on Immune Related RECIST (irRECIST) - Part 2
time Frame
Baseline up to end of treatment in Part 2 (maximum of 851 days)

secondary Outcomes

description
Cmax was the maximum concentration after dose administration observed directly from the data.
measure
Maximum Plasma Concentration (Cmax) of PF-06801591 - Part 1
time Frame
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
description
Area Under the Concentration Versus Time Curve (AUC) From Time Zero to the Last Quantifiable Time Point Prior to the Next Dose (AUClast) of PF-06801591 - Part 1
measure
AUClast of PF-06801591 in Part 1.
time Frame
Pre-dose, 1 and 24 hours post dose on Cycle 1 Day 1 in Part 1
description
CL for IV dosing. CL was calculated by dose / AUCtau for Cycles 1 and 4 IV dosing. AUCtau was defined as area under the serum concentration time profile from time zero to time tau, the dosing interval, where tau = 504 hours for every 3 weeks (Q3W) IV dosing reporting arm.
measure
Clearance (CL) of PF-06801591 - Part 1
time Frame
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
description
Steady state volume of distribution of PF-0680159 for IV dosing. Vss was calculated by CL\*MRT. CL was the clearance for IV dosing. MRT was the mean residence time calculated for a single IV dose as AUMCinf/AUCinf - (DOF/2). AUMCinf was the area under the moment curve from time 0 extrapolated to infinity. DOF was the duration of infusion. AUCinf was the area under the serum concentration time profile from time 0 extrapolated to infinity.
measure
Volume of Distribution at Steady State (Vss) of PF-06801591 - Part 1
time Frame
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
description
Rac was calculated by (Cycle 4 AUCtau) / (Cycle 1 AUCtau). AUCtau was Area under the serum concentration time profile from time zero to time tau, the dosing interval, where tau = 504 hours for Q3W IV dosing and tau = 672 hours for every 4 weeks (Q4W) SC dosing.
measure
Accumulation Ratio (Rac) of PF-06801591 - Part 1
time Frame
Pre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1
description
t1/2 was calculated by Loge(2)/kel. 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.
measure
Terminal Elimination Half-Life (t1/2) of PF-06801591 - Part 1
time Frame
Pre-dose and 1 hour post dose on Day 1 of Cycles 1 and 4 in Part 1
description
Number of participants with ADA positive against PF-06801591 after IV and SC dosing - Part 1 and Part 2. A participant was ADA positive if (1) baseline titer was missing or negative and participant had ≥ 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ≥ 0.602 in titer from baseline in ≥ 1 post-treatment sample (treatment-boosted). Participants who were ADA positive at baseline but did not become boosted post-treatment were considered as ADA negative.
measure
Number of Participants With Anti-Drug Antibody (ADA) Against PF-06801591 - Part 1 and Part 2
time Frame
Baseline up to end of treatment (maximum of 851 days)
description
Number of participants with NAb positive against PF-06801591 after IV and SC dosing - Part 1 and Part 2. A participant was NAb positive if (1) baseline titer was missing or negative and participant had ≥ 1 post-treatment positive titer (treatment-induced), or (2) positive titer at baseline and had a ≥ 0.602 in titer from baseline in ≥ 1 post-treatment sample (treatment-boosted). Participants who were NAb positive at baseline but did not become boosted post-treatment were considered as NAb negative.
measure
Number of Participants With Neutralizing Antibodies (NAb) Positive Against PF-06801591 - Part 1 and Part 2
time Frame
Baseline up to end of treatment (maximum of 851 days)
description
PD-1 RO by sasanlimab was measured by the reduction of free receptor on the surface of CD8+ effector cells (CD3+, CD4-, CD8+, CD45RA+, CCR7-, CD279+) and CD8+ effector memory cells (CD3+, CD4-, CD8+, CD45RA-, CCR7-, CD279+) presented in pre- and postdose whole blood samples by flow cytometry. Percentage of baseline (ie, normalized change from baseline) PD-1 RO were calculated as \[(percentage of cells at Cycle X Day X)/(percentage of cells at baseline)\]\*100, and are reported for this outcome measure. Baseline was defined as the most recent non-missing value prior to dosing.
measure
Percentage of Baseline PD-1 Receptor Occupancy (RO) by PF-06801591 - Part 1
time Frame
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)
description
Number of participants achieving confirmed OR based on RECIST version 1.1 in Part 1. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \< 10 mm). All target lesions must be assessed. PR was defined as \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
measure
Number of Participants Achieving Objective Response (OR) Based on RECIST Version 1.1 - Part 1
time Frame
Baseline up to end of treatment in Part 1 (maximum of 1606 days)
description
Number of participants achieving confirmed OR based on irRECIST in Part 1. OR = irCR + irPR. Overall immune related complete response (irCR) was defined as complete disappearance of all lesions (whether measurable or not) and no new lesions. All measurable lymph nodes also must have a reduction in short axis to \<10 mm. Overall immune related partial response (irPR) was defined as sum of the diameters (longest for non nodal lesions, shortest for nodal lesions) of target and new measurable lesions decreases \>=30%.
measure
Number of Participants Achieving Objective Response (OR) Based on irRECIST - Part 1
time Frame
Baseline up to end of treatment in Part 1 (maximum of 1606 days)
description
PFS was defined as the time from initiation of study intervention to first documentation of tumor progression or to death due to any cause, whichever occurred first. PFS was analyzed by the Kaplan-Meier approach for each tumor type. As this outcome measure was a secondary endpoint defined in the protocol to investigate preliminary signal of efficacy, the results were analyzed and are reported for Part 1 dose-escalation groups combined to provide more statistically meaningful results, instead of results analyzed by dose level with very limited number of participants in each group.
measure
Progression-Free Survival (PFS) Based on RECIST Version 1.1 and irRECIST - Part 1 and Part 2
time Frame
Baseline up to end of treatment (maximum of 1606 days)

Full study description

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.

Source references

references

citation
Sako C, Duan C, Maresca K, Kent S, Schmidt TG, Aerts HJWL, Parikh RB, Simon GR, Jordan P. Real-World and Clinical Trial Validation of a Deep Learning Radiomic Biomarker for PD-(L)1 Immune Checkpoint Inhibitor Response in Advanced Non-Small Cell Lung Cancer. JCO Clin Cancer Inform. 2024 Dec;8:e2400133. doi: 10.1200/CCI.24.00133. Epub 2024 Dec 13.
pmid
39671539
type
DERIVED
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.
pmid
34694529
type
DERIVED
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.
pmid
31145415
type
DERIVED