Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Head and Neck Neoplasms

Carcinoma, Transitional Cell

Sarcoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplasms, Connective and Soft Tissue

Ovarian Cancer

Ovarian Epithelial Cancer

Transitional Cell Carcinoma

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

PF-06801591

Pfizer CT.gov Call Center

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Cmax was the maximum concentration after dose administration observed directly from the data.

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

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.

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.

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.

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.

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.

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.

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.

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.

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%.

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.

DOSD was analyzed by the Kaplan-Meier approach for each tumor type. Stable disease (SD) was defined as not qualifying for complete response (CR), partial response (PR), or progression. All target lesions must have been assessed. Stable could follow PR only in the rare case that the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer held. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis \< 10 mm). All target lesions must have been assessed. PR was defined as greater than or equal to 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 have been assessed.

DOR was defined as the time from start date (which was the date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. 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.

TTR was the time to confirmed or unconfirmed complete response (CR) or partial response (PR) based on investigator assessment per RECIST v1.1 by tumor type. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must have decreased to normal size (short axis \< 10 mm). All target lesions must have been assessed. PR was defined as greater than or equal to 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 have been assessed.

TTP was the time to objective progression. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. TTP was analyzed by the Kaplan-Meier approach for each tumor type.

Median time to death was analyzed by the Kaplan-Meier approach for each tumor type.

Probability of survival was calculated from the product-limit method.

Trough PF-06801591 Concentrations (Ctrough) - Part 2. Ctrough was directly observed from data.

Pfizer

The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.

Participants received PF-06801591 0.5 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1186 days)

Part 1: PF-06801591 0.5 mg/kg (Intravenously [IV])

Participants received PF-06801591 1 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 659 days)

Part 1: PF-06801591 1 mg/kg (IV)

Participants received PF-06801591 3 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 1606 days)

Part 1: PF-06801591 3 mg/kg (IV)

Participants received PF-06801591 10 mg/kg IV every 3 weeks for 21-day cycles. (maximum of 445 days)

Part 1: PF-06801591 10 mg/kg (IV)

Participants received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 419 days)

Part 1: PF-06801591 300 mg (Subcutaneously [SC])

Participants received PF-06801591 IV every 3 weeks for 21-day cycles in Part 1. (up to a maximum of of 233 weeks)

Part 1: PF-06801591 IV Total

Participants received PF-06801591 IV every 3 weeks for 21-day cycles or SC every 4 weeks for 28-day cycles in Part 1. (up to a maximum of 233 weeks)

Part 1: PF-06801591 IV and SC Total

Participants with NSCLC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 851 days)

Part 2: PF-06801591 300 mg (SC) for NSCLC

Participants with UC received PF- 06801591 300 mg SC every 4 weeks for 28-day cycles. (maximum of 841 days)

Part 2: PF-06801591 300 mg (SC) for UC

Participants with NSCLC or UC received PF-06801591 300 mg SC every 4 weeks for 28-day cycles in Part 2. (up to a maximum of 126 weeks)

Part 2: PF-06801591 NSCLC and UC Total

Total

18-44 Years

45-64 Years

>=65 Years

Age, Customized

Sex: Female, Male

White

Black or African American

Asian

Other

Race/Ethnicity, Customized

Baseline population included all enrolled participants who received at least 1 dose of study treatment. One participant who enrolled in Part 2: PF-06801591 300 mg (SC) for UC arm was not treated.

Pfizer ClinicalTrials.gov Call Center

DLT analysis population included all enrolled participants who received at least 1 dose of study treatment and who did not have major treatment deviations during Cycle 1.

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

Participants with AEs

Participants with SAEs

Participants with maximum Grade 3 or 4 AEs

Participants with maximum Grade 5 AEs

Analysis population included all enrolled participants who received at least 1 dose of study medication.

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

Participants with maximum of Grade 3 or 4 AEs

Participants with maximum of Grade 5 AEs

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

ANEMIA

HEMOGLOBIN INCREASED

LYMPHOCYTE COUNT DECREASED

LYMPHOCYTE COUNT INCREASED

NEUTROPHIL COUNT DECREASED

PLATELET COUNT DECREASED

WHITE BLOOD CELL DECREASED

ALANINE AMINOTRANSFERASE INCREASED

ALKALINE PHOSPHATASE INCREASED

ASPARTATE AMINOTRANSFERASE INCREASED

BLOOD BILIRUBIN INCREASED

CPK INCREASED

CREATININE INCREASED

GGT INCREASED

HYPERCALCEMIA

HYPERGLYCEMIA

HYPERKALEMIA

HYPERMAGNESEMIA

HYPERNATREMIA

HYPOALBUMINEMIA

HYPOCALCEMIA

HYPOGLYCEMIA

HYPOKALEMIA

HYPOMAGNESEMIA

HYPONATREMIA

HYPOPHOSPHATEMIA

LIPASE INCREASED

SERUM AMYLASE INCREASED

PROTEINURIA

ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED

INR INCREASED

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

Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death.

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

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

Cycle 1 Day 1

Cycle 4 Day 1

Analysis population included all enrolled participants treated who were evaluable for this outcome measure.

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

AUClast of PF-06801591 in Part 1.

Clearance (CL) of PF-06801591 - Part 1

The PK parameter analysis population was defined as all enrolled participants in Part 1 who received study drug following IV administration and had sufficient information to estimate at least 1 of the pharmacokinetic (PK) parameters of interest. Number of participants analyzed represents the total number of participants in each treatment group in the PK parameter analysis population. Number analyzed represents the number of participants who had reportable parameter values of Vss.

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

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

The PK parameter analysis population was defined as all enrolled participants in Part 1 who received study drug following IV or SC administration and had sufficient information to estimate at least 1 of the PK parameters of interest. Number of participants analyzed represents the total number of participants in each treatment group in the PK parameter analysis population. Number analyzed represents the number of participants who had reportable parameter values of t1/2.

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

Analysis population included all participants who received at least 1 dose of study treatment and had at least 1 post-treatment ADA result.

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

Analysis population included all participants who received at least 1 dose of study treatment and had at least 1 post-treatment ADA result. NAb-negative participants included participants who were ADA negative or ADA-positive participants who tested negative in the NAb assay.

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

Cycle 1 Day 8

Cycle 1 Day 15

Cycle 1 Day 21

Cycle 2 Day 1

Cycle 3 Day 1

Cycle 4 Day 15

Cycle 4 Day 21

Cycle 5 Day 1

Analysis population included all enrolled participants with at least 1 of the pharmacodynamic/biomarker parameters evaluated at pre- and/or post dose.

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

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

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

RECIST v1.1

irRECIST

This was a combined group of PF-06801591 0.5, 1, 3, and 10 mg/kg (IV) in Part 1. Participants received PF-06801591 0.5, 1, 3, or 10 mg/kg IV every 3 weeks for 21-day cycles. (up to a maximum of 233 weeks).

Part 1: PF-06801591 0.5-10 mg/kg (Intravenously [IV])

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

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

Analysis population included all the randomized participants who received at least 1 dose of study medication, had measurable disease baseline assessment (within 28 days prior to study entry) and at least 1 post baseline assessment or disease progression, global deterioration of health status, or death. DOR was only applicable to those participants with an objective response.

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

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

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

Median Time to Death - Part 2

6 Months

1 Year

2 Years

Analysis population included all the randomized participants who received PF-06801591 and had at least 1 post-dose concentration measurement above the lower limit of quantification (LLQ).

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

Cycle 6 Day 1

Cycle 9 Day 1

Cycle 12 Day 1

Cycle 15 Day 1

Cycle 18 Day 1

Cycle 21 Day 1

Cycle 24 Day 1

Follow-up Day 28

Analysis population included all participants who received PF-06801591, had no protocol deviations affecting the pharmacokinetics (PK) assessment, and had at least 1 post-dose concentration measurement above lower limit of quantification.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
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	NCT02573259	Part 1 MELANOMA SCCHN OVCA SARCOMA OTHER SOLID TUM... Part 1 and 2 NSCLC UROTHELIAL CARC...	PF-06801591 PF-06801591	18 Years -	Pfizer
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	NCT02573259	Part 1 MELANOMA SCCHN OVCA SARCOMA OTHER SOLID TUM... Part 1 and 2 NSCLC UROTHELIAL CARC...	PF-06801591 PF-06801591	18 Years -	Pfizer

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