A Study of PF-05082566 In Combination With Mogamulizumab In Patients With Advanced Solid Tumors

Advanced/Metastatic Solid Tumors Clinical Trial

Official title:

A PHASE 1B STUDY OF PF-05082566 IN COMBINATION WITH MOGAMULIZUMAB (KW-0761) IN PATIENTS WITH ADVANCED SOLID TUMORS

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02444793
• Other study ID #: B1641004
• Status: Terminated
• Phase: Phase 1
• Start date: May 2015
• Est. completion date: October 2017

Study information

• Verified date: February 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a Phase 1b, open label, multi center, multi-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended dose for phase 2 (RP2D) investigations of PF- 05082566 in combination with KW-0761 (mogamulizumab) in patients with advanced solid tumors. Once the MTD of PF-05082566 administered in combination with KW-0761 is estimated (dose finding), one or more expansion cohorts of patients with selected advanced solid tumors (dose-expansion ) will be enrolled to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarkers modulation.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: October 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.

• Measurable disease by RECIST version 1.1.

• For Expansion Cohorts only: patients must have tumor accessible for biopsies (core needle biopsy or excision preferred).

• Age 18 years.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Adequate bone marrow, renal and liver function.

• Serum/urine pregnancy test (for females of childbearing potential) negative at screening and before the patient will receive the study treatment.

• Male and female patients of childbearing potential and at risk for pregnancy must agree to use two (2) highly effective methods of contraception throughout the study and for 60 days after the last dose of assigned study treatment.

Exclusion Criteria:

• Active central nervous system primary or secondary malignancies, active seizure disorder, spinal cord compression, or carcinomatous meningitis.

• Therapeutic or experimental monoclonal antibodies in last 60 days prior registration.

• Systemic anticancer therapy or major surgery within 28 days prior to registration. In absence of toxicity from prior systemic anticancer therapy, 5 half-lives since completion of prior systemic anticancer therapy is allowed.

• Systemic steroids, any other form of immunosuppressive therapy or radiation therapy within 14 days prior to registration.

• Live vaccine within 30 days prior to registration.

• Severe hypersensitivity reaction to treatment with another monoclonal antibody, known or suspected hypersensitivity to study drugs or any component of their formulation.

• History of autoimmune disease or known inflammatory bowel disease.

• Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy) or any of the following within 12 months prior to registration: myocardial infarction, congenital long QT syndrome, torsade de points, arrhythmias, right bundle branch block and left anterior hemiblock uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, ongoing NCICTCAE Grade 2 cardiac dysrhythmias, atrial fibrillation or QTcF interval >470 msec.

Related Conditions & MeSH terms

• Advanced/Metastatic Solid Tumors

Intervention

Drug:
• PF-05082566
Part 1: PF-05082566 dose escalation; Increased doses of PF-05082566 IV are administered at appropriate intervals. Part 2: MTD of PF-05082566 IV established in Part 1 is administered.
• KW-0761
Part 1: KW-0761 IV administered at appropriate intervals. Part 2: KW-0761 IV administered at appropriate intervals at the MTD dose for the combination.

Locations

Country	Name	City	State
United States	UNC Cancer Hospital Infusion Pharmacy	Chapel Hill	North Carolina
United States	UNC Hospitals, University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Institute	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Henry Ford Hospital Research Pharmacy	Detroit	Michigan
United States	Tennessee Oncology, PLLC	Gallatin	Tennessee
United States	UC San Diego Medical Center - La Jolla(Thornton Hospital)	La Jolla	California
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	University Of California / San Diego Moores Cancer Center	La Jolla	California
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	UC San Diego Medical Center - Hillcrest	San Diego	California
United States	Sanford Cancer Center	Sioux Falls	South Dakota
United States	Sanford Research	Sioux Falls	South Dakota
United States	Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Georgetown University	Washington	District of Columbia
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Medstar Georgetown University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Pfizer	Kyowa Hakko Kirin Co., Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities (DLT)	DLTs was defined as any of the following adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at first 2 Cycles. Hematologic: (1) Grade 4 neutropenia lasting >7 days; (2) Febrile neutropenia, defined as absolute neutrophil count (ANC) <1000/mm3 with a single temperature of >38.3 degrees C (101 degrees F) or a sustained temperature of >=38 degrees C (100.4 degrees F) for more than 1 hour; (3) Grade >=3 neutropenic infection; (4) Grade >=3 thrombocytopenia with bleeding; (5) Grade 4 thrombocytopenia. Non-Hematologic: (1) Grade >=3 non laboratory toxicities (excluding infusion reactions), except those that had not been maximally treated (eg, nausea, vomiting, diarrhea); (2) Grade >=3 laboratory abnormalities (other than aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) if: Medical intervention was required to treat the participant, or The abnormality led to hospitalization; (3) Grade 4 AST and ALT increase.	First 2 Cycles (28 days in each cycle)
Secondary	Number of Participants With Treatment-Emergent Adverse Events (All Causalities)	An AE was any untoward medical occurrence in a participant administered a product or medical device without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions); resulted in congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs.	Day 1 up to 60 days after last dose of study treatment
Secondary	Number of Participants With Treatment-Emergent Adverse Events (PF-05082566 Related)	An AE was any untoward medical occurrence in a participant administered a product or medical device has a causal relationship with PF-05082566. SAEs were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions); resulted in congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs.	Day 1 up to 60 days after last dose of study treatment
Secondary	Number of Participants With Treatment-Emergent Adverse Events (Mogamulizumab Related)	An AE was any untoward medical occurrence in a participant administered a product or medical device has a causal relationship with Mogamulizumab. SAEs were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions); resulted in congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to NCI CTCAE version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). AEs included non-serious AEs and SAEs.	Day 1 up tp 60 days after last dose of study treatment
Secondary	Number of Participants With Hematology Laboratory Abnormalities as Characterized by Type, Frequency, Severity (as Graded by NCI CTCAE) -Grades 3 or 4	The hematology laboratory tests include: Anemia, Hemoglobin increased, Lymphocyte count increased, Lymphopenia, Neutrophils (absolute), Platelets, White blood cells.	Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
Secondary	Number of Participants With Chemistries Laboratory Abnormalities as Characterized by Type, Frequency, Severity (as Graded by NCI CTCAE) -Grades 3 or 4	The chemistry laboratory tests included: Alanine aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Lactate Dehydrogenase, Sodium, Potassium, Magnesium, Total Calcium, Phosphorus or Phosphate, Total bilirubin, Creatinine or creatinine clearance, Albumin, Total proteins, Uric Acid, BUN or Urea, Immunoglobulin G, Glucose (fasted).	Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
Secondary	Number of Participants With Clinical Significant Observations in Vital Signs	Blood pressure (BP) and pulse rate were recorded in supine or sitting position.	Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
Secondary	Number of Participants With Significant Changes From Baseline in Physical Examination	Physical examination included an examination of major body systems, including general, head, ears, eyes, nose, mouth, throat, neck, lungs, heart, abdomen, musculoskeletal, lymph nodes, neurological and external genitalia. Significant changes from baseline were reported in each category.	Cycle 2 Day 1; End of the treatment.
Secondary	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Shift to Grades 2, 3, 4 or 5	ECOG performance status was classified as 5 grades: 0 (Fully active, able to carry on all predisease performance without restriction); 1 (Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, ie, light house work, office work); 2 (Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours); 3 (Capable of only limited self care, confined to bed or chair more than 50% of waking hours); 4 (Completely disabled. Cannot carry on any self care. Totally confined to bed or chair); 5 (Death). On-study shifts to ECOG performance statuses of 2, 3, 4 or 5 were reported.	Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment
Secondary	Maximum Observed Serum Concentration (Cmax) of PF-05082566-Cycle 5	Maximum Observed Serum Concentration (Cmax) was observed directly from the data.	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	Dose Normalized Cmax of PF-05082566-Cycle 5	Dose normalized Cmax was calculated by Cmax / Dose	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	Cmax of Mogamulizumab-Cycles 1 and 5	Maximum Observed Serum Concentration (Cmax) was observed directly from the data.	Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Pre-dose Concentration During Multiple Dosing (Ctrough) of PF-05082566-Cycle 5	Pre-dose Concentration during Multiple Dosing (Ctrough) was observed directly from data	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	Ctrough of Mogamulizumab- Cycle 5	Pre-dose Concentration during Multiple Dosing (Ctrough) was observed directly from data.	Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Time for Cmax (Tmax) of PF-05082566-Cycle 5	Time for Cmax (Tmax) was observed directly from the data.	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	Time of Last Measurable Concentration (Tlast) of PF-05082566-Cycle 5	Time of last measurable concentration was observed directly from data.	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	Tmax of Mogamulizumab-Cycles 1 and 5	Time for Cmax (Tmax) was observed directly from the data.	Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Tlast of Mogamulizumab-Cycles 1 and 5	Time of last measurable concentration was observed directly from the data.	Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Area Under the Serum Concentration-time Profile From Time 0 to the Time of the Last Measurable Concentration (AUClast) of PF-05082566-Cycle 5	AUClast was area under the serum concentration-time profile from time 0 to the time of the last measurable concentration (Clast), which was measured by Linear/Log trapezoidal method.	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	Dose Normalized AUClast of PF-05082566-Cycle 5	Dose normalized AUClast was calculated by AUClast / Dose	Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.
Secondary	AUClast of Mogamulizumab-Cycles 1 and 5	AUClast was area under the serum concentration-time profile from time 0 to the time of the last measurable concentration (Clast), which was measured by Linear/Log trapezoidal method.	Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Area Under the Serum Concentration-time Profile From Time 0 to 168 Hours (AUC168) of Mogamulizumab-Cycle 1	AUC168 was area under the serum concentration-time profile from time 0 to 168 hours post dose (Cycle 1 only where dosing was once a week), which was measured by Linear/Log trapezoidal method.	Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22
Secondary	Area Under the Serum Concentration-time Profile From Time 0 to Time Tau (AUCtau) of Mogamulizumab-Cycle 5	AUCtau was area under the serum concentration-time profile from time 0 to time tau, the dosing interval, where tau=336 hours	Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Clearance (CL) of Mogamulizumab-Cycle 5	Clearance (CL) was measured by Dose / AUCtau	Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15
Secondary	Anti-Drug Antibody (ADA) Titer for PF-05082566	Serum samples were assayed for ADA using a validated analytical method.	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
Secondary	Neutralizing Antibodies (NAb) Titers for PF-05082566	ADA positive samples were further analyzed for NAb using a validated assay.	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
Secondary	Anti-Drug Antibody (ADA) Titers for Mogamulizumab	Serum samples were assayed for ADA using a validated analytical method.	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
Secondary	Neutralizing Antibodies (NAb) Titers for Mogamulizumab	ADA positive samples were further analyzed for NAb using a validated assay	Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months
Secondary	Number of Participants With Objective Response (OR) and Immune-related Objective Response (irOR)	OR was defined as best overall response (BOR) of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. Immune-related OR (irOR) was defined as immune-related BOR (irBOR) of immune-related CR (irCR) and immune-related PR (irPR) according to immune-related RECIST. CR: Complete disappearance of all target lesions with the exception of nodal disease; PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.	Every 8 weeks up to 24 months
Secondary	Time to Response (TTR) and Immue-related Time to Response (irTTR)-Dose Expansion Portion	TTR was defined, for participants with an OR, as the time from the date of first dose of study treatment to the first documentation of OR (CR or PR), which was subsequently confirmed. irTTR was defined, for participants with an irOR, as the time from the first dose of study treatment to the first documentation of irOR (irCR or irPR) which was subsequently confirmed. CR: Complete disappearance of all target lesions with the exception of nodal disease; PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions.	Every 8 weeks up to 24 months
Secondary	Duration of Response (DR) and Immune-related DR (irDR) -Dose Expansion Portion	DR was defined, for participants with an OR, as the time from first documentation of OR (CR or PR) to the date of first documentation of objective progression disease (PD) or death due to any cause. irDR was defined, for participants with an irOR, as the time from the first documentation of irOR (irCR or irPR) to the date of first documentation of immune-related PD (irPD) (which was subsequently confirmed) or death due to any cause. CR: Complete disappearance of all target lesions with the exception of nodal disease; PR: Greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions; PD: 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.	Every 8 weeks from the first occurrence of CR or PR, until disease progression or death up to 24 months
Secondary	Progression Free Survival (PFS) and Immune-related PFS (irPFS) - Dose Expansion Portion	PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD or death due to any cause, whichever occurred first. irPFS was defined as the time from the first dose of study treatment to the date of first documentation of irPD (which was subsequently confirmed) or death due to any cause, whichever occurred first. PD:20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm.	Every 8 weeks up to 24 months

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