A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors

NCT02222922 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: B76610012014-003296-36
• Study Type: interventional
• Target: 138
• Locations: 2 countries
• Sites: 17

Brief Summary

To assess the safety and tolerability at increasing dose levels of PF-06647020 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Conditions

Neoplasms

Keywords

ADC; PF-06647020; solid tumors; tumors; neoplasm metastasis; TNBC; triple negative breast cancer; NSCLC; non small cell lung cancer; advanced metastatic breast cancer; ovarian cancer; OVCA

Outcome Measures

Primary Outcomes (16)

• Number of Participants With Dose Limiting Toxicities (DLTs) - Q3W Regimen

  A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose or until participant received second infusion if there were treatment delays). (1)Hematologic: including Grade 4 neutropenia lasting \>7 days; Febrile neutropenia; Grade \>=3 neutropenic infection; Grade 4 anemia; Grade \>=3 thrombocytopenia with clinically significant bleeding. (2) Hepatic, including Grade \>=3 serum bilirubin, hepatic transaminase or alkaline phosphatase; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>=3.0 x upper limit of normal (ULN) concurrent with elevation in bilirubin \>=2.0 x ULN; (3) Grade \>=3 non-hematologic, non-hepatic major organ toxicities; delayed by \>2 weeks in receiving the next scheduled cycle due to persisting toxicities attributable to PF-06647020. A participant was on study for at least 21 days to be evaluable for DLT observation, and could be replaced if they terminated study participation earlier than 21 days.

  First Cycle, Day 1 up to Day 21

• Number of Participants With Treatment-Emergent Adverse Events (AEs) - Q3W Regimen (All-Causality)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study medication.

  From the time the participant took the first dose of study medication through the participant's last visit. (approximately 32 months)

• Number of Participants With Treatment-Emergent AEs - Q3W Regimen (Treatment-Related)

  A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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-emergent AEs were those with initial onset or increasing in severity after the first dose of study medication.

  From the time the participant took the first dose of study medication through the participant's last visit. (approximately 32 months)

• Number of Participants With Treatment-Emergent AEs Categorized by Seriousness - Q3W Regimen (All-Causality and Treatment-Related)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study medication. All AEs were graded by the investigator according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.

  From the time the participant took the first dose of study medication through the participant's last visit. (approximately 32 months)

• Number of Participants With Hematology Laboratory Abnormalities (All Cycles) - Q3W Regimen

  Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: absolute neutrophils, lymphopenia, white blood cell, anemia, platelets.

  From baseline to end of treatment (approximately 32 months).

• Number of Participants With Chemistry Laboratory Abnormalities (All Cycles) - Q3W Regimen

  Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: hypokalemia, hypophosphatemia, aspartate aminotransferase, hyperglycemia, alkaline phosphatase, hyponatremia, alanine aminotransferase, hypoalbuminemia, total bilirubin, hypercalcemia, hypomagnesemia , creatinine, gamma glutamyl transferase, hypocalcemia.

  From baseline to end of treatment (approximately 32 months).

• Number of Participants With Urinalysis Laboratory Abnormalities (All Cycles) - Q3W Regimen

  Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above.

  From baseline to end of treatment (approximately 32 months).

• Number of Participants With Coagulation Laboratory Abnormalities (All Cycles) - Q3W Regimen

  Participants who experienced coagulation laboratory test abnormalities were summarized according to worst toxicity grade observed for each coagulation laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with coagulation laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameter: partial thromboplastin time.

  From baseline to end of treatment (approximately 32 months).

• Number of Participants With DLTs - Q2W Regimen

  A DLT was any of the following AEs in the first cycle of treatment (within 28 days of first dose or until participant received second infusion if there were treatment delayed) in the single agent dose escalation. (1)Hematologic: including Grade 4 neutropenia lasting \>7 days; Febrile neutropenia; Grade \>=3 neutropenic infection; Grade 4 thrombocytopenia; treatment delay \>14 days because of hematologic AE; (2) Hepatic: including Grade\>=3 serum bilirubin, hepatic transaminase or alkaline phosphatase; ALT or AST\>=3.0 x ULN concurrent with elevation in bilirubin\>=2.0 x ULN; (3) Grade \>=3 non-hematologic, non-hepatic major organ toxicities; delayed by \>2 weeks in receiving the next scheduled cycle due to persisting toxicities attributable to PF-06647020. Grade \>=3 headache lasting \>48 hours in presence of supportive care. A participant was on study for at least 28 days to be evaluable for DLT observation, and could be replaced if they terminated study participation earlier than 28 days.

  First cycle, Day 1 up to Day 28

• Number of Participants With Treatment-Emergent AEs - Q2W Regimen (All-Causality)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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-emergent AEs were those with initial onset or increasing in severity after the first dose of study medication.

  From the time the participant took the first dose of study medication through the participant's last visit. (approximately 19 months)

• Number of Participants With Treatment-Emergent AEs - Q2W Regimen (Treatment-Related)

  A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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-emergent AEs were those with initial onset or increasing in severity after the first dose of study medication.

  From the time the participant took the first dose of study medication through the participant's last visit. (approximately 19 months)

• Number of Participants With Treatment-Emergent AEs Categorized by Seriousness - Q2W Regimen (All-Causality and Treatment-Related)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study medication. All AEs were graded by the investigator according to the NCI CTCAE version 4.03. Grade 1 AEs are mild AEs; Grade 2 AEs are moderate AEs; Grade 3 AEs are severe AEs, Grade 4 AEs are life-threatening consequences and Grade 5 AEs are deaths related to AEs. Each AE was counted once for the participant in the most severe severity.

  From the time the participant took the first dose of study medication through the participant's last visit. (approximately 19 months)

• Number of Participants With Hematology Laboratory Abnormalities (All Cycles) - Q2W Regimen

  Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: absolute neutrophils, lymphopenia, white blood cell, anemia.

  From baseline to end of treatment (approximately 19 months).

• Number of Participants With Chemistry Laboratory Abnormalities (All Cycles) - Q2W Regimen

  Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: hypokalemia, hyponatremia, hypomagnesemia, hypoalbuminemia, hypocalcemia, hypophosphatemia, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase.

  From baseline to end of treatment (approximately 19 months).

• Number of Participants With Urinalysis Laboratory Abnormalities (All Cycles) - Q2W Regimen

  Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above.

  Baseline and Day 1 of Cycle 1

• Number of Participants With Coagulation Laboratory Abnormalities (All Cycles) - Q2W Regimen

  Participants who experienced coagulation laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03. This outcome measure calculated the number of participants with coagulation laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameter: prothrombin time international normalized ratio.

  From baseline to end of treatment (approximately 19 months).

Secondary Outcomes (70)

• Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) for PF-06647020 - Q3W Regimen

  pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).

• Maximum Observed Serum Concentration (Cmax) for PF-06647020 -Q3W Regimen

  pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).

• Clearance (CL) for PF-06647020 - Q3W Regimen

  pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).

• Volume of Distribution at Steady State (Vss) for PF-06647020 - Q3W Regimen

  pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).

• Terminal Half-Life (t1/2) for PF-06647020 - Q3W Regimen

  pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).

Study Arms (4)

PF-06647020 Q3W

EXPERIMENTAL

Investigational drug infused over 60 minutes once every 21 days.

Drug: PF-06647020 Q3W

Drug-drug interaction (DDI)

EXPERIMENTAL

PF-06647020 combined with fluconazole

Drug: fluconazole

PF-06647020 Q2W

EXPERIMENTAL

Investigational drug infused over 60 minutes once every 14 days (28 day cycle)

Drug: PF-06647020 Q2W

PF-06647020 combined with Avelumab

EXPERIMENTAL

PF-06647020 combined with Avelumab administered by infusion

Drug: PF-06647020 combined with Avelumab

Interventions

PF-06647020 Q3W DRUG

Part 1: PF-06647020 will be administered intravenously every 21 days in cohorts of 2-4 patients starting at a dose of 0.20mg/kg. Increases in dose will continue until MTD is determined. Part 2: Patients with triple negative breast cancer (pre-selected for PTK7 moderately high to high expression), non small cell lung cancer (pre-selected with moderate to high PTK7 expression) and ovarian cancer patients (unselected for PTK7 expression) will be treated at the MTD or Recommended Phase 2 Dose selected in Part 1.

PF-06647020 Q3W

fluconazole DRUG

combination drug used for drug-drug interaction sub-study

Drug-drug interaction (DDI)

PF-06647020 Q2W DRUG

Part 1: PF-06647020 will be administered intravenously every 14 days in cohorts of 2-4 patients starting at a dose of 2.1 mg/kg. Increases in dose will continue until MTD is determined. Part 2: Patients with non-small cell lung cancer (pre-selected for PTK7 moderate to high expression and ovarian cancer patients (unselected for PTK7 expression) will be treated at the MTD or Recommended Phase 2 Dose selected in Part 1.

PF-06647020 Q2W

PF-06647020 combined with Avelumab DRUG

Part 2: Patients with ovarian cancer (unselected for PTK7 expression) will be treated with PF-0664702 plus Avelumab.

PF-06647020 combined with Avelumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of platinum resistant or refractory OVCA having received 2 or fewer prior lines, or recurrent advanced NSCLC having received 3 or fewer prior lines
• Performance Status of 0, 1, or 2
• Adequate bone marrow, kidney, and liver function

You may not qualify if:

• OVCA pts excluded with any of the following: non-epithelial, including malignant mixed mullerian tumors, unresolved bowel obstruction
• Brain metastases requiring steroids
• Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start
• Active and clinically significant bacterial, fungal, or viral infection
• Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
• Performance Status of 0 or 1
• Adequate bone marrow, kidney, and liver function
• Part 2 includes ovarian cancer, target expressing triple negative breast cancer and non small cell lung cancer patients
• OVCA pts excluded with any of the following: non-epithelial, including malignant mixed mullerian tumors, prior radiotherapy to pelvis/abdomen, pts with CA-125 only disease, unresolved bowel obstruction
• Brain metastases requiring steroids
• Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start
• Active and clinically significant bacterial, fungal, or viral infection

Sponsors & Collaborators

• Pfizer: lead

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Scottsdale Healthcare Hospitals DBA HonorHealth

Scottsdale, Arizona, 85258, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Stanford Cancer Center

Stanford, California, 94305, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

START Midwest

Grand Rapids, Michigan, 49503, United States

Location

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

Location

Inova Fairfax Hospital Woodburn GYN Infusion Center

Annandale, Virginia, 22003, United States

Location

Mid Atlantic Gynecologic Oncology and Pelvic Surgery Associates (MAGOPSA)

Annandale, Virginia, 22003, United States

Location

Fairfax Radiological Consultants

Fairfax, Virginia, 22031, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Inova Loudon Hospital

Leesburg, Virginia, 20176, United States

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Related Publications (2)

• Johnson M, El-Khoueiry A, Hafez N, Lakhani N, Mamdani H, Rodon J, Sanborn RE, Garcia-Corbacho J, Boni V, Stroh M, Hannah AL, Wang S, Castro H, Spira A. Phase I, First-in-Human Study of the Probody Therapeutic CX-2029 in Adults with Advanced Solid Tumor Malignancies. Clin Cancer Res. 2021 Aug 15;27(16):4521-4530. doi: 10.1158/1078-0432.CCR-21-0194. Epub 2021 Jun 3.

  PMID: 34083236 DERIVED

• Maitland ML, Sachdev JC, Sharma MR, Moreno V, Boni V, Kummar S, Stringer-Reasor E, Lakhani N, Moreau AR, Xuan D, Li R, Powell EL, Jackson-Fisher A, Bowers M, Alekar S, Xin X, Tolcher AW, Calvo E. First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors. Clin Cancer Res. 2021 Aug 15;27(16):4511-4520. doi: 10.1158/1078-0432.CCR-20-3757. Epub 2021 Jun 3.

  PMID: 34083232 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms

Interventions

Fluconazole; avelumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Breast Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: August 22, 2014
• Study Start: October 17, 2014
• Primary Completion: November 5, 2019
• Study Completion: November 5, 2019
• Last Updated: December 17, 2020
• Results First Posted: December 17, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); US (15)