Clinical trial NCT02222922: A Study Of PF-06647020 For Adult Patients With Advanced Solid Tumors
Official title: A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647020 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-08-22
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

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.


Eligibility criteria: Q2W Inclusion Criteria:

* 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

Q2W Exclusion Criteria:

* 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

Q3W Inclusion Criteria:

* 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

Q3W Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs) - Q3W Regimen
timeFrame: First Cycle, Day 1 up to Day 21
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) - Q3W Regimen (All-Causality)
timeFrame: From the time the participant took the first dose of study medication through the participant's last visit. (approximately 32 months)
measure: Number of Participants With Treatment-Emergent AEs - Q3W Regimen (Treatment-Related)
timeFrame: From the time the participant took the first dose of study medication through the participant's last visit. (approximately 32 months)
measure: Number of Participants With Treatment-Emergent AEs Categorized by Seriousness - Q3W Regimen (All-Causality and Treatment-Related)
timeFrame: From the time the participant took the first dose of study medication through the participant's last visit. (approximately 32 months)
measure: Number of Participants With Hematology Laboratory Abnormalities (All Cycles) - Q3W Regimen
timeFrame: From baseline to end of treatment (approximately 32 months).
measure: Number of Participants With Chemistry Laboratory Abnormalities (All Cycles) - Q3W Regimen
timeFrame: From baseline to end of treatment (approximately 32 months).
measure: Number of Participants With Urinalysis Laboratory Abnormalities (All Cycles) - Q3W Regimen
timeFrame: From baseline to end of treatment (approximately 32 months).
measure: Number of Participants With Coagulation Laboratory Abnormalities (All Cycles) - Q3W Regimen
timeFrame: From baseline to end of treatment (approximately 32 months).
measure: Number of Participants With DLTs - Q2W Regimen
timeFrame: First cycle, Day 1 up to Day 28
measure: Number of Participants With Treatment-Emergent AEs - Q2W Regimen (All-Causality)
timeFrame: From the time the participant took the first dose of study medication through the participant's last visit. (approximately 19 months)
measure: Number of Participants With Treatment-Emergent AEs - Q2W Regimen (Treatment-Related)
timeFrame: From the time the participant took the first dose of study medication through the participant's last visit. (approximately 19 months)
measure: Number of Participants With Treatment-Emergent AEs Categorized by Seriousness - Q2W Regimen (All-Causality and Treatment-Related)
timeFrame: From the time the participant took the first dose of study medication through the participant's last visit. (approximately 19 months)
measure: Number of Participants With Hematology Laboratory Abnormalities (All Cycles) - Q2W Regimen
timeFrame: From baseline to end of treatment (approximately 19 months).
measure: Number of Participants With Chemistry Laboratory Abnormalities (All Cycles) - Q2W Regimen
timeFrame: From baseline to end of treatment (approximately 19 months).
measure: Number of Participants With Urinalysis Laboratory Abnormalities (All Cycles) - Q2W Regimen
timeFrame: Baseline and Day 1 of Cycle 1
measure: Number of Participants With Coagulation Laboratory Abnormalities (All Cycles) - Q2W Regimen
timeFrame: From baseline to end of treatment (approximately 19 months).
Secondary outcomes:
measure: Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Maximum Observed Serum Concentration (Cmax) for PF-06647020 -Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Clearance (CL) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Volume of Distribution at Steady State (Vss) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Terminal Half-Life (t1/2) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Observed Accumulation Ratio (Rac) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4 (21 days cycle).
measure: Time for Cmax (Tmax) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Area Under the Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) for PF-06647020 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: AUCtau for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Cmax for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: t1/2 for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Rac for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4 (21 days cycle).
measure: Tmax for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: AUClast for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: AUCinf for PF-06380101 - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: AUCtau for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Cmax for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: t1/2 for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Rac for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 4 (21 days cycle).
measure: Tmax for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: AUClast for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: AUCinf for hu6M024 mAb - Q3W Regimen
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 4 (21 days cycle).
measure: Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) of PF-06647020 - Q3W Regimen
timeFrame: Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (approximately 31 months).
measure: Percentage of Participants With Objective Response - Q3W Regimen
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months).
measure: Duration of Response - Q3W Regimen
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months).
measure: Disease Control Rate - Q3W Regimen
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months).
measure: Time to Progression - Q3W Regimen
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months).
measure: Progression Free Survival - Q3W Regimen
timeFrame: Baseline, every 6 weeks from the start of treatment until disease progression, death or withdrawal from treatment (approximately 32 months).
measure: Dose Normalized AUCinf [AUCinf(dn)] for PF-06647020 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: Dose Normalized AUClast [AUClast(dn)] for PF-06647020 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: Dose Normalized AUCtau [AUCtau(dn)] for PF-06647020 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: Dose Normalized Cmax [Cmax(dn)] for PF-06647020 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUCinf(dn) for PF-06380101 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUClast(dn) for PF-06380101 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUCtau(dn) for PF-06380101 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: Cmax(dn) for PF-06380101 [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUCinf(dn) for hu6M024 mAb [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUClast(dn) for hu6M024 mAb [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUCtau(dn) for hu6M024 mAb [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: Cmax(dn) for hu6M024 mAb [DDI Sub-Study]
timeFrame: pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose for Cycle 1 and Cycle 2 (21 days cycle).
measure: AUCtau for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Cmax for PF-06647020 -Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Vss for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: CL for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: t1/2 for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Rac for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 3 (28 days cycle).
measure: Tmax for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUClast for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUCinf for PF-06647020 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUCtau for PF-06380101 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Cmax for PF-06380101 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: t1/2 for PF-06380101 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Rac for PF-06380101 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 3 (28 days cycle).
measure: Tmax for PF-06380101 - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUClast for PF-06380101- Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUCinf for PF-06380101- Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUCtau for hu6M024 mAb- Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Cmax for hu6M024 mAb -Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: t1/2 for hu6M024 mAb - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Rac for hu6M024 mAb - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4 hours post-dose on Day 1 of Cycle 1 and Day 1 of Cycle 3 (28 days cycle).
measure: Tmax for hu6M024 mAb - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUClast for hu6M024 mAb - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: AUCinf for hu6M024 mAb - Q2W Regimen
timeFrame: pre-dose, end of infusion, 4, 24, 72, 168 hours post-dose, Day 15 (pre-dose, end of infusion) for Cycle 1 and Cycle 3 (28 days cycle).
measure: Number of Participants With ADA and NAb of PF-06647020 - Q2W Regimen
timeFrame: 2 hours before the first dose up to 30 days after the last dose (approximately 18 months).
measure: Percentage of Participants With Objective Response - Q2W Regimen
timeFrame: Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months).
measure: Duration of Response - Q2W Regimen
timeFrame: Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months).
measure: Disease Control Rate - Q2W Regimen
timeFrame: Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months).
measure: Time to Progression - Q2W Regimen
timeFrame: Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months).
measure: Progression Free Survival - Q2W Regimen
timeFrame: Baseline, every 8 weeks from the start of study treatment until disease progression, death or withdrawal from treatment (approximately 19 months).
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals DBA HonorHealth
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis Comprehensive Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital and Clinics
state: California
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
city: Annandale
country: United States
facility: Inova Fairfax Hospital Woodburn GYN Infusion Center
state: Virginia
city: Annandale
country: United States
facility: Mid Atlantic Gynecologic Oncology and Pelvic Surgery Associates (MAGOPSA)
state: Virginia
city: Fairfax
country: United States
facility: Fairfax Radiological Consultants
state: Virginia
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Leesburg
country: United States
facility: Inova Loudon Hospital
state: Virginia
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.