Clinical trial NCT02659631: PF-06671008 Dose Escalation Study in Advanced Solid Tumors
Official title: A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06671008 IN PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Keywords: P-cadherin
PF-06671008
solid tumors
lung cancer
breast cancer
colorectal cancer
NSCLC
TNBC
CRC
neoplasms
Triple negative breast cancer
Non-small cell lung cancer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-01-20
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06671008 in patients with advanced solid tumors with the potential to have P-cadherin expression. The study will then expand to look at the selected dose in patients with P-cadherin expressing TNBC, CRC or NSCLC.


Eligibility criteria: Key Inclusion Criteria

* Diagnosis of tumor type with the potential to have P-cadherin expression that is resistant to standard therapy or for which no standard therapy is available
* Performance status of 0 or 1
* Adequate bone marrow, kidney and liver function

Key Exclusion Criteria

* Known CNS disease including, but not limited to, metastases
* Current or history of seizure disorder
* History of or active autoimmune disorders
* Active bacterial, fungal or viral infection
* Major surgery, anti-cancer therapy, or radiation therapy within 4 weeks of study treatment
* Requirement for systemic immune suppressive medication
* Grade 2 or greater peripheral neuropathy

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1
timeFrame: Baseline through Day 21 (Cycle 1)
measure: Number of Participants With Objective Response (OR) - Part 2
timeFrame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Terminal Elimination Half-life (t1/2) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Systemic Clearance (CL) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Apparent Clearance (CL/F) of PF-06671008
timeFrame: C1D1 0, 1, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose, C2D1 0, 2, 4, 8, 24, 48, 72 and 96 hrs post-dose
measure: Number of Participants With OR - Part 1
timeFrame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months
measure: Number of Participants With Progression Free Survival (PFS) - Part 2
timeFrame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months
measure: Number of Participants With Overall Survival (OS) - Part 2
timeFrame: Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression or unacceptable toxicity, or up to 24 months
measure: Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008
timeFrame: C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months
Other outcomes:
Locations:
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center - Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center- Clinical Trials Office
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center Rockefeller Outpatient Pavillion
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Houston
country: United States
facility: The University of Texas - M.D. Anderson Cancer Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Harding JJ, Garrido-Laguna I, Chen X, Basu C, Dowlati A, Forgie A, Hooper AT, Kamperschroer C, Max SI, Moreau A, Shannon M, Wong GY, Hong DS. A Phase 1 Dose-Escalation Study of PF-06671008, a Bispecific T-Cell-Engaging Therapy Targeting P-Cadherin in Patients With Advanced Solid Tumors. Front Immunol. 2022 Apr 14;13:845417. doi: 10.3389/fimmu.2022.845417. eCollection 2022.