NCT02659631 · REGISTRY CONDITION SEARCH

PF-06671008 Dose Escalation Study in Advanced Solid Tumors

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2020-05-06

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1

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outcome · POSTED

Number of Participants With Objective Response (OR) - Part 2

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outcome · POSTED

Maximum Serum Concentration (Cmax) of PF-06671008

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outcome · POSTED

Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008

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outcome · POSTED

Terminal Elimination Half-life (t1/2) of PF-06671008

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outcome · POSTED

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008

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outcome · POSTED

Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008

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outcome · POSTED

Systemic Clearance (CL) of PF-06671008

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outcome · POSTED

Apparent Clearance (CL/F) of PF-06671008

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outcome · POSTED

Number of Participants With OR - Part 1

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outcome · POSTED

Number of Participants With Progression Free Survival (PFS) - Part 2

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outcome · POSTED

Number of Participants With Overall Survival (OS) - Part 2

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outcome · POSTED

Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

intervention Names
Drug: PF-06671008
label
PF-06671008
type
EXPERIMENTAL

interventions

arm Group Labels
PF-06671008
description
Dose Escalation Phase - Part 1
name
PF-06671008
type
DRUG
arm Group Labels
PF-06671008
description
Dose Expansion Phase - Part 2
name
PF-06671008
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 28
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
DLT was defined as any of the following adverse events occurring in the first cycle of treatment (21 days after the first dose): a) Hematologic: Febrile neutropenia defined as an absolute neutrophil count (ANC) \<1.0 x 10\^9/L with a single temperature of \>38.3°C, or 101°F, or a sustained temperature of \>=38°C, or 100.4°F, for more than one hour; b) Non-hematologic: Delay by more than 2 weeks in receiving the next scheduled dose due to persisting treatment related toxicities; c) Any grade 3 or 4 clinically-relevant hematologic or non-hematologic toxicity.
measure
Number of Participants With Dose-Limiting Toxicities (DLTs) - Part 1
time Frame
Baseline through Day 21 (Cycle 1)
description
Number of participants with OR based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
measure
Number of Participants With Objective Response (OR) - Part 2
time Frame
Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months

secondary Outcomes

description
Maximum serum concentration (Cmax) of PF-06671008 was observed directly from data. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
measure
Maximum Serum Concentration (Cmax) of PF-06671008
time Frame
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
description
Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence.
measure
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-06671008
time Frame
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
description
Terminal elimination half-life (t1/2) of PF-06671008 was calculated as ln(2)/kel, where 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. Arithmetic mean was not calculated if fewer than 3 participants had reportable parameter values.
measure
Terminal Elimination Half-life (t1/2) of PF-06671008
time Frame
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
description
Tau refers to the dosing interval, which was 1 week. Area under the concentration-time profile from time 0 to time tau (AUCtau) was determined using linear/log trapezoidal method. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
measure
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06671008
time Frame
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
description
AUCinf was calculated as AUClast +(Clast\*/kel), where AUClast is area under the serum concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis, kel is 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. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
measure
Area Under the Curve From Time 0 Extrapolated to Infinity Time (AUCinf) of PF-06671008
time Frame
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
description
Systemic Clearance (CL) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to IV arms. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
measure
Systemic Clearance (CL) of PF-06671008
time Frame
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
description
Apparent Clearance (CL/F) was calculated as dose/AUCinf, where AUCinf was area under the serum concentration-time profile from time 0 extrapolated to infinite time. This outcome measure only applies to SC arm. Geometric mean was not calculated if fewer than 3 participants had reportable parameter values.
measure
Apparent Clearance (CL/F) of PF-06671008
time Frame
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
description
Number of participants with OR based on assessment of CR or PR according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
measure
Number of Participants With OR - Part 1
time Frame
Baseline and every 6 weeks for the first 6 months, then every 12 weeks until disease progression, unacceptable toxicity, or up to 24 months
description
The period from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was "Death").
measure
Number of Participants With Progression Free Survival (PFS) - Part 2
time Frame
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
description
The period from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death).
measure
Number of Participants With Overall Survival (OS) - Part 2
time Frame
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
description
ADA against PF-06671008 in human serum samples was determined following a tiered approach using screening, confirmation, and titer/quantification by semi-quantitative enzyme linked immunosorbent assay (ELISA). Endpoint titer \>=1.18 was considered positive.
measure
Number of Participants With Anti Drug Antibodies (ADA) and Neutralizing Antibodies (NAb) Against PF-06671008
time Frame
C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months

Full study description

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.

Source references

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.
pmid
35493516
type
DERIVED