PF-06671008 Dose Escalation Study in Advanced Solid Tumors

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.

Time frame: Baseline through Day 21 (Cycle 1)

Population: All enrolled participants who received at least one dose of study intervention.

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.

Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months

Population: This study was terminated early and Part 2 was not initiated. Data for this outcome measure was not collected.

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.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.

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.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.

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.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.

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.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.

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.

Time frame: C1D1 0 hrs, D15 0 hrs, and C2D1 0 hrs, and D1 0 hrs post additional dosings, up to 24 months

Population: All enrolled participants who received at least one dose of study intervention and had at least one post dose ADA sample analyzed.

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.

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

Population: All randomized participants who received at least 1 dose of study intervention, had measurable disease baseline assessment and at least 1 post baseline assessment or disease progression or death before the first tumor assessment. No participants met the criteria of OR.

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).

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

Population: This study was terminated early and Part 2 was not initiated. Data for this outcome measure were not collected.

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).

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

Population: This study was terminated early and Part 2 was not initiated. Data for this outcome measure were not collected.

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.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.

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.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.

Time for Maximum serum concentration (Tmax) of PF-06671008 was observed directly from data as time of first occurrence.

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

Population: All enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest and who had no major protocol deviations influencing the PK assessment.