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IGF-1R antibody, 20 mg/kg, IV every 3 weeks for up to 1 year

figitumumab

growth hormone antagonist, 10, 20 or 30 mg per day via subcutaneous injection for up to 1 year

pegvisomant

Pfizer CT.gov Call Center

This is a Phase 1 study investigating the safety and tolerability of Figitumumab plus Pegvisomant for treatment of advanced solid tumors.

This study was closed to enrollment on 18 April 2011 due to inability to recruit patients on a timely basis as well as business reasons. Study closure was not related to any safety concerns.

Figitumumab Combined With Pegvisomant For Advanced Solid Tumors

Phase 1 Safety And Tolerability Study Of Figitumumab Combined With Pegvisomant In Patients With Advanced Solid Tumors

Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. AEs were graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 (Grade \[Gr\] 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death). Relatedness to \[study drug\] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category.

DLT was defined as any of the following events occurring during DLT period and considered related to study medication: Grade (Gr) 4 neutropenia lasting \>=7 days, febrile neutropenia (Gr 3 or 4 neutropenia, fever \>=38.5 degrees Celsius, lasting over 24 hours), neutropenic infection (Gr \>=3 neutropenia, infection); Gr 3 or 4 thrombocytopenia associated with bleeding or Gr 4 thrombocytopenia \>=7 days; Gr 3 or 4 lymphopeniab accompanied by an opportunistic infection; other non-hematologic Grade 4 toxicities or symptomatic Gr 3 toxicities that require medical intervention and 14 days to resolve.

The effect of the combined therapy with figitumumab and pegvisomant on circulating concentrations of total IGF-1 was assessed.

Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab from Cycle 2 to the end of treatment.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of figitumumab in cycle 1.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)of figitumumab after Cycle 1

The trough concentration-time profile (AUCtrough) of pegvisomant was to be analyzed by noncompartmental methods.

The effect of combining figitumumab with pegvisomant was analyzed to assess whether pegvisomant reverses figitumumab-induced glucose intolerance at various pegvisomant dose levels. The change in glucose load was assessed by Glucose Tolerance Testing (GTT) at baseline (fasting), during Cycle 1 following administration of figitumumab alone (post load), and near the end of Cycle 2 (post load) following combined therapy with figitumumab and pegvisomant.

Percentage of participants with positive total or neutralizing ADA for figitumumab.

Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST)version 1.1. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST version 1.1. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Figitumumab 20 mg/kg + Pegvisomant 10 mg

Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles (up to total duration of 27 cycles). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily up to total duration of 27 cycles. Each cycle was of 21 days.

Figitumumab 20 mg/kg + Pegvisomant 20 mg

Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 10 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Figitumumab 20 mg/kg +Pegvisomant 10 mg

Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily, up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Total

Age Continuous

Sex: Female, Male

The study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Pfizer ClinicalTrials.gov Call Center

Number of participants with AEs

Number of participants with SAEs

Number of participants with Gr 3 or Gr 4 AEs

Number of participants with Gr 5 AEs

Figitumumab 20mg/kg + Pegvisomant 10 mg

Figitumumab 20 milligram/kilogram (mg/kg) intravenously over 1 to 2.5 hours on Day 1 and 2 of Cycle 1 and on Day 1 of subsequent cycles, up to a maximum of 17 cycles (corresponding to 1 year). Pegvisomant 40 mg subcutaneously on Day 15 of Cycle 1 or Day 1 of Cycle 2 and thereafter pegvisomant 20 mg subcutaneously once daily up to a maximum of 17 cycles (corresponding to 1 year). Each cycle was of 21 days.

Figitumumab 20mg/kg + Pegvisomant 20 mg

Safety analysis set: all enrolled participants who received at least 1 dose of either of the study medications.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Safety analysis set: all enrolled participants who received at least 1 dose of either of the study medications. N=number of participants remained on treatment throughout the required DLT period and included as analyzed for DLT based on the defined DLT evaluability specifications.

Number of Participants With Dose Limiting Toxicities (DLT)

Baseline/Cycle 1 (n = 16, 6)

Cycle 2 (n = 12, 6)

Cycle 3 (n = 6, 5)

Cycle 4 (n = 5, 3)

Cycle 5 (n = 3, 4)

Cycle 6 (n = 2, 2)

Cycle 7 (n = 1, 2)

Cycle 8 (n = 0, 2)

Cycle 9 (n = 0, 2)

Cycle 10 (n = 0, 2)

Cycle 11 (n = 0, 2)

Cycle 12 (n = 0, 2)

Cycle 13 (n = 0, 2)

Cycle 14 (n = 0, 2)

Cycle 15 (n = 0, 2)

Cycle 16 (n = 0, 2)

Cycle 17 (n = 0, 2)

Cycle 18 (n = 0, 2)

Cycle 19 (n = 0, 1)

Cycle 20 (n = 0, 2)

Cycle 21 (n = 0, 2)

Cycle 22 (n = 0, 1)

Cycle 23 (n = 0, 1)

Cycle 24 (n = 0, 1)

Cycle 25 (n = 0, 1)

Cycle 26 (n = 0, 1)

Cycle 27 (n = 0, 0)

Follow-Up (n = 2, 1)

Biomarker analysis set: all enrolled participants who had at least 1 baseline or on-study sample submitted. N=number of participants who were evaluable for IGF-1 Levels at prespecified time points.

Serum Circulating Insulin-like Growth Factor (IGF-1) Levels

PK samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Cycle 1: Maximum Observed Plasma Concentration (Cmax) of Figitumumab

Maximum Observed Plasma Concentration (Cmax) of Figitumumab

Cycle 1: Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab

Plasma Concentration at the Last Quantifiable Time Point (Clast) of Figitumumab

Cycle 1: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Figitumumab

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)of Figitumumab

Area Under the Trough Concentrations (AUCtrough)

Screening (n = 17, 6)

Cycle 1 Day 8 (n = 15, 5)

Cycle 2 Day 15 (n = 4, 5)

Glucose tolerance set: All enrolled participants who started treatment and who had at least one baseline or on-study sample submitted. N=number of participants with analyable data for this outcome measure.

Mean Change in Glucose Levels Between Fasting and Post Glucose Load

ADA samples were not analyzed as the study was terminated prematurely due to lack of operational feasibility and the halt of figitumumab development.

Percentage of Participants Reporting Positive Anti-Drug Antibodies (ADA) Response for Figitumumab

Response-evaluable set: All participants who started Cycle 1 with an adequate baseline tumor assessment and at least 1 follow up tumor assessment.

Spots Global Cancer Trial Database for advanced solid tumors cancer refractory cancer figitumumab pegvisomant