Phase I, Dose-escalation Trial of BAY1187982 in Subjects With Advanced Solid Tumors Known to Express Fibroblast Growth Factor Receptor 2 (FGFR2)

NCT02368951 | Terminated Phase 1 FDA Drug

• 1 other identifier: 16897
• Study Type: interventional
• Target: 20
• Locations: 3 countries
• Sites: 13

Brief Summary

To evaluate the safety, tolerability, maximum tolerated dose, pharmacokinetics, and pharmacodynamics of the anti-FGFR2 antibody drug conjugate BAY1187982 in subjects with advanced solid tumors known to express fibroblast growth factor receptor 2 (FGFR2)

Conditions

Medical Oncology

Keywords

Phase 1; Solid Tumors; FGFR2; Antibody drug conjugate

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose(MTD)

  The MTD is defined as the maximum dose at which the incidence of DLTs during Cycle 1 is below 20%, or the maximum dose administered, whichever is achieved first during dose escalation

  Up to 2 years

• Number of subjects with adverse events as a measure of safety and tolerability

  Up to 2 years

• Number of subjects with serious adverse events as a measure of safety and tolerability

  Up to 2 years

Secondary Outcomes (12)

• Cmax (maximum observed drug concentration in measured matrix after single dose administration)

  Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion

• AUC(0-tlast) AUC from time 0 to the last data point >LLOQ

  Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion

• AUC)0-504 (AUC from zero to 504 hours post infusion)

  Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion

• AUC (area under the concentration vs. time curve from zero to infinity after single (first)

  Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion

• Cmax,md (maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval)

  Cycles 1 and 3, Day 1: pre-dose, end of infusion, Day 2, Day 3, Day 5, Day 8, and Day 15.Cycles 2 and 4: Day 1: pre-dose.Cycle 5 Day 1 and every odd cycles after: pre-dose and end of infusion

Study Arms (1)

BAY1187982

EXPERIMENTAL

Dose-escalation phase: Approximately 30 subjects will participate in the dose-escalation phase The total number of subjects will depend on the number of cohorts necessary to identify the MTD. MTD expansion phase: Once the MTD has been determined, two expansion cohorts in FGFR2 expressing indications are planned: Cohort 1: Triple negative breast cancer (TNBC). This cohort will enroll 80 subjects (N=40 with low to moderate FGFR2 expression and N=40 with high FGFR2 expression) Cohort 2: Other indications expressing FGFR2. This cohort 40 subjects will be enrolled.

Drug: BAY1187982

Interventions

BAY1187982 DRUG

A dose of 0.1 mg BAY 1187982 per kilogram (kg) body weight (BW) was chosen as the starting dose based on toxicology data. The investigational drug will be administered as a 1-hour IV infusion once every 21 days at the trial site (Day 1 of each 21-day Cycle). The maximum possible dose escalation will be 2-fold and not more than 0.5 mg/kg BW until maximum tolerated dose is selected

BAY1187982

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must be \>/= 18 years at the first screening examination / visit
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Subjects with advanced, histologically or cytologically confirmed solid tumors described to express fibroblast growth factor receptor 2 (FGFR2) that are refractory to any standard therapy
• For maximum tolerated dose (MTD) Dose Expansion: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer who had undergone within 4 lines of systemic anti-cancer treatment and not eligible for standard therapy anymore.
• Subjects need to have evaluable disease (measurable or not measurable).
• Women of childbearing potential must have a negative pregnancy test performed within 7 days prior to the start of treatment

You may not qualify if:

• History of allergic reactions to monoclonal antibody therapy (or excipients in the formulation)
• Anti-cancer chemotherapy, experimental cancer therapy including clinical trial, or cancer immunotherapy within 4 weeks prior to the first dose of the investigational drug.
• Toxic effects of previous anti-cancer chemotherapy, experimental cancer therapy, or cancer immunotherapy have not normalized.
• History of symptomatic metastatic brain or meningeal tumors unless the subject is longer than 3 months from the end of definitive therapy before the first dose of the investigational drug and has clinically or radiologically no evidence of tumor growth.
• History of clinically significant cardiac disease
• Congenital coagulation abnormalities
• Subjects who are pregnant or are breast-feeding

Sponsors & Collaborators

• Bayer: lead

Study Sites (13)

Unknown Facility

San Francisco, California, 94115, United States

Location

Unknown Facility

Santa Monica, California, 90404-1200, United States

Location

Unknown Facility

New Haven, Connecticut, 06520, United States

Location

Unknown Facility

Chicago, Illinois, 60611, United States

Location

Unknown Facility

Baltimore, Maryland, 21231, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

Nashville, Tennessee, 37232, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

Seattle, Washington, 98109-1023, United States

Location

Unknown Facility

Singapore, 169610, Singapore

Location

Unknown Facility

Seoul, 03080, South Korea

Location

Unknown Facility

Seoul, 138-736, South Korea

Location

Related Publications (1)

• Kim SB, Meric-Bernstam F, Kalyan A, Babich A, Liu R, Tanigawa T, Sommer A, Osada M, Reetz F, Laurent D, Wittemer-Rump S, Berlin J. First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer. Target Oncol. 2019 Oct;14(5):591-601. doi: 10.1007/s11523-019-00670-4.

  PMID: 31502117 DERIVED

MeSH Terms

Interventions

aprutumab ixadotin

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2015
• First Posted: February 23, 2015
• Study Start: March 24, 2015
• Primary Completion: July 27, 2016
• Study Completion: July 27, 2016
• Last Updated: July 12, 2017

Record last verified: 2017-07

Locations

SG (1); KR (2); US (10)