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

• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Medical Oncology	Drug: BAY1187982	Phase 1

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	20 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	An Open-label,Phase I, Dose-escalation Trial to Evaluate the Safety, Tolerability, Maximum Tolerated Dose, Pharmacokinetic, and Pharmacodynamics of the Anti-FGFR2 Antibody Drug Conjugate BAY1187982 in Subjects With Advanced Solid Tumors Known to Express FGFR2.
Actual Study Start Date :	March 24, 2015
Actual Primary Completion Date :	July 27, 2016
Actual Study Completion Date :	July 27, 2016

Arms and Interventions

Arm

Intervention/treatment

Experimental: BAY1187982; 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; 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

Outcome Measures

Primary Outcome Measures :

1. Maximum tolerated dose(MTD) [ Time Frame: Up to 2 years ]
   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
2. Number of subjects with adverse events as a measure of safety and tolerability [ Time Frame: Up to 2 years ]
3. Number of subjects with serious adverse events as a measure of safety and tolerability [ Time Frame: Up to 2 years ]

Secondary Outcome Measures :

1. Cmax (maximum observed drug concentration in measured matrix after single dose administration) [ Time Frame: 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 ]
2. AUC(0-tlast) AUC from time 0 to the last data point >LLOQ [ Time Frame: 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 ]
3. AUC)0-504 (AUC from zero to 504 hours post infusion) [ Time Frame: 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 ]
4. AUC (area under the concentration vs. time curve from zero to infinity after single (first) [ Time Frame: 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 ]
5. Cmax,md (maximum observed drug concentration in measured matrix after multiple dose administration during a dosage interval) [ Time Frame: 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 ]
6. AUC(0-tlast)md (AUC from time 0 to the last data point >LLOQ after multiple dosing) [ Time Frame: 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 ]
7. AUC(0-504)md [ Time Frame: 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 ]
8. FGFR2 levels in tumor tissue sample [ Time Frame: Screening ]
9. CK18 levels in tumor tissue sample [ Time Frame: Screening, 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 and end of infusion. ]
10. Nucleosome level in plasma [ Time Frame: Screening, 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 and end of infusion. ]
11. Development of anti-drug antibodies (ADAs) in plasma as an indicator of immunogenicity [ Time Frame: Cycle 1: Day 1: before infusion (pre-dose), Day 8 ]
12. Tumor response [ Time Frame: Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.) ]

Eligibility Criteria

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

Layout table for location information

United States, California
San Francisco, California, United States, 94115
Santa Monica, California, United States, 90404-1200
United States, Connecticut
New Haven, Connecticut, United States, 06520
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, New York
New York, New York, United States, 10016
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Texas
Houston, Texas, United States, 77030
United States, Washington
Seattle, Washington, United States, 98109-1023
Korea, Republic of
Seoul, Korea, Republic of, 03080
Seoul, Korea, Republic of, 138-736
Singapore
Singapore, Singapore, 169610

Sponsors and Collaborators

Bayer

Investigators

Layout table for investigator information

Study Director:	Bayer Study Director	Bayer

More Information

Additional Information:

Click here and search for drug information provided by the FDA.  Click here and search for information on any recalls, market or product safety alerts by the FDA which might have occurred with this product.  Click here to find results for studies related to Bayer products. 

Layout table for additonal information

Responsible Party:	Bayer
ClinicalTrials.gov Identifier:	NCT02368951 History of Changes
Other Study ID Numbers:	16897
First Posted:	February 23, 2015
Last Update Posted:	July 12, 2017
Last Verified:	July 2017

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Bayer:

Phase 1; Solid Tumors; FGFR2; Antibody drug conjugate

Additional relevant MeSH terms:

Layout table for MeSH terms

Immunoconjugates; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs