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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)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| San Francisco | California | 94115 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31502117 | Derived | 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. |
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|
| 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 |
| AUC(0-tlast)md (AUC from time 0 to the last data point >LLOQ after multiple dosing) | 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)md | 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 |
| FGFR2 levels in tumor tissue sample | Screening |
| CK18 levels in tumor tissue sample | 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. |
| Nucleosome level in plasma | 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. |
| Development of anti-drug antibodies (ADAs) in plasma as an indicator of immunogenicity | Cycle 1: Day 1: before infusion (pre-dose), Day 8 |
| Tumor response | Screening, Day 15 (± 7 days) of Cycle 2 and every even subsequent Cycle (i.e. Cycles 2, 4, 6, 8, etc.) |
| Santa Monica |
| California |
| 90404-1200 |
| United States |
| New Haven | Connecticut | 06520 | United States |
| Chicago | Illinois | 60611 | United States |
| Baltimore | Maryland | 21231 | United States |
| St Louis | Missouri | 63110 | United States |
| New York | New York | 10016 | United States |
| Nashville | Tennessee | 37232 | United States |
| Houston | Texas | 77030 | United States |
| Seattle | Washington | 98109-1023 | United States |
| Singapore | 169610 | Singapore |
| Seoul | 03080 | South Korea |
| Seoul | 138-736 | South Korea |
| ID | Term |
|---|---|
| C000621819 | aprutumab ixadotin |
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