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The purpose of this study is to evaluate:
The relatively restricted C4.4a expression pattern provides a target for the selective delivery of a cytotoxic drug to C4.4.a-expressing tumor cells by means of a suitable antibody-drug conjugate. The subject population eligible for the current study will be those subjects with advanced malignancies known to express C4.4a, which are refractory to standard therapy or those without standard therapy or actively refusing any treatment, which would be regarded as standard and in whom, in the opinion of the investigator, experimental therapy with BAY1129980 may be beneficial.Depending on the number of dose-escalating steps and the occurrence of DLTs, the planned numbers of subjects could vary.It is expected that up to 90 subjects may participate in the dose-expansion phase of the study and up to 6-9 subjects may particpate in the dose re-esclation phase.The study assessments in the expansion phase of the study are identical to those in the dose-escalation phase.
Amendment # 3 includes changes to DLT criteria (hematological and non-hematological) and allows for frequent follow-up for subjects experiencing drug-related liver toxicity that warrants dose reduction or dose interruptions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lupartumab Amadotin (BAY1129980) | Experimental | Dose escalation with consecutive expansion at MTD (maximum tolerated dose) with BAY1129980. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lupartumab Amadotin (BAY1129980) | Drug | Starting dose is 0.15mg/kg intravenous (I.V.) administration every 21 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose (MTD) | MTD is defined as the maximum dose at which the incidence of DLTs (dose limiting toxicities) during Cycle 1 is below 20%, or the maximum dose administered, whichever is achieved first during dose escalation. | 21 days |
| Number of participants with adverse events as a measure of safety and tolerability | Up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| C4.4a expression levels in tumour tissue as measured by immunohistochemistry (IHC) | Baseline | |
| Tumor response evaluation following RECIST 1.1 criteria | Up to 2 years | |
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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 |
|---|---|---|---|---|---|---|
| La Jolla | California | 92093 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28292941 | Derived | Willuda J, Linden L, Lerchen HG, Kopitz C, Stelte-Ludwig B, Pena C, Lange C, Golfier S, Kneip C, Carrigan PE, Mclean K, Schuhmacher J, von Ahsen O, Muller J, Dittmer F, Beier R, El Sheikh S, Tebbe J, Leder G, Apeler H, Jautelat R, Ziegelbauer K, Kreft B. Preclinical Antitumor Efficacy of BAY 1129980-a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody-Drug Conjugate for the Treatment of Non-Small Cell Lung Cancer. Mol Cancer Ther. 2017 May;16(5):893-904. doi: 10.1158/1535-7163.MCT-16-0474. Epub 2017 Mar 14. |
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| Plasma concentration of BAY1129980 characterized by AUC (0-tlast) |
| 2 years |
| Antidrug and antibody titer | Baseline and up to 2 years |
| Stanford |
| California |
| 94305 |
| United States |
| Aurora | Colorado | 80045 | United States |
| Washington D.C. | District of Columbia | 20007-2197 | United States |
| Gainesville | Georgia | 32610 | United States |
| Westwood | Kansas | 66205 | United States |
| Hackensack | New Jersey | 07601 | United States |
| Buffalo | New York | 14263 | United States |
| New York | New York | United States |
| Durham | North Carolina | 27710 | United States |
| Philadelphia | Pennsylvania | 19104 | United States |
| Nashville | Tennessee | 37203 | United States |
| Dallas | Texas | 75230 | United States |
| Houston | Texas | 77030 | United States |
| Seattle | Washington | 98109-1023 | United States |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
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