Phase Ib Study of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin in Patients With Recurrent Mesothelin-expressing Platinum-resistant Cancer

Study Overview
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Brief Summary
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Anetumab ravtansine is developed for the treatment of patients with recurrent platinum-resistant ovarian cancer. The purpose of the proposed trial is to identify the maximum tolerated dose of anetumab ravtansine that could be safely combined with pegylated liposomal doxorubicin in this indication.

Official Title
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An Open-label Phase Ib Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Maximum Tolerated Dose of Anetumab Ravtansine in Combination With Pegylated Liposomal Doxorubicin 30 mg/m2 Given Every 3 Weeks in Subjects With Mesothelin-expressing Platinum-resistant Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Drug: Anetumab ravtansine (BAY94-9343)
* Drug: Pegylated Liposomal Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with locally invasive or metastatic, epithelial ovarian, fallopian tube, or primary peritoneal cancer Subjects must provide samples of tumor tissue Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Subjects with low-grade ovarian, fallopian tube, or Primary peritoneal cancer Women who are pregnant or breast feeding Subjects who have an active hepatitis B virus or hepatitis C virus infection requiring treatment as defined in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anetumab ravtansine<br>Anetumab ravtansine in combination with pegylated liposomal doxorubicin in subjects with mesothelin-expressing platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancer. Increase/Decrease of Anetumab ravtansine until maximum tolerated dose identified. | Drug: Anetumab ravtansine (BAY94-9343)<br>* Anetumab ravtansine will be administered on Day 1 of every 21-day treatment cycle.<br>Drug: Pegylated Liposomal Doxorubicin<br>* Pegylated liposomal doxoribicin will be administered on Day 1 of every 21-day treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of Anetumab ravtansine in combination with pegylated liposomal doxorubicin when given every three weeks | MTD is defined as the highest dose of anetumab ravtansine administered in combination with pegylated liposomal doxorubicin that can be given such that not more than 1 of 6 subjects at a given dose level experiences a dose-limiting toxicity (DLT). | Up to 6 months, minimum: 1 cycle (=21days) | 
| Incidence of serious and non-serious adverse events (AEs) |  | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (area under the plasma concentration vs. time curve from zero to infinity after single (first) dose) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me) |  | At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1 | 
| AUC(0-tlast) (AUC from time zero to the last data point > lower limit of quantification) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me) |  | At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1 | 
| Cmax (maximum drug concentration in plasma after first dose administration) of Anetumab ravtansine analytes (Antibody drug conjugates, Total Antibody, metabolites DM4, and DM4-Me) |  | At pre-dose, 0.5h, 1h, 1.5h, 2h, 3h, 5h, 8h, 24h, 48h, 168h, 336h and 504h post-dose, beginning on day 1 of cycle 1 | 
| AUC of total pegylated liposomal doxorubicin |  | At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1 | 
| AUC(0-tlast) of total pegylated liposomal doxorubicin |  | At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose , beginning on day 1 of cycle 1 | 
| Cmax of total pegylated liposomal doxorubicin |  | At pre-dose, 0.5h, 1h, 2h, 3h, 6h, 8h, 22h, 46h, and 166h post-dose, beginning on day 1 of cycle 1 | 
| Incidence of patients with CR, PR, SD or PD according to RECIST 1.1 | CR (complete response) PR (partial response) SD (stable disease) PD (progressive disease) | Up to 17 months or until discontinuation of study, whichever comes first | 
| Incidence of positive anti-drug antibody titer |  | Up to 17 months or until discontinuation of study, whichever comes first | 
| Incidence of positive neutralizing antibody titer |  | Up to 17 months or until discontinuation of study, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesothelin-expressing platinum-resistant cancer