The purpose of this study is to evaluate the safety and tolerability of BAX69 monotherapy given either as intraperitoneal (IP) infusion (Single-Route Arm); or as IP infusion after intravenous (IV) infusion (IV+IP) (Double-Route Arm), and to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) for each Arm separately, in subjects with refractory ovarian cancer and recurrent malignant ascites. In both Arms, the plasma pharmacokinetics (PK) of BAX69 will be characterized, and pharmacodynamics (PD) markers will be explored in plasma and ascites. Two expansion cohorts will further assess the tolerability of the RP2D and explore clinical signs of efficacy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Intraperitoneal (IP) only
Intravenous (IV) infusion + intraperitoneal (IP) infusion
University of Miami Miller School of Medicine
Miami, Florida, United States
Georgia Regents University
Augusta, Georgia, United States
Women's Health Specialists
Silver Spring, Maryland, United States
Montefiore Medical Center
The Bronx, New York, United States
Stephenson Cancer Center at The University of Oklahoma
Oklahoma City, Oklahoma, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
The Occurrence of Dose-limiting Toxicity (DLT)
DLT is defined as any drug related treatment-emergent adverse event that occurs during the 28-day period after the first dose of Imalumab and that meets any of these criteria: - Any ≥ grade 3 non-hematologic toxicity assessed by the investigator as related to study drug (except: single lab value out of normal range not necessarily translating or considered a feature of clinical diagnosis requiring an intervention per investigator's interpretation and resolves to ≤ Grade 2 with adequate measure in 7 days; Transient grade 3 elevations of hepatic transaminases in the absence of simultaneous increase in serum bilirubin; Alopecia) - Any toxicity resulted in dose delay for ≥14 days - Any grade 4 hematologic toxicity (except lymphopenia) - Grade 3 febrile neutropenia - Grade 3 thrombocytopenia associated with bleeding - Any life-threatening complication/abnormality not covered in the NCICTCAE v4.03
Time frame: 4 weeks
The Ratio of Puncture Free Survival (PuFS) Over Puncture-free Interval at Baseline
PuFS is defined as the time from the last dose of Imalumab to the first therapeutic paracentesis after that, or death, whichever occurs first. Puncture-free interval at baseline is calculated as the time between the last 2 therapeutic paracenteses immediately before the first dose of Imalubmab.
Time frame: 4 weeks
Ratio of Time to First Paracentesis Post-treatment Over Puncture-free Interval at Baseline
Time to first paracentesis post-treatment is calculated as the time between the last dose of Imalumab to subsequent first therapeutic paracentesis.
Time frame: 4 weeks
Change in Ascites Volume Per Unit Time With Treatment
The volume of ascites from the last dose of Imalumab to the first post-treatment paracentesis per unit time will be compared to the volume of the last pre-treatment paracentesis per unit time. At each paracentesis, the volume of fluid that can be removed safely (measured by ultrasound-guided paracentesis) to achieve close to dryness should be withdrawn, measured, and documented.
Time frame: Up to 4 weeks
Changes in Ascites-related Symptoms
Ascites related symptoms: anorexia, nausea, early satiety, vomiting, abdominal pain, abdominal swelling, dyspnea, fatigue, swollen ankles, heartburn
Time frame: Baseline, weekly during the treatment period, and every 2 weeks during the safety follow-up period, up to approximately 6 months)
Occurrence of Serious Adverse Events (SAEs) and/or Treatment-emergent Adverse Events (TEAEs), Regardless of Causality or Relationship to Study Drug
Time frame: Throughout the study period of approximately 22 months
Occurrence of Binding and/or Neutralizing Anti-imalumab (BAX69) Antibodies Following Treatment With Imalumab (BAX69)
Time frame: Throughout the study period of approximately 22 months
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Maximum Observed Concentration (Cmax)
Time frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Minimum Observed Concentration (Cmin)
Time frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Area Under the Concentration vs Time Curve (AUC)
Time frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Half-life (t1/2)
Time frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Apparent Systemic Clearance (CL)
Time frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Imalumab (BAX69) Plasma Pharmacokinetic (PK) Parameter: Volume of Distribution (V)
Time frame: Predose; and post-dose at 1.5, 4, 8, 24, and 72 hours
Quality of Life (QoL) Measure - European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Questionnaire
QoL will be assessed using EORTC QLQ-C30.
Time frame: Weekly from the baseline visit to the last week of safety follow-up (8 weeks or longer, if additional treatment will be implemented)
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