A Study of Tilvestamab (BGB149) in Relapsed, Platinum-resistant, High-grade Serous Ovarian Cancer (HGSOC) Participants

Study Overview
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Brief Summary
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The primary purpose is to assess the safety and tolerability of tilvestamab following IV administration of multiple doses to participants with HGSOC who have been treated with at least 1 complete course of platinum-based chemotherapy and whose disease has relapsed with platinum resistance ([PRR]-HGSOC) and to determine the plasma pharmacokinetics (PK) exposure by comprehensive profiling (at single dose and steady-state) of multiple ascending doses of tilvestamab.

Official Title
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Phase 1b, Multicentre, Multiple Ascending Dose, Safety, Pharmacokinetic, and Pharmacodynamic Study of Tilvestamab (BGB149) in Relapsed, Platinum-resistant, High-grade Serous Ovarian Cancer (HGSOC) Patients

Conditions
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Ovarian Neoplasms

Intervention / Treatment
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* Biological: Tilvestamab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females of non-childbearing potential at the time of provision of informed consent Ability to understand and provide written confirmation of informed consent after reading study information, discussion with the investigator, and adequate time to decide on participation Consents to storage of study-related samples and data for exploratory use Histologically confirmed HGSOC Platinum-resistant relapsed disease; defined as progressive disease based on imaging within <= 6 months from completion of most recent regimen Exclusion Criteria: Primary platinum-refractory disease (ie, progression during the first platinum regimen or within 4 weeks of completion of the first platinum regimen) with rapid progression and life-threatening disease manifestation Life expectancy < 6 months Concurrent anticancer therapy Participants who are breastfeeding Known uncontrolled central nervous system metastases. Participants without known brain metastases do not require radiological imaging prior to enrolment

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tilvestamab<br>Participants will receive tilvestamab at a low starting dose level (Cohort A) given via intravenous (IV) infusion every 2 weeks. Dose escalations to subsequent cohorts (Cohort B and Cohort C) will be decided by the Protocol Steering Committee (PSC) after review of all Cycle 1 (28 days cycle) safety and pharmacokinetics (PK) data up to Cycle 1 Day 22 for all participants in the ongoing cohort. | Biological: Tilvestamab<br>* Tilvestamab will be administered as IV infusion.<br>* Other names: BGB149;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse events (AEs) and Serious AEs (SAEs) | An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at Screening, worsens during the study, regardless of the suspected cause of the event. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to 2.5 years | 
| Number of Participants with Laboratory Abnormalities | Number of participants with laboratory (haematology, coagulation, clinical chemistry, serum inflammatory cytokine profile, and urinalysis) abnormalities will be reported. | Up to 2.5 years | 
| Number of Participants with Vital Sign Abnormalities | Number of participants with vital sign (supine blood pressure [BP], heart rate, oral temperature, and respiratory rate) abnormalities will be reported. | Up to 2.5 years | 
| Number of Participants with Electrocardiogram (ECG) Abnormalities | Number of participants with resting triplicate 12-lead ECG abnormalities will be reported. | Up to 2.5 years | 
| Number of Participants with Physical Examinations Abnormalities | Number of participants with physical examinations abnormalities will be reported. | Up to 2.5 years | 
| Number of Participants with Concomitant Medication Use | Number of participants with concomitant medication use will be reported. | Up to 2.5 years | 
| Maximum Concentration (Cmax) | Cmax will be determined directly from the concentration-time profile. | Up to 140 days | 
| Time to Cmax (Tmax) | Time to Cmax will be determined directly from the concentration-time profile. | Up to 140 days | 
| Area Under the Concentration-time Curve (AUC) From Predose (Time 0) to the end of the Dosing Period (AUC0-tau) | AUC0-tau will be calculated using the linear-log trapezoidal rule. | Up to 140 days | 
| AUC From Predose (Time 0) to the Time of the Last Quantifiable Concentration (AUClast) | AUClast will be calculated using the linear-log trapezoidal rule. | Up to 140 days | 
| AUC From Predose (Time 0) to 168 Hours Postdose (AUC0-168 ) | AUC0-168 is AUC from predose (time 0) to 168 hours postdose. | Predose up to 168 hours postdose | 
| Terminal Elimination Rate Constant (Lambda[z]) | Lambda[z] will be determined by selection of at least 3 data points on the terminal phase of the concentration-time curve. | Up to 140 days | 
| Terminal Elimination Half-life | Terminal elimination half-life calculated as: ln2/Lambda[z] | Up to 140 days | 
| Total body clearance (CL) | CL is defined as total body clearance. | Up to 140 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Anti-drug Antibodies (ADAs) | Number of participants with ADAs will be reported. | Up to 2.5 years | 
| Number of Participants with Neutralizing Antibodies (NAbs) | Number of participants with NAbs will be reported. | Up to 2.5 years |