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
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- BerGenBio ASA
- Enrollment
- 16
- Locations
- 9
- Primary Endpoint
- Terminal Elimination Rate Constant (Lambda[z])
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Tilvestamab
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.
Intervention: Tilvestamab (Biological)
Outcomes
Primary Outcomes
Terminal Elimination Rate Constant (Lambda[z])
Time Frame: Up to 140 days
Lambda\[z\] will be determined by selection of at least 3 data points on the terminal phase of the concentration-time curve.
Number of Participants with Vital Sign Abnormalities
Time Frame: Up to 2.5 years
Number of participants with vital sign (supine blood pressure \[BP\], heart rate, oral temperature, and respiratory rate) abnormalities will be reported.
Number of Participants with Electrocardiogram (ECG) Abnormalities
Time Frame: Up to 2.5 years
Number of participants with resting triplicate 12-lead ECG abnormalities will be reported.
Maximum Concentration (Cmax)
Time Frame: Up to 140 days
Cmax will be determined directly from the concentration-time profile.
Time to Cmax (Tmax)
Time Frame: Up to 140 days
Time to Cmax will be determined directly from the concentration-time profile.
Number of Participants with Concomitant Medication Use
Time Frame: Up to 2.5 years
Number of participants with concomitant medication use will be reported.
Number of Participants with Adverse events (AEs) and Serious AEs (SAEs)
Time Frame: Up to 2.5 years
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.
Number of Participants with Laboratory Abnormalities
Time Frame: Up to 2.5 years
Number of participants with laboratory (haematology, coagulation, clinical chemistry, serum inflammatory cytokine profile, and urinalysis) abnormalities will be reported.
Number of Participants with Physical Examinations Abnormalities
Time Frame: Up to 2.5 years
Number of participants with physical examinations abnormalities will be reported.
Area Under the Concentration-time Curve (AUC) From Predose (Time 0) to the end of the Dosing Period (AUC0-tau)
Time Frame: Up to 140 days
AUC0-tau will be calculated using the linear-log trapezoidal rule.
AUC From Predose (Time 0) to the Time of the Last Quantifiable Concentration (AUClast)
Time Frame: Up to 140 days
AUClast will be calculated using the linear-log trapezoidal rule.
AUC From Predose (Time 0) to 168 Hours Postdose (AUC0-168 )
Time Frame: Predose up to 168 hours postdose
AUC0-168 is AUC from predose (time 0) to 168 hours postdose.
Terminal Elimination Half-life
Time Frame: Up to 140 days
Terminal elimination half-life calculated as: ln2/Lambda\[z\]
Total body clearance (CL)
Time Frame: Up to 140 days
CL is defined as total body clearance.
Secondary Outcomes
- Number of Participants with Neutralizing Antibodies (NAbs)(Up to 2.5 years)
- Number of Participants with Anti-drug Antibodies (ADAs)(Up to 2.5 years)