Ovarian Neoplasms
Conditions
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.
Interventions
BIOLOGICALTilvestamab
Tilvestamab will be administered as IV infusion.
Sponsors
BerGenBio ASA
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total body clearance (CL) | Up to 140 days | CL is defined as total body clearance. |
| Terminal Elimination Rate Constant (Lambda[z]) | 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. |
| Terminal Elimination Half-life | Up to 140 days | Terminal elimination half-life calculated as: ln2/Lambda\[z\] |
| Number of Participants with Adverse events (AEs) and Serious AEs (SAEs) | 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 | 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 Vital Sign Abnormalities | 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 | Up to 2.5 years | Number of participants with resting triplicate 12-lead ECG abnormalities will be reported. |
| Number of Participants with Physical Examinations Abnormalities | Up to 2.5 years | Number of participants with physical examinations abnormalities will be reported. |
| Number of Participants with Concomitant Medication Use | Up to 2.5 years | Number of participants with concomitant medication use will be reported. |
| Maximum Concentration (Cmax) | Up to 140 days | Cmax will be determined directly from the concentration-time profile. |
| Time to Cmax (Tmax) | Up to 140 days | Time to Cmax will be determined directly from the concentration-time profile. |
| Area Under the Concentration-time Curve (AUC) From Predose (Time 0) to the end of the Dosing Period (AUC0-tau) | 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) | 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 ) | Predose up to 168 hours postdose | AUC0-168 is AUC from predose (time 0) to 168 hours postdose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Neutralizing Antibodies (NAbs) | Up to 2.5 years | Number of participants with NAbs will be reported. |
| Number of Participants with Anti-drug Antibodies (ADAs) | Up to 2.5 years | Number of participants with ADAs will be reported. |
Countries
Norway, Singapore, South Korea, United Kingdom
Outcome results
None listed