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

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

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 Overview

• Status: Terminated
• Conditions: Ovarian Neoplasms
• Intervention / Treatment: Biological: Tilvestamab

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Yonsei University Health System- Severance Hospital
• Norway
  • Bergen, Norway
    • Haukeland University Hospital Bergen
• Singapore
  • Singapore, Singapore
    • National University Hospital
• United Kingdom
  • Edinburgh, United Kingdom
    • Western General Hospital
  • London, United Kingdom
    • Guys and St Thomas' NHS Foundation Trust
  • London, United Kingdom
    • Imperial College London, Hammersmith Hospital
  • Oxford, United Kingdom
    • Churchill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Biological: Tilvestamab; Tilvestamab will be administered as IV infusion.; Other Names: BGB149

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BerGenBio ASA
• Investigators: Study Director: Akil Jackson, BerGenBio ASA

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2021
• Primary Completion (Actual): June 27, 2022
• Study Completion (Actual): June 27, 2022

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 20, 2023
• Last Update Submitted That Met QC Criteria: April 18, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms
• Other Study ID Numbers: BGB149-102; 2020-001382-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in the article, after deidentification [text, tables, figures and appendices].
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication
• IPD Sharing Access Criteria: Proposal should be directed to HYPERLINK "mailto:clinical@bergenbio.com" clinical@bergenbio.com. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No