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

NCT04893551 | Terminated Phase 1 DMC

• 2 other identifiers: BGB149-1022020-001382-36
• Study Type: interventional
• Target: 16
• Locations: 4 countries
• Sites: 9

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.

Conditions

Ovarian Neoplasms

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (2)

• Number of Participants with Anti-drug Antibodies (ADAs)

  Up to 2.5 years

• Number of Participants with Neutralizing Antibodies (NAbs)

  Up to 2.5 years

Study Arms (1)

Tilvestamab

EXPERIMENTAL

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

Interventions

Tilvestamab BIOLOGICAL

Tilvestamab will be administered as IV infusion.

Also known as: BGB149

Tilvestamab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BerGenBio ASA: lead

Study Sites (9)

Haukeland University Hospital Bergen

Bergen, Norway

Location

National University Hospital

Singapore, Singapore

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Yonsei University Health System- Severance Hospital

Seoul, South Korea

Location

Western General Hospital

Edinburgh, United Kingdom

Location

Guys and St Thomas' NHS Foundation Trust

London, United Kingdom

Location

Imperial College London, Hammersmith Hospital

London, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Related Publications (1)

• Sooi K, Tan TZ, Kim JW, Lee JY, Kim BG, Micklem D, Jackson A, Pinato DJ, Gourley C, Kristeleit R, Blagden SP, Bjorge L, Tan DSP. A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients. Br J Cancer. 2025 Oct;133(6):896-908. doi: 10.1038/s41416-025-03090-6. Epub 2025 Jul 22.

  PMID: 40696160 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Akil Jackson

  BerGenBio ASA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 19, 2021
• Study Start: February 25, 2021
• Primary Completion: June 27, 2022
• Study Completion: June 27, 2022
• Last Updated: April 20, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 5 years following article publication
• 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.

Locations

SG (1); GB (4); KR (3); NO (1)