Study of BGB149 in Relapsed Platinum-resistant HGSOC Patients
Research type
Research Study
Full title
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
IRAS ID
286152
Contact name
Jonathan Krell
Contact email
Sponsor organisation
BerGenBio ASA
Eudract number
2020-001382-36
ISRCTN Number
ISRCTN00000000
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 7 months, 16 days
Research summary
Research Summary
The purpose of this study is to learn more about Tilvestamab. Tilvestamab is a potent and selective monoclonal antibody (manufactured equivalent to an immune protein normally made in the body) that targets and blocks activity of the AXL receptor, a protein that is abnormally over expressed in many disease conditions including cancer and fibrosis.
This study explores how well patients tolerate repeated dosing with Tilvestamab over time and at different dose levels and will evaluate Tilvestamab’s distribution in the body. The study will also examine how the drug interacts with and impacts the AXL protein target. Patients having conditions with increased AXL, that can be easily measured, represent the ideal patient population for this study. Over 70% of patients with the most common form of ovarian cancer (High Grade Serous type) that is resistant to chemotherapy have increased expression of AXL protein in their tumour, which drives chemotherapy resistance, tumour spread, and suppressed anticancer immunity. Such patients have few effective treatment options and are ideal to study the AXL blocking monoclonal antibody Tilvestamab.
This is an open label study testing different doses of Tilvestamab, which means that both patients and the study team will know who is receiving different doses of the study drug.
Study procedures include: physical examination, details of medical history and previous therapy, vital signs, serial biopsy samples (to study the impact of Tilvestamab on AXL function in the tumour through the course of the treatment), heart function tests, blood and urine tests (including measurement of the level of Tilvestamab circulating in the blood), ECG (recording of the heart), tumour assessment/ imaging tests, quality of life questionnaires and administration of the study drug.
This study will be run in approximately 10 hospitals in 5 countries and about 24 women with ovarian cancer are planned to participate.
Summary of Results
This study evaluated multiple ascending doses of tilvestamab (study drug) given via intravenous (IV) infusion every 2 weeks to women with Ovarian Cancer that has reoccurred after platinum (carboplatin or cisplatin) chemotherapy, a type of treatment that uses platinum to destroy ovarian cancer cells.
Tilvestamab blocks a protein called AXL, which is present in ovarian cancers; by blocking it the goal was to reduce the cancer’s ability to grow and spread.
This was the first study of tilvestamab in patients and so the main purpose of this study was to learn how safe the study drug is, how well patients tolerate the study drug, and to understand how the study drug is distributed in the blood and removed from the patient’s body. The study drug was given as a slow injection “a drip” into a vein every two weeks, and the plan was to treat patients with study drug on its own for up to 20 weeks or until checks on the patient showed that the cancer was growing.Overall, it was planned to enroll up to 24 patients in this study, with 16 patients receiving at least one dose of the study drug,15 of whom stopped treatment before the full 20 weeks.
SUMMARY OF RESULTS
On average, patients received study drug for about ten weeks. Almost all patients (14 of 16) experienced effects after starting treatment (176 in all) and in ten of the patients it was felt these might be related to the study drug, with three patients stopping the study drug due to these events. There were 26 side effects classified as serious, however none were suspected to be due to an unknown effect of the study drug. In one patient, the ovarian cancer was confirmed to progress on study resulting in death due to the disease. None of the patients experienced a reduction in the size of tumour on study, but 5 were classified to have stable disease during their time on study.
There were no concerns raised in the standardised monitoring of blood tests sent to the laboratory, vital signs, tracings of the electrical activity of the heart, physical examination by doctors and nurses, and other observations related to safety.
Conclusions: Tilvestamab was generally well tolerated, when given every 2 weeks at the doses studied, up to a maximum dose of 5 mg/kg, for up to 10 consecutive doses over 20 weeks.
The study was stopped by the company who makes the study drug, (early termination) without going into a second phase of study to take enrolment up to 24. This was not due to a concern over the study drug safety or tolerability. The company and study doctors agreed that further evaluation of the study drug would best be conducted using a study design which differed from this protocol, for the next phase of its development.REC name
London - Harrow Research Ethics Committee
REC reference
20/LO/1106
Date of REC Opinion
2 Dec 2020
REC opinion
Further Information Favourable Opinion