* Phase 1 study with ADC BYON3521 in solid tumours expressing c-MET
Research type
Research Study
Full title
A first-in-human dose-escalation and expansion trial with the antibody-drug conjugate BYON3521 to evaluate the safety, pharmacokinetics and efficacy in patients with c-MET expressing locally advanced or metastatic solid tumours.
IRAS ID
305655
Contact name
Udai Banerji
Contact email
Sponsor organisation
Byondis BV
Eudract number
2021-003846-19
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 10 months, 4 days
Research summary
Research Summary
BYON3521 is a new antibody-drug conjugate that is being developed by Byondis BV for the treatment of cancer. BYON3521 consists of two parts. The antibody part binds to a protein found on different types of cancer cells (c-MET protein) thus allowing BYON3521 to enter the cell. The second part of BYON3521, a chemotherapy, is freed up inside the cancer cell to destroy it. BYON3521 has the potential to be an effective treatment for many cancers that have high levels of c-MET protein with fewer side effects than chemotherapy.
BYON3521 will be studied in humans for the first time in Study BYON3521.001. The Study consists of two parts: a dose escalation part and an expansion part. Around 30 patients over 18 years with c-MET-positive cancer will be enrolled in the dose escalation part. Several increasing doses of BYON3521 will be tested in small groups of cancer patients to determine the recommended dose for the expansion part. Up to 120 patients will participate in the expansion part in which the safety and effectiveness of BYON3521 will be studied.
Patients who agree to participate in the Study and pass screening will be receiving BYON3521 every 3 weeks until their cancer worsens or they have unacceptable side effects. BYON3521 will be given as an infusion into a vein over 30-60 mins.
After stopping treatment with BYON3521 patients will have a treatment discontinuation visit and a follow-up visit. Patients in the expansion part will also be followed up for survival status every 3 months.
The assessments for the Study include evaluation of medical history and use of other medications, documenting of any side effects, physical examinations, vital signs, eye exams, ECGs, blood and urine tests, pregnancy tests in females, tumour biopsy, CT or MRI scans.
The Study will run at around 20 sites worldwide with 4 sites in the UK.Summary of Results
CLINICAL TRIAL RESULTS SUMMARY A clinical trial to explore the safety and the effect of BYON3521 administered for the first time in humans with c-MET expressing locally advanced or metastatic solid tumors.
THANK YOU!
Thank you to those who participated in this clinical trial with BYON3521. Without trial patients, development of new medications would not be possible. Participation in this trial has helped researchers to understand how BYON3521 works and to see how safe it is. It has also provided researchers with important information about locally advanced or metastatic solid tumors (where the tumor has grown into nearby tissues or organs or spread to distant parts of the body) expressing c-MET.
The trial information given in this summary is from one trial only and must not be used to make medical decisions. This drug is not yet approved, and the outcomes of this trial may not apply to all patients. Do not change your current medical treatment without consulting your doctor.
OVERVIEW
Why was this trial done?
To see if BYON3521 is safe, to find out the highest amount of medicine that is tolerated, and to see how well it works in patients with c-MET expressing locally advanced or metastatic solid tumors.
Who took part in this trial?
The trial included 31 patients, comprising 20 men and 11 women, aged between 43 and 78 years, all diagnosed with c-MET expressing locally advanced or metastatic solid tumors, who were treated with BYON3521.
What treatment was tested in this trial?
All patients in the trial received BYON3521 in a fluid directly into a vein through infusion once every 3 weeks.
What were the main results of this trial?
Serious health issues were observed with the administration of BYON3521 at amounts of 4.8 mg/kg and 6.4 mg/kg. The health issues experienced included a decrease in a specific white blood cell count, skin reaction, and eye disorders.
What were the side effects?
In this trial, 29 patients (93.5%) experienced side effects related to BYON3521. The most experienced side effects (20% of patients or more) were tiredness (38.7%), decreased appetite (35.5%), nausea (feeling sick; 29.0%), and vomiting (25.8%).
WHAT ARE C-MET–EXPRESSING LOCALLY ADVANCED OR METASTATIC SOLID TUMORS?
Some cancers can be characterized by the overexpression of the c-MET protein in different types of cancer cells, leading to c-MET expressing locally advanced or metastatic solid tumors. These types of tumors may affect different parts of the body, such as the lungs, gastric system, kidney, ovaries and cervix, prostate, and salivary glands. People living with this cancer may experience symptoms that could include high blood pressure, constipation, cough and tiredness. BYON3521 is a medicine that is being tested for the treatment of c-MET expressing cancers.
WHAT WAS THE PURPOSE OF THIS CLINICAL TRIAL?
This trial was designed to answer these questions:
• Is BYON3521 safe when administered to patients with c-MET–expressing locally advanced or metastatic solid tumors?
• What is the highest amount of BYON3521 that is tolerated?
• How well does BYON3521 work in patients with c-MET–expressing locally ad-vanced or metastatic solid tumors?
HOW WAS THIS TRIAL DONE?
Who took part in this trial?
This trial included 31 patients, comprising 20 men and 11 women, aged between 43 and 78 years, all diagnosed with c-MET–expressing advanced or metastatic solid tumors.
Where did this trial take place?
This trial took place in 4 countries: 11 patients were treated in the Netherlands, 10 patients in Belgium, 5 patients in Italy, and 5 patients in Great Britain.
When did this trial take place?
This trial started in March 2022 and ended in April 2024.
The trial included 2 parts to be performed consecutively. However, BYON3521 did not work as well as it was expected in Part 1. Therefore, the trial was stopped early, and Part 2 was not performed.
What treatment was tested in this trial?
All patients in the trial received BYON3521 in different amounts, ranging from 0.8 mg/kg to 6.4 mg/kg, by infusion.
What has been completed?
Before treatment, the trial doctor checked the health of each patient to ensure they could participate in the trial. Individuals aged 18 years or older, diagnosed with c-MET–expressing locally advanced or metastatic solid tumors participated in the trial. The trial was planned to be performed in 2 parts:
• Part 1: BYON3521 was to be administered in different amounts, ranging from 0.8 mg/kg to 6.4 mg/kg, until reaching the highest tolerated amount.
• Part 2: The highest amount of BYON3521 that is tolerated from Part 1 was to be ad-ministered to different groups of patients, based on their type of cancer.
Patients had to sign an agreement to participate in the trial before any tests were performed. In Part 1, 31 patients were treated with different amounts of BYON3521 once every 3 weeks by infusion. The trial doctor checked for any health issues experienced by the patients and for any improvement or regression in cancer at each visit. Furthermore, during some of these visits, blood samples were collected at different timepoints to measure the amount of BYON3521 in the blood.
WHAT ARE THE MAIN RESULTS OF THIS TRIAL?
Overall, the researchers learned that:
Serious health issues were observed with the administration of BYON3521 at amounts of 4.8 mg/kg and 6.4 mg/kg. The health issues observed at these amounts included a decrease of a specific white blood cell count in 1 patient who received 4.8 mg/kg, skin reaction in 1 patient who received 6.4 mg/kg and 2 different eye disorders in 1 patient who received 6.4 mg/kg.
None of the patients in the trial had a partial or complete improvement in their cancer after administration of BYON3521.
WHAT WERE THE SIDE EFFECTS?
In this trial, some patients experienced side effects. Side effects are unwanted medical events that happen during the trial, which the trial doctor (investigator) believes could have been caused by the treatments in the trial.
Side effects were experienced by 29 out of 31 patients (93.5%). Of these, 6 patients had to stop BYON3521 administration because of the side effects. The most experienced side effects (in at least 20% of patients in the trial) were tiredness (12 out of 31 patients [38.7%]), decreased appetite (11 out of 31 patients [35.5%]), nausea (9 out of 31 patients [29.0%]), and vomiting (8 out of 31 patients [25.8%]). Additionally, 4 out of 31 patients (12.9%) had serious side effects: infection of the parts of the body that collect and pass out urine, decrease in the number of a type of white blood cell, inflammation in the lungs, and skin reaction (each in 1 out of 31 patients [3.2%]). There were no deaths during the trial, but 6 patients died up to 30 days after treatment with BYON3521 was stopped.
WHAT WAS LEARNED FROM THIS TRIAL?
Findings from this trial will be used in other studies to guide the safety of BYON3521 when administered to patients with c-MET–expressing cancer.
WHERE CAN I FIND MORE INFORMATION ABOUT THIS TRIAL?
Results from this trial may be presented in a different way in other documents.
Trial Title A First-in-human Dose-escalation and Expansion Trial with the Antibody-drug Conjugate BYON3521 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients with c-MET–expressing Locally Advanced or Metastatic Solid Tumors.Public Trial Title A clinical trial to explore the safety and the effect of BYON3521 for the first time in humans with c-MET expressing locally advanced or metastatic solid tumors
Protocol Number BYON3521.001
EudraCT Number 2021-003846-19 (EU CT number is not available since this trial was not transferred to EU CTR)
Study Sponsor Byondis BV / https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.byondis.com%252F%2FNBTI%2FWpW4AQ%2FAQ%2F86c13205-f742-43d3-8351-7c1e9364c7a3%2F2%2FfMAlFcbc1C&data=05%7C02%7Coxforda.rec%40hra.nhs.uk%7Ca5f02323694545db221708dce916ee14%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638641531892188094%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=ydnJK%2Bffy%2FGQM4ZPMUaXciIL9cX1NJ3egp9JnCJ9dA8%3D&reserved=0
Please email any questions to mailto: clinicaltrials@byondis.com
This trial is also registered on https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT05323045%2FNBTI%2FWpW4AQ%2FAQ%2F86c13205-f742-43d3-8351-7c1e9364c7a3%2F3%2FQACBgdMHtM&data=05%7C02%7Coxforda.rec%40hra.nhs.uk%7Ca5f02323694545db221708dce916ee14%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638641531892208104%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=c5KNmascLEa4kSxBMzutcgRFOmY2EA9%2BuB6Bi5KDZ8s%3D&reserved=0
ARE THERE PLANS FOR FURTHER TRIALS?
No further trials are planned.REC name
South Central - Oxford A Research Ethics Committee
REC reference
22/SC/0312
Date of REC Opinion
9 Nov 2021
REC opinion
Further Information Favourable Opinion