Solid TumorPhase 1NCT04235101
Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors
A Phase 1 study testing SYD985 + Niraparib in people with Solid Tumor, run by Byondis B.V. at 6 sites in 3 countries.
Trial summary
SYD985.004 is a two-part phase I study with the antibody-drug conjugate SYD985 in combination with niraparib aimed at evaluating safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumours. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- SYD985 + Niraparib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 22 Jun 2020to 24 Apr 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age ≥ 18 years at the time of signing first informed consent;
- Patient with a histologically-confirmed, locally advanced or metastatic tumour who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:
- Part 1: solid tumours of any origin;
- Part 2: breast cancer, ovarian cancer or endometrial carcinoma/carcinosarcoma;
- HER2 tumor status at least 1+ as assessed by immunohistochemistry (IHC) as determined by the local laboratory;
- Presence of a tumor lesion accessible for biopsy and patient should be willing to undergo a fresh biopsy for central HER2 testing and genetic testing, unless adequate (biopsy) tumour material is available obtained < 6 months prior to signing the main informed consent;
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- At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1);
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
- Adequate organ function.
Who cannot join
- Having been treated with:
- DUBA-containing ADCs at any time;
- Anthracycline treatment within 8 weeks prior to start of study treatment;
- Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to start of study treatment or 5 times the half-life of the therapy, whichever is shorter;
- Radiotherapy within 4 weeks prior to start of study treatment or within 1 week for palliative care (as long as the lungs were not exposed);
- Hormone therapy within 1 week prior to start of study treatment. The patient must have sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade ≤ 1 (except for toxicities not considered a safety risk for the patient at the investigator's discretion);
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- History or presence of keratitis;
- Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment;
- History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;
- History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;
- Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;
- Symptomatic brain metastases, brain metastasis requiring steroids to manage symptoms or treatment for brain metastases within 8 weeks prior to start of study treatment.
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United Kingdom3 sites
The Royal Marsden NHS Foundation Trust
London, SM2 5PT
The Christie NHS Foundation Trust/ UK
Manchester, M20 4BX
The Newcastle upon Tyne Hospitals NHS Foundation Trust/UK
Newcastle, NE7 7DN
Belgium2 sites
University Hospital Antwerp, BE
Antwerp, 2650
Institut Jules Bordet
Brussels, 1000
About this study
Official title: A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.
SYD985.004 is a two-part phase I study with the antibody-drug conjugate SYD985 in combination with niraparib aimed at evaluating safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumours.
Read the detailed description
This is an open-label, single-arm study in which patients with HER2-expressing locally advanced or metastatic solid tumours will be treated with both an anti-body drug conjugate SYD985 and a Poly (ADP-ribose) Polymerase (PARP) inhibitor niraparib. SYD985 is an antibody-drug conjugate and consists of two parts. The antibody part binds to a protein that exists on different types of cancer cells (HER2 protein). When SYD985 binds to this protein, it will be taken up by the cancer cell. The second part of the drug, a toxin, will be cleaved in the cell and subsequently kills the cancer cell. Niraparib blocks the action of enzymes PARP-1 and PARP-2, which help to repair damaged DNA in cells when the cells divide to make new cells. By blocking PARP enzymes, the damaged DNA in cancer cells cannot be repaired, and, as a result, the cancer cells die.
Part 1 includes patients with locally advanced or metastatic HER2-expressing solid tumours of any origin that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops. In this first part of the study, different doses of niraparib will be given for either 1, 2 or 3 weeks.
Part 2 includes patients with advanced or metastatic breast, ovarian or endometrial cancer that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops.
- Conditions
- Solid Tumor
- Being tested
- SYD985 + Niraparib
- Keywords
- Solid Tumor, Anti-body Drug Conjugate, ADC, niraparib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYD985 + NiraparibDrug
Also called (vic-)trastuzumab duocarmazine + Zejula
SYD985 powder for concentrate for solution for infusion Niraparib 100 mg per hard capsule
| Study group | Role | What they receive |
|---|---|---|
| SYD985 + Niraparib | Experimental | SYD985, Intravenous, every 3 weeks (Q3W) Niraparib taken orally and either 100 mg, 200 mg or 300 mg once daily for either 1, 2 or 3 weeks. Receives: Drug: SYD985 + Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicities
First cycle
Measured: 21 days
Secondary outcomes (6)
Number of patients with adverse events
Measured: up to 2 years
Area under the plasma concentration versus time curve (AUC) of SYD985 and niraparib
Measured: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months
Peak plasma concentration of SYD985 and niraparib
Measured: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months
Change from baseline in hematology and blood chemistry parameters
Measured: Baseline and every cycle up to 2 years
Number of patients with antibodies against SYD985
Measured: Baseline and every cycle up to 2 years
Objective response rate
Measured: Baseline and every two cycles for up to 6 months, subsequent every 4 cycles up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2020
- Study start22 Jun 2020
- Primary completion24 Apr 2023
- Study completion24 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Byondis B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Norbert Koper, Study director, Byondis B.V., The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04235101
- Sponsor's protocol ID
- SYD985.004
- Status last verified
- Jan 2024
- First submitted
- 16 Jan 2020
- Last updated
- 5 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.
- ClinicalTrials.gov ID
- NCT04235101
- Acronym / sponsor ID
- SYD985.004
- Conditions
- Solid Tumor
- Keywords
- Solid Tumor, Anti-body Drug Conjugate, ADC, niraparib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Byondis B.V.Industry (pharma, biotech, devices)
- Study start
- 22 Jun 2020 (actual)
- Primary completion
- 24 Apr 2023 (actual)
- Study completion
- 24 Apr 2023 (actual)
- First posted
- 21 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SYD985.004 is a two-part phase I study with the antibody-drug conjugate SYD985 in combination with niraparib aimed at evaluating safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumours.
Detailed description
This is an open-label, single-arm study in which patients with HER2-expressing locally advanced or metastatic solid tumours will be treated with both an anti-body drug conjugate SYD985 and a Poly (ADP-ribose) Polymerase (PARP) inhibitor niraparib. SYD985 is an antibody-drug conjugate and consists of two parts. The antibody part binds to a protein that exists on different types of cancer cells (HER2 protein). When SYD985 binds to this protein, it will be taken up by the cancer cell. The second part of the drug, a toxin, will be cleaved in the cell and subsequently kills the cancer cell. Niraparib blocks the action of enzymes PARP-1 and PARP-2, which help to repair damaged DNA in cells when the cells divide to make new cells. By blocking PARP enzymes, the damaged DNA in cancer cells cannot be repaired, and, as a result, the cancer cells die.
Part 1 includes patients with locally advanced or metastatic HER2-expressing solid tumours of any origin that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops. In this first part of the study, different doses of niraparib will be given for either 1, 2 or 3 weeks.
Part 2 includes patients with advanced or metastatic breast, ovarian or endometrial cancer that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SYD985 + Niraparib | Experimental | Drug: SYD985 + NiraparibSYD985, Intravenous, every 3 weeks (Q3W) Niraparib taken orally and either 100 mg, 200 mg or 300 mg once daily for either 1, 2 or 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female, age ≥ 18 years at the time of signing first informed consent;
- Patient with a histologically-confirmed, locally advanced or metastatic tumour who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:
- HER2 tumor status at least 1+ as assessed by immunohistochemistry (IHC) as determined by the local laboratory;
- Presence of a tumor lesion accessible for biopsy and patient should be willing to undergo a fresh biopsy for central HER2 testing and genetic testing, unless adequate (biopsy) tumour material is available obtained < 6 months prior to signing the main informed consent;
- At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1);
Key exclusion criteria (12 listed)
- Having been treated with:
- History or presence of keratitis;
- Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment;
- History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;
- History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SYD985 + NiraparibAlso: (vic-)trastuzumab duocarmazine + ZejulaSYD985 powder for concentrate for solution for infusion Niraparib 100 mg per hard capsule | Drug | SYD985 + Niraparib |
Primary outcome
Incidence of dose-limiting toxicities
Time frame: 21 days
First cycle
6 secondary outcomes
Number of patients with adverse events
Time frame: up to 2 years
Area under the plasma concentration versus time curve (AUC) of SYD985 and niraparib
Time frame: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months
Peak plasma concentration of SYD985 and niraparib
Time frame: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months
Change from baseline in hematology and blood chemistry parameters
Time frame: Baseline and every cycle up to 2 years
Number of patients with antibodies against SYD985
Time frame: Baseline and every cycle up to 2 years
Objective response rate
Time frame: Baseline and every two cycles for up to 6 months, subsequent every 4 cycles up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norbert Koper study director
Byondis B.V., The Netherlands
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SYD985 + Niraparib in people with Solid Tumor, run by Byondis B.V. at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom, Belgium, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicities (time frame: 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.