Solid TumorsPhase 1NCT02277717
First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients
A Phase 1 study testing SYD985 (trastuzumab vc-seco-DUBA) in people with Solid Tumors, run by Byondis B.V. at 15 sites in 4 countries.
Trial summary
The purpose of this study is to evaluate the safety of a new medicinal drug SYD985 at different dose levels in patients with cancer, to understand how SYD985 is handled by the body and to evaluate the effect of SYD985 on the cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumors
- What is being tested?
- SYD985 (trastuzumab vc-seco-DUBA)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 185 participants
- Where
- 15 sitesin 4 countries
- Study dates
- Oct 2014to Oct 2019
- 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
Main Inclusion Criteria:
- Patient with histologically-confirmed, locally advanced or metastatic tumor who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:
- Part I: solid tumors of any origin;
- Part II: breast, gastric, urothelial and endometrial tumors;
- For Part II: HER2 tumor status as defined in the protocol;
- ECOG performance status ≤ 1;
- Life expectancy > 12 weeks;
- Adequate organ function;
- For Part II: measurable disease.
Main Exclusion Criteria:
- Anthracycline treatment within 3 months and/or abnormal cardiac biomarker values;
- Other anticancer therapy (except for LHRH agonists) within 4 weeks (6 weeks for nitrosoureas and mitomycin C);
- History of infusion-related reactions and/or hypersensitivity to trastuzumab or (ado-) trastuzumab emtansine;
- Severe, uncontrolled systemic disease;
- LVEF < 55%, or a history of absolute decrease in LVEF of ≥ 10% points to < 50% during previous treatment with trastuzumab or (ado-)trastuzumab emtansine, or a history of decrease in LVEF to < 40% during previous treatment with trastuzumab or (ado-)trastuzumab emtansine;
- History of clinically significant CV disease;
- Symptomatic brain metastasis, or therapy for brain metastasis (excluding PCI and dexamethasone treatment with stable or decreasing daily dose) within 4 weeks.
Trial locations and contacts
15 sites in 4 countries.
15 sites in 4 countries
Netherlands4 sites
NKI-AvL
Amsterdam
UMC
Groningen
Radboud UMC
Nijmegen
UMC
Rotterdam
Spain4 sites
Institut Catala d'Oncologia
Barcelona
Vall d'Hebron University Hospital
Barcelona
START Madrid-CIOCC
Madrid
START Madrid-FJD
Madrid
United Kingdom4 sites
Beatson Institute for Cancer Research
Glasgow
The Christie NHS Foundation Trust
Manchester
Churchill Hospital
Oxford
Royal Marsden / Institute of Cancer Research
Sutton
About this study
Official title: A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors
The purpose of this study is to evaluate the safety of a new medicinal drug SYD985 at different dose levels in patients with cancer, to understand how SYD985 is handled by the body and to evaluate the effect of SYD985 on the cancer.
Read the detailed description
Cancer cells can have different kinds of proteins on their cell surface; one of these is the protein HER2. HER2 plays an important role in the development of cancer. High expression of HER2 is related to poor prognosis. Although several cancer drugs are available that work via the HER2 protein, a substantial portion of these patients still does not benefit from these treatments.
The new cancer drug SYD985 is being developed by Synthon Biopharmaceuticals B.V. SYD985 is an antibody-drug conjugate and consists of two parts: an antibody and a linker-drug moiety containing a toxin. The antibody part binds to HER2 on the surface of the cancer cell. When SYD985 binds to this cancer cell, it will be internalized by the cell. After proteolytic cleavage of the linker, the toxin will be split off in the cell and the cancer cell will be killed. Thus, SYD985 can be considered as a form of targeted chemotherapy.
This is the first study in which SYD985 is administered to humans. The study consists of two parts:
Part I is the dose-escalation part in which a low dose of SYD985 is given to three cancer patients. If it is well tolerated, a higher dose of SYD985 will be given to 3 other cancer patients. This will continue until a further dose increase is not safe anymore.
In Part II of the study, several groups of patients with a specific type of cancer will receive the SYD985 dose which has been selected for further evaluation.
All patients from both parts of the study will receive SYD985 infusions every three weeks until progression of the cancer or unacceptable toxicity develops.
- Conditions
- Solid Tumors
- Being tested
- SYD985 (trastuzumab vc-seco-DUBA)
- Keywords
- cancer, metastasis, HER2, trastuzumab, duocarmycin, SYD985, antibody-drug conjugate, ADC, trastuzumab vc-seco-DUBA
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYD985 (trastuzumab vc-seco-DUBA)Drug
IV (in the vein) infusion every three weeks. Number of Cycles: until cancer progression or unacceptable toxicity develops. Different doses.
| Study group | Role | What they receive |
|---|---|---|
| SYD985 (trastuzumab vc-seco-DUBA) | Experimental | HER2-targeting Antibody-Drug Conjugate Receives: Drug: SYD985 (trastuzumab vc-seco-DUBA) |
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
Measured: Baseline, Days 1,2,3,4,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 2 years
Peak plasma concentration of SYD985
Measured: Baseline, Days 1,2,3,4,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 2 years
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 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 posted29 Oct 2014 (estimated)
- Study startOct 2014
- Primary completionJan 2019
- Study completionOct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Solid TumorsStudies 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
- 185 participants (actual)
Sponsor and investigators
- Lead sponsor
- Byondis B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ellen Mommers, PhD, Study director, Synthon Biopharmaceuticals B.V., The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02277717
- Sponsor's protocol ID
- SYD985.001
- Status last verified
- Aug 2023
- First submitted
- 21 Oct 2014
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Banerji U, van Herpen CML, Saura C, Thistlethwaite F, Lord S, Moreno V, Macpherson IR, Boni V, Rolfo C, de Vries EGE, Rottey S, Geenen J, Eskens F, Gil-Martin M, Mommers EC, Koper NP, Aftimos P. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Aug;20(8):1124-1135. doi: 10.1016/S1470-2045(19)30328-6. Epub 2019 Jun 27.
PubMed 31257177Menderes G, Bonazzoli E, Bellone S, Black J, Altwerger G, Masserdotti A, Pettinella F, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression. Gynecol Oncol. 2017 Jul;146(1):179-186. doi: 10.1016/j.ygyno.2017.04.023. Epub 2017 May 1.
PubMed 28473206
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Part First-in-human Phase I Study (With Expanded Cohorts) With the Antibody-drug Conjugate SYD985 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With Locally Advanced or Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT02277717
- Acronym / sponsor ID
- SYD985.001
- Conditions
- Solid Tumors
- Keywords
- cancer, metastasis, HER2, trastuzumab, duocarmycin, SYD985, antibody-drug conjugate, ADC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 185 participants (actual)
- Lead sponsor
- Byondis B.V.Industry (pharma, biotech, devices)
- Study start
- Oct 2014 (actual)
- Primary completion
- Jan 2019 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 29 Oct 2014 (estimated)
- 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.
The purpose of this study is to evaluate the safety of a new medicinal drug SYD985 at different dose levels in patients with cancer, to understand how SYD985 is handled by the body and to evaluate the effect of SYD985 on the cancer.
Detailed description
Cancer cells can have different kinds of proteins on their cell surface; one of these is the protein HER2. HER2 plays an important role in the development of cancer. High expression of HER2 is related to poor prognosis. Although several cancer drugs are available that work via the HER2 protein, a substantial portion of these patients still does not benefit from these treatments.
The new cancer drug SYD985 is being developed by Synthon Biopharmaceuticals B.V. SYD985 is an antibody-drug conjugate and consists of two parts: an antibody and a linker-drug moiety containing a toxin. The antibody part binds to HER2 on the surface of the cancer cell. When SYD985 binds to this cancer cell, it will be internalized by the cell. After proteolytic cleavage of the linker, the toxin will be split off in the cell and the cancer cell will be killed. Thus, SYD985 can be considered as a form of targeted chemotherapy.
This is the first study in which SYD985 is administered to humans. The study consists of two parts:
Part I is the dose-escalation part in which a low dose of SYD985 is given to three cancer patients. If it is well tolerated, a higher dose of SYD985 will be given to 3 other cancer patients. This will continue until a further dose increase is not safe anymore.
In Part II of the study, several groups of patients with a specific type of cancer will receive the SYD985 dose which has been selected for further evaluation.
All patients from both parts of the study will receive SYD985 infusions every three weeks 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 (trastuzumab vc-seco-DUBA) | Experimental | Drug: SYD985 (trastuzumab vc-seco-DUBA)HER2-targeting Antibody-Drug Conjugate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 (trastuzumab vc-seco-DUBA)IV (in the vein) infusion every three weeks. Number of Cycles: until cancer progression or unacceptable toxicity develops. Different doses. | Drug | SYD985 (trastuzumab vc-seco-DUBA) |
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
Time frame: Baseline, Days 1,2,3,4,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 2 years
Peak plasma concentration of SYD985
Time frame: Baseline, Days 1,2,3,4,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 2 years
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 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 14 Aug 2023.
- Derived from this study: PubMed 31257177Banerji U, van Herpen CML, Saura C, Thistlethwaite F, Lord S, Moreno V, Macpherson IR, Boni V, Rolfo C, de Vries EGE, Rottey S, Geenen J, Eskens F, Gil-Martin M, Mommers EC, Koper NP, Aftimos P. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019 Aug;20(8):1124-1135. doi: 10.1016/S1470-2045(19)30328-6. Epub 2019 Jun 27.
- Derived from this study: PubMed 28473206Menderes G, Bonazzoli E, Bellone S, Black J, Altwerger G, Masserdotti A, Pettinella F, Zammataro L, Buza N, Hui P, Wong S, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression. Gynecol Oncol. 2017 Jul;146(1):179-186. doi: 10.1016/j.ygyno.2017.04.023. Epub 2017 May 1.
- Individual participant dataSharing planned: Undecided
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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.
Ellen Mommers, PhD study director
Synthon Biopharmaceuticals B.V., The Netherlands
15 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SYD985 (trastuzumab vc-seco-DUBA) in people with Solid Tumors, run by Byondis B.V. at 15 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 14 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Netherlands, Spain, United Kingdom, Belgium. 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?
On the ClinicalTrials.gov record for NCT02277717, which also lists 2 linked publications.
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 14 Aug 2023.