Description:
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.
Title
- Brief Title: First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients
- 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
Clinical Trial IDs
- ORG STUDY ID:
SYD985.001
- NCT ID:
NCT02277717
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| SYD985 (trastuzumab vc-seco-DUBA) | | SYD985 (trastuzumab vc-seco-DUBA) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| SYD985 (trastuzumab vc-seco-DUBA) | Experimental | HER2-targeting Antibody-Drug Conjugate | - SYD985 (trastuzumab vc-seco-DUBA)
|
Eligibility Criteria
Main Inclusion Criteria:
1. 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;
2. For Part II: HER2 tumor status as defined in the protocol;
3. ECOG performance status ≤ 1;
4. Life expectancy > 12 weeks;
5. Adequate organ function;
6. For Part II: measurable disease.
Main Exclusion Criteria:
1. Anthracycline treatment within 3 months and/or abnormal cardiac biomarker values;
2. Other anticancer therapy (except for LHRH agonists) within 4 weeks (6 weeks for
nitrosoureas and mitomycin C);
3. History of infusion-related reactions and/or hypersensitivity to trastuzumab or (ado-)
trastuzumab emtansine;
4. Severe, uncontrolled systemic disease;
5. 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;
6. History of clinically significant CV disease;
7. Symptomatic brain metastasis, or therapy for brain metastasis (excluding PCI and
dexamethasone treatment with stable or decreasing daily dose) within 4 weeks.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of dose-limiting toxicities |
| Time Frame: | 21 days |
| Safety Issue: | |
| Description: | first cycle |
Secondary Outcome Measures
| Measure: | Number of patients with adverse events |
| Time Frame: | up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Safety Issue: | |
| Description: | |
| Measure: | Change from baseline in hematology and blood chemistry parameters |
| Time Frame: | Baseline and every cycle up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Number of patients with antibodies against SYD985 |
| Time Frame: | Baseline and every cycle up to 2 years |
| Safety Issue: | |
| Description: | |
| Measure: | Objective response rate |
| Time Frame: | Baseline and every two cycles up to 2 years |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Byondis B.V. |
Trial Keywords
- cancer
- metastasis
- HER2
- trastuzumab
- duocarmycin
- SYD985
- antibody-drug conjugate
- ADC
- trastuzumab vc-seco-DUBA
Last Updated
July 15, 2020
