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First-in-human Study With the Antibody-drug Conjugate SYD985 to Evaluate Safety and Efficacy in Cancer Patients

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ClinicalTrials.gov Identifier: NCT02277717
Recruitment Status : Active, not recruiting
First Posted : October 29, 2014
Last Update Posted : February 12, 2019
Sponsor:
Information provided by (Responsible Party):
Synthon Biopharmaceuticals BV

Brief 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.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: SYD985 (trastuzumab vc-seco-DUBA) Phase 1

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 BV. 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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 185 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 2014
Actual Primary Completion Date : January 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SYD985 (trastuzumab vc-seco-DUBA)
HER2-targeting Antibody-Drug Conjugate
Drug: 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.




Primary Outcome Measures :
  1. Incidence of dose-limiting toxicities [ Time Frame: 21 days ]
    first cycle


Secondary Outcome Measures :
  1. Number of patients with adverse events [ Time Frame: up to 2 years ]
  2. 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 ]
  3. 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 ]
  4. Change from baseline in hematology and blood chemistry parameters [ Time Frame: Baseline and every cycle up to 2 years ]
  5. Number of patients with antibodies against SYD985 [ Time Frame: Baseline and every cycle up to 2 years ]
  6. Objective response rate [ Time Frame: Baseline and every two cycles up to 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02277717


Locations
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Belgium
UZ
Antwerp, Belgium
Institut Jules Bordet
Brussels, Belgium
UZ
Gent, Belgium
Netherlands
NKI-AvL
Amsterdam, Netherlands
UMC
Groningen, Netherlands
Radboud UMC
Nijmegen, Netherlands
UMC
Rotterdam, Netherlands
Spain
Institut Catala d'Oncologia
Barcelona, Spain
Vall d'Hebron University Hospital
Barcelona, Spain
START Madrid-CIOCC
Madrid, Spain
START Madrid-FJD
Madrid, Spain
United Kingdom
Beatson Institute for Cancer Research
Glasgow, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
Churchill Hospital
Oxford, United Kingdom
Royal Marsden / Institute of Cancer Research
Sutton, United Kingdom
Sponsors and Collaborators
Synthon Biopharmaceuticals BV
Investigators
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Study Director: Ellen Mommers, PhD Synthon Biopharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Synthon Biopharmaceuticals BV
ClinicalTrials.gov Identifier: NCT02277717     History of Changes
Other Study ID Numbers: SYD985.001
First Posted: October 29, 2014    Key Record Dates
Last Update Posted: February 12, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Synthon Biopharmaceuticals BV:
cancer
metastasis
HER2
trastuzumab
duocarmycin
SYD985
antibody-drug conjugate
ADC
trastuzumab vc-seco-DUBA

Additional relevant MeSH terms:
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Antibodies
Immunoglobulins
Immunoconjugates
Trastuzumab
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents