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

• ClinicalTrials.gov Identifier: NCT02277717
• Recruitment Status: Completed
• First Posted: October 29, 2014
• Last Update Posted: August 14, 2023
• Sponsor: Byondis B.V.
• Information provided by (Responsible Party): Byondis B.V.

Study Description

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 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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 185 participants
• Allocation: N/A
• 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
• Actual Study Completion Date: October 2019

Arms and Interventions

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.

Outcome Measures

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 ]

Eligibility Criteria

• 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.

Contacts and Locations

Locations

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

Byondis B.V.

Investigators

• Study Director: Ellen Mommers, PhD; Synthon Biopharmaceuticals B.V., The Netherlands

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Menderes 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.

• Responsible Party: Byondis B.V.
• ClinicalTrials.gov Identifier: NCT02277717
• Other Study ID Numbers: SYD985.001
• First Posted: October 29, 2014
• Last Update Posted: August 14, 2023
• Last Verified: August 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Byondis B.V.:

cancer; metastasis; HER2; trastuzumab; duocarmycin; SYD985; antibody-drug conjugate; ADC; trastuzumab vc-seco-DUBA

Additional relevant MeSH terms:

Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents