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

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: SYD985 (trastuzumab vc-seco-DUBA)

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 Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium
    • UZ
  • Brussels, Belgium
    • Institut Jules Bordet
  • Gent, Belgium
    • UZ
• Netherlands
  • Amsterdam, Netherlands
    • NKI-AVL
  • Groningen, Netherlands
    • UMC
  • Nijmegen, Netherlands
    • Radboud UMC
  • Rotterdam, Netherlands
    • UMC
• Spain
  • Barcelona, Spain
    • Vall d'Hebrón University Hospital
  • Barcelona, Spain
    • Institut Catala D'oncologia
  • Madrid, Spain
    • START Madrid-CIOCC
  • Madrid, Spain
    • START Madrid-FJD
• United Kingdom
  • Glasgow, United Kingdom
    • Beatson Institute for Cancer Research
  • Manchester, United Kingdom
    • The Christie NHS Foundation Trust
  • Oxford, United Kingdom
    • Churchill Hospital
  • Sutton, United Kingdom
    • Royal Marsden / Institute of Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities	first cycle	21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with adverse events	up to 2 years
Area under the plasma concentration versus time curve (AUC) of SYD985	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	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	Baseline and every cycle up to 2 years
Number of patients with antibodies against SYD985	Baseline and every cycle up to 2 years
Objective response rate	Baseline and every two cycles up to 2 years

Collaborators and Investigators

• Sponsor: Byondis B.V.
• Investigators: Study Director: Ellen Mommers, PhD, Synthon Biopharmaceuticals B.V., The Netherlands

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Actual): January 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: October 21, 2014
• First Submitted That Met QC Criteria: October 27, 2014
• First Posted (Estimated): October 29, 2014

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 10, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: cancer; HER2; trastuzumab; metastasis; ADC; antibody-drug conjugate; SYD985; duocarmycin; trastuzumab vc-seco-DUBA
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: SYD985.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED