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

NCT02277717 | Completed Phase 1 DMC

• 1 other identifier: SYD985.001
• Study Type: interventional
• Target: 185
• Locations: 4 countries
• Sites: 15

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.

Conditions

Solid Tumors

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities

  first cycle

  21 days

Secondary Outcomes (6)

• 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

Study Arms (1)

SYD985 (trastuzumab vc-seco-DUBA)

EXPERIMENTAL

HER2-targeting Antibody-Drug Conjugate

Drug: SYD985 (trastuzumab vc-seco-DUBA)

Interventions

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.

SYD985 (trastuzumab vc-seco-DUBA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Byondis B.V.: lead

Study Sites (15)

UZ

Antwerp, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

UZ

Ghent, Belgium

Location

NKI-AvL

Amsterdam, Netherlands

Location

UMC

Groningen, Netherlands

Location

Radboud UMC

Nijmegen, Netherlands

Location

UMC

Rotterdam, Netherlands

Location

Institut Catala d'Oncologia

Barcelona, Spain

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

START Madrid-CIOCC

Madrid, Spain

Location

START Madrid-FJD

Madrid, Spain

Location

Beatson Institute for Cancer Research

Glasgow, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Churchill Hospital

Oxford, United Kingdom

Location

Royal Marsden / Institute of Cancer Research

Sutton, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 31257177 DERIVED

• 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.

  PMID: 28473206 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

trastuzumab duocarmazine

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ellen Mommers, PhD

  Synthon Biopharmaceuticals B.V., The Netherlands

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 29, 2014
• Study Start: October 1, 2014
• Primary Completion: January 1, 2019
• Study Completion: October 1, 2019
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

NL (4); BE (3); GB (4); ES (4)