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.

Tracking Information

• First Submitted Date: October 21, 2014
• First Posted Date: October 29, 2014
• Last Update Posted Date: August 14, 2023
• Actual Study Start Date: October 2014
• Actual Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2014)

Incidence of dose-limiting toxicities [ Time Frame: 21 days ]

first cycle

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 27, 2014)

• Number of patients with adverse events [ Time Frame: up to 2 years ]
• 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 ]
• 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 ]
• Change from baseline in hematology and blood chemistry parameters [ Time Frame: Baseline and every cycle up to 2 years ]
• Number of patients with antibodies against SYD985 [ Time Frame: Baseline and every cycle up to 2 years ]
• Objective response rate [ Time Frame: Baseline and every two cycles up to 2 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

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
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

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.

Study Arms

Experimental: SYD985 (trastuzumab vc-seco-DUBA)

HER2-targeting Antibody-Drug Conjugate

Intervention: Drug: SYD985 (trastuzumab vc-seco-DUBA)

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 18, 2018): 185
• Original Estimated Enrollment (submitted: October 27, 2014): 76
• Actual Study Completion Date: October 2019
• Actual Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Netherlands, Spain, United Kingdom

Administrative Information

• NCT Number: NCT02277717
• Other Study ID Numbers: SYD985.001
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Byondis B.V.
• Original Responsible Party: Synthon BV
• Current Study Sponsor: Byondis B.V.
• Original Study Sponsor: Synthon BV
• Collaborators: Not Provided

Investigators

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

• PRS Account: Byondis B.V.
• Verification Date: August 2023