A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875

• Sponsor: Byondis B.V. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04202705
• Collaborator: (none)
• Enrollment: 31
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 34.1
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This is the first-in-human study with SYD1875, an antibody-drug conjugate (ADC) comprising of a humanized IgG1 monoclonal antibody directed against the 5T4 oncofetal antigen covalently conjugated to a duocarmycin-based linker-drug. This study includes a dose-escalation part (Part 1) in which the maximum tolerated dose (MTD) and recommended dose for expansion (RDE) will be determined, and an expansion part (Part 2) to evaluate efficacy and safety in specific patient cohorts.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor	Drug: SYD1875	Phase 1

Detailed Description

Cancer cells can have different kinds of proteins on their cell surface; one of these is the oncofetal antigen 5T4. 5T4 plays an important role in the development of cancer. Currently no drugs are available that work via the 5T4 antigen.

The new cancer drug SYD1875 is being developed by Byondis B.V. SYD1875 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 5T4 on the surface of the cancer cell. When SYD1875 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, SYD1875 can be considered as a form of targeted chemotherapy.

This is the first study in which SYD1875 is administered to humans. The study consists of two parts:

Part 1 is the dose-escalation part in which a low dose of SYD1875 is given to cancer patients. If it is well tolerated, a higher dose of SYD1875 will be given to other cancer patients until the maximum tolerated dose is reached.

In Part 2 of the study, groups of patients with a specific type of cancer will receive the SYD1875 dose which has been selected for further evaluation.

All patients from both parts of the study will receive SYD1875 infusions every three weeks until progression of the cancer or unacceptable toxicity develops.

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate SYD1875 to Evaluate the Safety, Pharmacokinetics and Efficacy in Patients With 5T4-expressing Locally Advanced or Metastatic Solid Tumours
• Actual Study Start Date: Feb 28, 2020
• Actual Primary Completion Date: Jun 22, 2022
• Anticipated Study Completion Date: Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SYD1875 5T4-targeting Antibody-Drug Conjugate	Drug: SYD1875; SYD1875 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 [21 days]

   Part 1

Secondary Outcome Measures

1. Objective response rate [21 days]

   Part 2

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

• Patient with histologically-confirmed, locally advanced or metastatic cancer who has progressed on standard therapy or for whom no standard therapy exists, with the following restriction:

• Part 1: solid tumours of any origin

• Part 2: three patient cohorts

• Tumour 5T4 membrane staining according protocol

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;

• Adequate organ function

• For Part 2: measurable disease

Main Exclusion Criteria:

• Having been treated with:

1. 5T4-targeting therapy at any time

2. Trastuzumab duocarmazine (SYD985) at any time

3. Other anticancer therapy within 4 weeks or as defined in the protocol

4. Hormone therapy within 1 week

• History or presence of keratitis, clinically significant renal disease, lung disease, or cardiovascular disease as specified in the protocol

• Symptomatic brain metastases, brain metastases requiring steroids or treatment for brain metastases within 8 weeks

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institut Jules Bordet	Brussels		Belgium
2	Institut Bergonié	Bordeaux		France
3	Centre Oscar Lambret	Lille		France

Sponsors and Collaborators

• Byondis B.V.

Investigators

• Study Director: Ellen Mommers, PhD, Byondis B.V., The Netherlands

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Byondis B.V.
• ClinicalTrials.gov Identifier: NCT04202705
• Other Study ID Numbers: SYD1875.001
• First Posted: Dec 17, 2019
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Byondis B.V.: ADC; 5T4; solid tumors; duocarmycin

Study Results

No Results Posted as of Aug 3, 2022