Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors

NCT04235101 | Completed Phase 1

• 1 other identifier: SYD985.004
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 6

Brief Summary

SYD985.004 is a two-part phase I study with the antibody-drug conjugate SYD985 in combination with niraparib aimed at evaluating safety, pharmacokinetics and efficacy in patients with HER2-expressing locally advanced or metastatic solid tumours.

Conditions

Solid Tumor

Keywords

Solid Tumor; Anti-body Drug Conjugate; ADC; niraparib

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 and niraparib

  Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months

• Peak plasma concentration of SYD985 and niraparib

  Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months

• 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 + Niraparib

EXPERIMENTAL

SYD985, Intravenous, every 3 weeks (Q3W) Niraparib taken orally and either 100 mg, 200 mg or 300 mg once daily for either 1, 2 or 3 weeks.

Drug: SYD985 + Niraparib

Interventions

SYD985 + Niraparib DRUG

SYD985 powder for concentrate for solution for infusion Niraparib 100 mg per hard capsule

Also known as: (vic-)trastuzumab duocarmazine + Zejula

SYD985 + Niraparib

Eligibility Criteria

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

You may qualify if:

• Male or female, age ≥ 18 years at the time of signing first informed consent;
• Patient with a histologically-confirmed, locally advanced or metastatic tumour 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: breast cancer, ovarian cancer or endometrial carcinoma/carcinosarcoma;
• HER2 tumor status at least 1+ as assessed by immunohistochemistry (IHC) as determined by the local laboratory;
• Presence of a tumor lesion accessible for biopsy and patient should be willing to undergo a fresh biopsy for central HER2 testing and genetic testing, unless adequate (biopsy) tumour material is available obtained \< 6 months prior to signing the main informed consent;
• At least one measurable cancer lesion as defined by the Response Evaluation Criteria for Solid Tumours (RECIST version 1.1);
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1;
• Adequate organ function.

You may not qualify if:

• Having been treated with:
• DUBA-containing ADCs at any time;
• Anthracycline treatment within 8 weeks prior to start of study treatment;
• Other anticancer therapy including chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to start of study treatment or 5 times the half-life of the therapy, whichever is shorter;
• Radiotherapy within 4 weeks prior to start of study treatment or within 1 week for palliative care (as long as the lungs were not exposed);
• Hormone therapy within 1 week prior to start of study treatment. The patient must have sufficiently recovered from any treatment-related toxicities to NCI CTCAE Grade ≤ 1 (except for toxicities not considered a safety risk for the patient at the investigator's discretion);
• History or presence of keratitis;
• Left ventricular ejection fraction (LVEF) \< 50% as assessed by either echocardiography or multigated acquisition (MUGA) scan at screening, or a history of clinically significant decrease in LVEF during previous trastuzumab containing treatment leading to permanent discontinuation of treatment;
• History (within 6 months prior to start of study treatment) or presence of clinically significant cardiovascular disease such as unstable angina, congestive heart failure, myocardial infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication;
• History or presence of idiopathic pulmonary fibrosis, organizing pneumonia (e.g. bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan;
• Severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) at screening;
• Symptomatic brain metastases, brain metastasis requiring steroids to manage symptoms or treatment for brain metastases within 8 weeks prior to start of study treatment.

Sponsors & Collaborators

• Byondis B.V.: lead

Study Sites (6)

University Hospital Antwerp, BE

Antwerp, 2650, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Radboud University Medical Center/ NL

Nijmegen, 6500 HB, Netherlands

Location

The Royal Marsden NHS Foundation Trust

London, SM2 5PT, United Kingdom

Location

The Christie NHS Foundation Trust/ UK

Manchester, M20 4BX, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust/UK

Newcastle, NE7 7DN, United Kingdom

Location

MeSH Terms

Interventions

trastuzumab duocarmazine; niraparib

Study Officials

• Norbert Koper

  Byondis 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: January 16, 2020
• First Posted: January 21, 2020
• Study Start: June 22, 2020
• Primary Completion: April 24, 2023
• Study Completion: April 24, 2023
• Last Updated: January 5, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); NL (1); BE (2)