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

• ClinicalTrials.gov Identifier: NCT04235101
• Recruitment Status: Active, not recruiting
• First Posted: January 21, 2020
• Last Update Posted: May 16, 2023
• Sponsor: Byondis B.V.
• Information provided by (Responsible Party): Byondis B.V.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: SYD985 + Niraparib	Phase 1

Detailed Description:

This is an open-label, single-arm study in which patients with HER2-expressing locally advanced or metastatic solid tumours will be treated with both an anti-body drug conjugate SYD985 and a Poly (ADP-ribose) Polymerase (PARP) inhibitor niraparib. SYD985 is an antibody-drug conjugate and consists of two parts. The antibody part binds to a protein that exists on different types of cancer cells (HER2 protein). When SYD985 binds to this protein, it will be taken up by the cancer cell. The second part of the drug, a toxin, will be cleaved in the cell and subsequently kills the cancer cell. Niraparib blocks the action of enzymes PARP-1 and PARP-2, which help to repair damaged DNA in cells when the cells divide to make new cells. By blocking PARP enzymes, the damaged DNA in cancer cells cannot be repaired, and, as a result, the cancer cells die.

Part 1 includes patients with locally advanced or metastatic HER2-expressing solid tumours of any origin that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops. In this first part of the study, different doses of niraparib will be given for either 1, 2 or 3 weeks.

Part 2 includes patients with advanced or metastatic breast, ovarian or endometrial cancer that showed progression on standard therapy or for whom no standard therapy exists. Patients will receive SYD985 infusions every three weeks in combination with niraparib until progression of the cancer or unacceptable toxicity develops.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Two-part Phase I Study With the Antibody-drug Conjugate SYD985 in Combination With Niraparib to Evaluate Safety, Pharmacokinetics and Efficacy in Patients With HER2-expressing Locally Advanced or Metastatic Solid Tumors.
• Actual Study Start Date: June 22, 2020
• Actual Primary Completion Date: April 24, 2023
• Estimated Study Completion Date: June 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: SYD985 + Niraparib; 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; SYD985 powder for concentrate for solution for infusion Niraparib 100 mg per hard capsule; Other Name: (vic-)trastuzumab duocarmazine + Zejula

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose-limiting toxicities [ Time Frame: 21 days ]
   First cycle

Secondary Outcome Measures :

1. Number of patients with adverse events [ Time Frame: up to 2 years ]
2. Area under the plasma concentration versus time curve (AUC) of SYD985 and niraparib [ Time Frame: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months ]
3. Peak plasma concentration of SYD985 and niraparib [ Time Frame: Baseline, Days 1,8,15 of Cycle 1, Days 1,8,15 of Cycle 2, Day 1 of subsequent cycles up to 6 months ]
4. Change from baseline in hematology and blood chemistry parameters [ Time Frame: Baseline and every cycle up to 2 years ]
5. Number of patients with antibodies against SYD985 [ Time Frame: Baseline and every cycle up to 2 years ]
6. Objective response rate [ Time Frame: Baseline and every two cycles for up to 6 months, subsequent every 4 cycles up to 2 years ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Having been treated with:

  1. DUBA-containing ADCs at any time;
  2. Anthracycline treatment within 8 weeks prior to start of study treatment;
  3. 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;
  4. 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);
  5. 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.

Contacts and Locations

Locations

Belgium

University Hospital Antwerp, BE

Antwerp, Belgium, 2650

Institut Jules Bordet

Brussel, Belgium, 1000

Netherlands

Radboud University Medical Center/ NL

Nijmegen, Netherlands, 6500 HB

United Kingdom

The Royal Marsden NHS Foundation Trust

London, United Kingdom, SM2 5PT

The Christie NHS Foundation Trust/ UK

Manchester, United Kingdom, M20 4BX

The Newcastle upon Tyne Hospitals NHS Foundation Trust/UK

Newcastle, United Kingdom, NE7 7DN

Sponsors and Collaborators

Byondis B.V.

Investigators

• Study Director: Norbert Koper; Byondis B.V., The Netherlands

More Information

• Responsible Party: Byondis B.V.
• ClinicalTrials.gov Identifier: NCT04235101
• Other Study ID Numbers: SYD985.004
• First Posted: January 21, 2020
• Last Update Posted: May 16, 2023
• Last Verified: May 2023

Individual Participant Data (IPD) Sharing Statement:

• 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.:

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

Additional relevant MeSH terms:

Neoplasms; Trastuzumab; Niraparib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action