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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04235101
Recruitment Status : Not yet recruiting
First Posted : January 21, 2020
Last Update Posted : April 3, 2020
Sponsor:
Information provided by (Responsible Party):
Synthon Biopharmaceuticals BV

Tracking Information
First Submitted Date  ICMJE January 16, 2020
First Posted Date  ICMJE January 21, 2020
Last Update Posted Date April 3, 2020
Estimated Study Start Date  ICMJE June 2020
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
Objective Response Rate (ORR) [ Time Frame: 2 years ]
Objective response rate is defined as the proportion of patients with an assessed best overall response of complete response or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2020)
  • Progression-Free Survival (PFS) [ Time Frame: 2 years ]
    Progression-free survival is defined as the time from the date of randomization to the date of first documented disease progression by investigator assessment according to RECIST v1.1 or death due to any cause, whichever occurred earlier.
  • Overall Survival (OS) [ Time Frame: 2-year overall survival ]
    Overall survival is defined as the time from date of randomization to death due to any cause.
  • Incidence of Treatment-Emergent Adverse Events (AEs) [ Time Frame: 2 years ]
    AEs will be graded by the investigator as assessed by CTCAE v5.0.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors
Official Title  ICMJE 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.
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: SYD985 + Niraparib
SYD985 powder for concentrate for solution for infusion Niraparib 100 mg per hard capsule
Other Name: (vic-)trastuzumab duocarmazine + Zejula
Study Arms  ICMJE 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.
Intervention: Drug: SYD985 + Niraparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 16, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Norbert Koper +31 24 372 7700 clinicaltrials@synthon.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04235101
Other Study ID Numbers  ICMJE SYD985.004
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Synthon Biopharmaceuticals BV
Study Sponsor  ICMJE Synthon Biopharmaceuticals BV
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Norbert Koper Synthon Biopharmaceuticals BV, The Netherlands
PRS Account Synthon Biopharmaceuticals BV
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP