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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 : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Synthon Biopharmaceuticals BV

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
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.
Estimated Study Start Date : March 2020
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Incidence of Treatment-Emergent Adverse Events (AEs) [ Time Frame: 2 years ]
    AEs will be graded by the investigator as assessed by CTCAE v5.0.



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04235101


Contacts
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Contact: Norbert Koper +31 24 372 7700 clinicaltrials@synthon.com

Sponsors and Collaborators
Synthon Biopharmaceuticals BV
Investigators
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Study Director: Norbert Koper Synthon Biopharmaceuticals BV, The Netherlands

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Responsible Party: Synthon Biopharmaceuticals BV
ClinicalTrials.gov Identifier: NCT04235101    
Other Study ID Numbers: SYD985.004
First Posted: January 21, 2020    Key Record Dates
Last Update Posted: January 21, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Synthon Biopharmaceuticals BV:
Solid Tumor
Anti-body Drug Conjugate
ADC
niraparib
Additional relevant MeSH terms:
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Neoplasms
Niraparib
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action