Clinical Trials /

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

NCT04235101

Description:

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.

Related Conditions:
  • Breast Carcinoma
  • Endometrial Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Uterine Carcinosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of SYD985 With Niraparib in Patients With Solid Tumors
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: SYD985.004
  • NCT ID: NCT04235101

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
SYD985 + Niraparib(vic-)trastuzumab duocarmazine + ZejulaSYD985 + Niraparib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
SYD985 + NiraparibExperimentalSYD985, 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.
  • SYD985 + Niraparib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicities
Time Frame:21 days
Safety Issue:
Description:First cycle

Secondary Outcome Measures

Measure:Number of patients with adverse events
Time Frame:up to 2 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Change from baseline in hematology and blood chemistry parameters
Time Frame:Baseline and every cycle up to 2 years
Safety Issue:
Description:
Measure:Number of patients with antibodies against SYD985
Time Frame:Baseline and every cycle up to 2 years
Safety Issue:
Description:
Measure:Objective response rate
Time Frame:Baseline and every two cycles for up to 6 months, subsequent every 4 cycles up to 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Byondis B.V.

Trial Keywords

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

Last Updated

June 24, 2020