Clinical Trials /

Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer

NCT04602117

Description:

This is an open-label, single-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Breast Carcinoma
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
  • Malignant Colorectal Neoplasm
  • Malignant Endometrial Neoplasm
  • Malignant Ovarian Neoplasm
  • Malignant Urethral Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer
  • Official Title: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial

Clinical Trial IDs

  • ORG STUDY ID: ISPY-P1.01
  • NCT ID: NCT04602117

Conditions

  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
Vic-trastuzumab duocarmazine (SYD985)SYD985, paclitaxelVic-trastuzumab duocarmazine (SYD985)

Purpose

This is an open-label, single-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel.

Detailed Description

      The study contains 2 cohorts. Cohort A is the de-escalation cohort. Patients with certain
      HER-positive or HER2-low advanced solid tumors will be enrolled in this cohort. Cohort B is
      the expansion cohort, in which only patients with HER2-positive or HER2-low breast cancer
      will be enrolled.
    

Trial Arms

NameTypeDescriptionInterventions
Vic-trastuzumab duocarmazine (SYD985)Experimentalsingle-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel. The study contains 2 cohorts. Cohort A is the de-escalation cohort. Patients with certain HER-positive advanced solid tumors or HER2-low breast cancer will be enrolled in this cohort. Cohort B is the expansion cohort, in which only patients with HER2-positive or HER2-low breast cancer can be enrolled. Treatment will be administered on an outpatient basis.
  • Vic-trastuzumab duocarmazine (SYD985)

Eligibility Criteria

        Inclusion Criteria:

        INCLUSION CRITERIA

        • Signed informed consent and for collection of archival FFPE block (freshly cut 14
        unstained tumor slides would be acceptable) obtained prior to any study specific
        assessments and procedures.

        • Age ≥18 years

        • Gender: Men and women (premenopausal and postmenopausal)

        Histologic diagnosis: Biopsy-proven solid malignancy diagnosis of one of the below
        mentioned types, that is advanced.

        ER, PgR and HER2 measurements should be performed according to institutional guidelines, in
        a CLIA-approved setting, when indicated. Cut-off values for positive/negative staining
        should be in accordance with current ASCO/CAP (American Society of Clinical
        Oncology/College of American Pathologists) guidelines2-4 published in 2017 for
        Gastroesophageal Adenocarcinoma, and in 2018 for breast cancer. For other histologic types,
        HER2 assessment will follow local institutional criteria. Patients with breast cancer and
        equivocal HER2 in situ hybridization results according to current ASCO/CAP guidelines are
        eligible.

        Cohort A (de-escalation):

        HER2 POSITIVE: breast, gastroesophageal adenocarcinoma, colorectal, ovarian, endometrial
        and urothelial tumors HER2 LOW: breast (irrespective of HR status)

        Cohort B (expansion):

        HER2 POSITIVE: breast HER2 LOW: breast (irrespective of HR status)

        • Prior therapy: disease has progressed after at least one line of standard/approved
        therapy in the advanced setting Histology Prior treatment lines allowed Breast HER2 pos
        Must have received at least a taxane and trastuzumab for advanced/metastatic disease.

        Recurrence during or within 6 months of end of adjuvant therapy counts as 1 line.

        No more than 4 lines of anti-HER2 therapy for advanced/ metastatic disease. Trastuzumab
        beyond progression: each chemotherapy regimen combined with trastuzumab counts as a
        separate line also when that regimen is interrupted for any time and any other reason than
        recovery from drug-related toxicity or when chemotherapy is recycled.

        Breast HER2low HR neg (TN) No more than 2 lines of systemic cytotoxic therapy for
        advanced/metastatic disease; antibody drug conjugate counts as cytotoxic therapy.

        No limit number of lines for prior immunotherapy, PI3Kinase/AKT pathway inhibitors or PARP
        inhibitors. However, no more than one PARP inhibitor is allowed.

        Breast HER2low HR pos (ER/PR pos) No more than 2 lines of systemic cytotoxic therapy for
        advanced/metastatic disease; antibody drug conjugate counts as cytotoxic therapy.

        No limit number of lines for endocrine therapy, CDK4/6 inhibitors, PI3Kinase/AKT pathway
        inhibitors, PARP inhibitors or immunotherapy.

        Gastroesophageal adenocarcinoma Must have received at least one prior HER2 targeted therapy
        for advanced/metastatic disease.

        No more than 2 lines of systemic cytotoxic therapy.

        Other histology: colorectal, ovarian, endometrial and urothelial No more than 2 lines of
        systemic cytotoxic therapy for advanced/metastatic disease.

        • ECOG performance status 0-2 (Appendix E: ECOG PS scale).

        • Estimated life expectancy > 12 weeks at the start of investigational medicinal product
        (IMP) treatment.

        • Measurable disease: for Cohort B (expansion) only, at least one measurable cancer lesion
        as defined by the Response Evaluation Criteria for Solid Tumors (RECIST version 1.1);

        •

        Adequate organ function, evidenced by the following laboratory results:

        Absolute neutrophil count ≥ 1,500/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 9.0 g/dL
        with no blood transfusion in the past 28 days Total bilirubin ≤ 1.5 x the upper limit of
        normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x
        ULN (or ≤ 5.0 x ULN in the presence of liver metastases) Serum creatinine within normal
        institutional limits or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with serum
        creatinine levels above institutional ULN.

        • Non-Pregnant: Serum or urine pregnancy test must be negative within 14 days of treatment
        start in women of childbearing potential. Pregnancy testing does not need to be pursued in
        patients who are judged as postmenopausal before enrollment, or who have undergone
        bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation.

        • Contraception: Willingness to undergo adequate contraception if childbearing potential.
        Women of childbearing potential and men must use adequate contraception for the duration of
        protocol treatment and for 6 months after the last treatment with SYD985/paclitaxel.
        Adequate contraception is defined as one highly effective form (i.e. abstinence, (fe)male
        sterilization) OR two effective forms (e.g. non-hormonal IUD and condom / occlusive cap
        with spermicidal foam / gel / film / cream / suppository).

        • Prior therapy effects: Resolution of all acute toxic effects of prior therapy, including
        radiotherapy to grade ≤1 and neuropathy to grade ≤2 (except toxicities not considered a
        safety risk for the patient) and recovery from surgical procedures.

        • Patient compliance: patients who are willing and able to comply with scheduled visits,
        treatment plan, laboratory tests, and other study procedures.

        Exclusion Criteria:

        -

        • Anthracycline treatment within 3 months prior to start IMP treatment.

        • Wash out periods: Other anticancer therapy as below within the following period.

          -  chemotherapy or investigational agents, 3 weeks

          -  mitomycin C and nitrosoureas, 6 weeks

          -  radiotherapy, 4 weeks

          -  targeted therapy and endocrine therapy, 2 weeks

          -  MAbs and immunotherapy, 4 weeks • Concurrent therapy with other Investigational
             Products.

        Trastuzumab hypersensitivity: History of infusion-related reactions and/or hypersensitivity
        to trastuzumab (as antibody or as part of antibody-drug conjugate), trastuzumab emtansine
        or excipients of the study drug which led to permanent discontinuation of the treatment.

        Uncontrolled intercurrent illness including (active infection, diabetes, pulmonary embolism
        in the past 6 months, or psychiatric illness/social situations that would limit compliance
        with study requirements).

        • Cardiovascular disease: History (within 6 months prior to start IMP) of clinically
        significant cardiovascular disease such as unstable angina, congestive heart failure (CHF),
        myocardial infarction, uncontrolled hypertension, cardiac arrhythmia requiring medication,
        or baseline corrected QT by Fridericia's formula (QTcF) length ≥ 450 ms for men and ≥ 470
        ms for women.History (within 6 months prior to start IMP) of clinically significant
        cardiovascular disease such as unstable angina, congestive heart failure (CHF), myocardial
        infarction, uncontrolled hypertension, or cardiac arrhythmia requiring medication.

        • Left ventricular ejection fraction (LVEF) < 50% as assessed by either echocardiography or
        multiple-gated acquisition (MUGA) scan at study screening; or a history of absolute
        decrease in LVEF of ≥ 10% points to < 50% during previous treatment with trastuzumab or
        trastuzumab emtansine, or a history of decrease in LVEF to < 40% during previous treatment
        with trastuzumab or trastuzumab emtansine.

        • Interstitial Lung Disease (ILD): History 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. If lung
        infiltrates are visible other tests such as a breast MRI, additional testing will be
        required to establish possible cause for findings.

        • Eye disease: Keratitis, or other clinically significant corneal disease, diagnosed by an
        ophthalmologist. Exam includes a slit lamp exam and fluorescence tear film break-up time.
        Pachymetry is optionalExam includes a slit lamp exam, corneal sensitivity testing,
        fluorescence tear film break-up time, and pachymetry.

        • CNS tumoral spread: Active uncontrolled/symptomatic central nervous system cancer/spinal
        cord compression. Previously treated and clinically stable lesions, as per Investigator's
        judgment, are permitted.

        • Liver disease: Patients with clinically significant history of liver disease, including
        viral or other known hepatitis, current alcohol abuse, or cirrhosis.

        • Recent major surgery within 4 weeks prior to start IMP treatment

        • Pregnancy or lactation

        • Other condition, which in the opinion of the investigator, would compromise the safety of
        the patient or the patient's ability to complete the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Primary objectives
Time Frame:up to six months
Safety Issue:
Description:Common Toxicity Criteria for Adverse Events (CTCAE 5.0)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:QuantumLeap Healthcare Collaborative

Last Updated

October 20, 2020