ISPY-P1.01:Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer

  • End date
    Dec 1, 2022
  • participants needed
  • sponsor
    QuantumLeap Healthcare Collaborative
Updated on 5 November 2021
platelet count
tubal ligation
monoclonal antibodies
measurable disease
breast cancer
growth factor
endocrine therapy
cytotoxic chemotherapy
neutrophil count
hormone therapy
epidermal growth factor receptor
cancer chemotherapy
parp inhibitor
epidermal growth factor
Accepts healthy volunteers


This is an open-label, single-arm, multi-site phase I/Ib 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 a 3+3 de-escalation cohort. Participants with certain HER-positive advanced solid tumors or HER2-low breast cancer will be enrolled in this cohort. Eligible participants will receive infusions of SYD985 every three weeks and of paclitaxel weekly. Participants will be monitored for safety and for the occurance of DLTs. Cohort B dose expansion will proceed at the identified dose from Cohort A (RP2D). Cohort B will only enroll patients with HER2-positive or HER2-low breast cancer.

Condition Brain Metastases, Urothelial Cancer, Epithelial Ovarian Carcinoma, Endometrial Carcinoma, SYD985, HER2 Low Breast Cancer, HER2 Low, urinary tract neoplasm, ovarian epithelial carcinoma, Cancer, Metastatic, metastatic tumor, Metastatic Cancer, bladder cancer, metastatic qualifier, Bladder Carcinoma, Vic-trastuzumab Duocarmazine, Metastasis, Recurrent Ovarian Cancer, Gastroesophageal Cancer, carcinoma of the bladder, HER2 Positive Gastric Cancer, Gastroesophageal Adenocarcinoma, bladder tumor, metastatic disease, secondaries, Urologic Cancer, Neoplasm Metastasis, Triple Negative Breast Cancer, cancer of the ovary, Estrogen Receptor Positive Tumor, HER2 Positive Metastatic Breast Cancer, Metastatic Gastrointestinal Carcinoid Tumor, metastases, HER2 Mutation-Related Tumors, Breast Cancer, Urothelial Carcinoma, cancer ovarian, ovarian carcinoma, Urothelial Tumor, HER-2 Protein Overexpression, metastasized, her2-positive breast cancer, ovarian carcinomas, Hormone Receptor Positive Breast Cancer, ovarian tumors, HR Positive, Bone Metastases, Bladder Disorders, Ovarian Function, SYD-985, carcinoma of the ovary, Transitional cell carcinoma, Metastatic Breast Cancer, Bladder Cancer, Ovarian Cancer, secondary cancer, HER2 Low HR Positive, Hormone Receptor Negative Breast Carcinoma, cancer, ovarian, Progesterone Receptor Positive Breast Cancer, Liver Metastases, cancers metastatic, her2/neu-positive breast cancer, bladder disorder, Ovarian disorder, HER2 Positive Breast Cancer, Stage IV Breast Cancer, Endometrial Cancer
Treatment Vic-trastuzumab duocarmazine (SYD985), Vic-trastuzumab duocarmazine (SYD985) + paclitaxel
Clinical Study IdentifierNCT04602117
SponsorQuantumLeap Healthcare Collaborative
Last Modified on5 November 2021


Yes No Not Sure

Inclusion Criteria

Signed informed consent and for collection of archival FFPE blocks (freshly cut 14 unstained tumor slides would be acceptable) obtained prior to any study specific assessments and procedures
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
HER2 POSITIVE: breast, gastroesophageal adenocarcinoma, colorectal, ovarian, endometrial and urothelial tumors
HER2 LOW: breast (irrespective of HR status)
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: Breast HER2 pos
Prior treatment lines allowed
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
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
Cohort A (de-escalation)
HR neg
No more than 2 lines of systemic cytotoxic therapy for advanced/metastatic disease; antibody drug conjugate counts as cytotoxic therapy
Cohort B (expansion)
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 4 lines of anti-HER2 therapy for advanced/ metastatic disease
Other histology: colorectal, ovarian, endometrial and urothelial
No more than 2 lines of systemic cytotoxic therapy for advanced/metastatic disease
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)
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
No more than 2 lines of systemic cytotoxic therapy
ECOG performance status 0-2 (Appendix E: ECOG PS scale)
Adequate organ function, evidenced by the following laboratory results

Exclusion Criteria

Wash out periods: Other anticancer therapy as below within the following period
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
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
Anthracycline treatment within 3 months prior to start IMP treatment
chemotherapy or investigational agents, 3 weeks
MAbs and immunotherapy, 4 weeks
mitomycin C and nitrosoureas, 6 weeks
Concurrent therapy with other Investigational Products
radiotherapy, 4 weeks
targeted therapy and endocrine therapy, 2 weeks
Recent major surgery within 4 weeks prior to start IMP treatment
Pregnancy or lactation
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