HER2-positive Breast CancerPhase 1NCT04602117

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

A Phase 1 study testing Vic-trastuzumab duocarmazine (SYD985) + paclitaxel in people with HER2-positive Breast Cancer and HER2 Low, run by QuantumLeap Healthcare Collaborative at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: HER2-positive Breast Cancer, HER2 Low, SYD-985
What is being tested?: Vic-trastuzumab duocarmazine (SYD985) + paclitaxel
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 28 Jul 2021to 17 Nov 2021
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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..
Cohort A (de-escalation):
HER2 POSITIVE: breast, gastroesophageal adenocarcinoma, colorectal, ovarian, endometrial and urothelial tumors
HER2 LOW: breast (irrespective of HR status)

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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: 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.
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.

Who cannot join

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

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Colorado Cancer Center
Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: ISPY-P1.01: Evaluating the Safety of Weekly Paclitaxel With Trastuzumab Duocarmazine (SYD985) in Patients With Metastatic Cancer: A Phase I/Ib Trial

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.

Read the detailed description

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.

Conditions: HER2-positive Breast Cancer, HER2 Low, SYD-985, SYD985, Vic-trastuzumab Duocarmazine, Metastatic Cancer
Being tested: Vic-trastuzumab duocarmazine (SYD985) + paclitaxel
Keywords: I-SPY Trials, De-escalation, Quantum Leap Healthcare Collaborative, QLHC, ADC, SYD985
Medical subject headings: Neoplasm Metastasis, Breast Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Triple Negative Breast Neoplasms, Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vic-trastuzumab duocarmazine (SYD985) + paclitaxelDrug
Also called SYD985, paclitaxel, SYD-985, Taxol
SYD985 ([vic-]trastuzumab duocarmazine) an antibody-drug conjugate or ADC being developed by Byondis B.V. (Nijmegen, The Netherlands), consists of the recombinant humanized anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab linked, via a cleavable linker, to the duocarmycin prodrug, seco-duocarmycin-hydroxybenzamide-azaindole or seco-DUBA, which has potent antineoplastic activity.
Eligible patients will receive infusions of SYD985 every three weeks and of paclitaxel weekly.

Study groups in NCT04602117
Study group	Role	What they receive
Vic-trastuzumab duocarmazine (SYD985) + paclitaxel	Experimental	Single-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. Receives: Drug: Vic-trastuzumab duocarmazine (SYD985) + paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

Common Toxicity Criteria for Adverse Events (CTCAE 5.0)
To determine safety and tolerability of the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination in patients with certain advanced solid tumors
Toxicity, incidence and grade, Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD), Recommended Phase 2 Dose (RP2D)
Measured: up to 12 months
Clinical Benefit Rate (CBR) at 6 months
To obtain Preliminary efficacy data of the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination in patients with certain advanced solid tumors
Outcome measure: RECIST 1.1
Measured: up to 6 months
Overall response rate (ORR)
To obtain Preliminary efficacy data of the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination in patients with certain advanced solid tumors
Outcome measure: RECIST 1.1
Measured: up to 6 months

Secondary outcomes (2)

Progression Free Survival (PFS) of patients treated with the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination
Endpoint: PFS
RECIST 1.1
Measured: up to 12 months
Duration of response (DOR) of patients treated with the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination
Endpoints: Duration of response
Outcome measures:
Measured: up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jul 202117 Nov 2021

First posted26 Oct 2020
Study start28 Jul 2021
Primary completion17 Nov 2021
Study completion17 Nov 2021

Why it stopped: Study withdrawn as scientific interest in pursuing the SYD985+Paclitaxel combination has diminished.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HER2-positive Breast CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: This is an open-label, 3+3 design, single-arm, phase I trial with SYD985, an antibody-drug conjugate (ADC) targeting HER2 on the cell membrane, combined with paclitaxel.
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04602117
Sponsor's protocol ID: ISPY-P1.01
Status last verified: Nov 2023
First submitted: 12 Oct 2020
Last updated: 18 Nov 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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