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

NCT04602117 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: ISPY-P1.01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HER2-positive Breast Cancer; HER2 Low; SYD985; Vic-trastuzumab Duocarmazine; Metastatic Cancer; Metastatic Breast Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic; HER2 Low Breast Cancer; GastroEsophageal Cancer; Gastroesophageal Adenocarcinoma; Endometrium Tumor; Ovarian Cancer; Ovarian Carcinoma; HER2-positive Gastric Cancer; HER2-positive Metastatic Breast Cancer; HER2 Mutation-Related Tumors; HER-2 Protein Overexpression; HER2 Low HR Positive; HR Positive; Hormone Receptor-positive Breast Cancer; Estrogen Receptor Positive Tumor; Progesterone Receptor-positive Breast Cancer; Triple Negative Breast Cancer; Hormone Receptor Negative Breast Carcinoma; Bladder Cancer

Keywords

I-SPY Trials; De-escalation; Quantum Leap Healthcare Collaborative; QLHC; ADC; SYD985

Outcome Measures

Primary Outcomes (3)

• 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)

  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

  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

  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

  up to 12 months

• Duration of response (DOR) of patients treated with the weekly paclitaxel with tri-weekly trastuzumab duocarmazine (SYD985) combination

  up to 12 months

Study Arms (1)

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.

Drug: Vic-trastuzumab duocarmazine (SYD985) + paclitaxel

Interventions

Vic-trastuzumab duocarmazine (SYD985) + paclitaxel DRUG

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.

Also known as: SYD985, paclitaxel, SYD-985, Taxol, [vic-] trastuzumab duocarmazine

Vic-trastuzumab duocarmazine (SYD985) + paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Gender: Men and women (premenopausal and postmenopausal)
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• QuantumLeap Healthcare Collaborative: lead
• Byondis B.V.: collaborator

Study Sites (1)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms; Triple Negative Breast Neoplasms; Urinary Bladder Neoplasms

Interventions

trastuzumab duocarmazine; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Paula R Pohlmann, MD, MSc, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Anthony Elias, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 26, 2020
• Study Start: July 28, 2021
• Primary Completion: November 17, 2021
• Study Completion: November 17, 2021
• Last Updated: November 18, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)