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NCT04561362 | RECRUITING | Urinary Bladder Neoplasm

Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Malignancies
Sponsor:

BicycleTx Limited

Brief Summary:

This study is a Phase I/II, multicenter, first-in-human, open-label dose-escalation study of BT8009 given as a single agent and in combination with pembrolizumab in participants with advanced solid tumors associated with Nectin-4 expression or in participants with advanced solid tumor malignancies having renal insufficiency. The primary endpoints are: Dose limiting toxicities (Parts A-1 and A-2), Overall response rate per RECIST v1.1 (Parts B1-B7), Safety and tolerability (Parts B-8, B-9 and C), and characterization of the pharmacokinetics (Part D).

Condition or disease

Urinary Bladder Neoplasm

Triple Negative Breast Neoplasms

Hormone Receptor Positive, HER2-negative Neoplasms

Hormone Receptor Positive, HER2-low Neoplasms

Breast Neoplasms

Non-Small-Cell Lung Neoplasms

Ovarian Neoplasm

Advanced Solid Tumor

Intervention/treatment

BT8009

Pembrolizumab

Phase

PHASE1

PHASE2

Detailed Description:

This study will assess the safety and tolerability of BT8009 alone and in combination with pembrolizumab in patients with select advanced solid tumors. BT8009 will be given as a single agent in 3 different dosing schedules- weekly (28 day cycle), biweekly (28 day cycle) or dosing on day 1 and day 8 of a 3-weekly (21 day cycle) and in combination with pembrolizumab. There are four parts to this study. Part A is a dose escalation in patients with select advanced solid tumors primarily designed to evaluate safety and tolerability of BT8009 as monotherapy or in combination with pembrolizumab and to determine a recommended Phase II dose (RP2D). Following a selection of an RP2D, Part B, a dose expansion portion, will be initiated with the primary objective of clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab in patients with select advanced solid tumors. Additionally Parts B-8 and B-9 will evaluate the safety and tolerability of an alternate dose and schedule of BT8009 monotherapy. Part C will evaluate safety and tolerability of RP2D in patients with renal insufficiency. Part D will further characterize the pharmacokinetics of BT8009 and MMAE.

Study Type : INTERVENTIONAL
Estimated Enrollment : 329 participants
Masking : NONE
Primary Purpose : TREATMENT
Official Title : Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies
Actual Study Start Date : 2020-07-17
Estimated Primary Completion Date : 2026-12
Estimated Study Completion Date : 2026-12

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
Criteria
Key Inclusion Criteria
  • * Life expectancy ≥12 weeks.
  • * Patients must have measurable disease per RECIST 1.1.
  • * Part A-1 cohorts:
  • * Must have exhausted all standard treatment options, including appropriate targeted therapies; or patients for which no standard therapy is considered appropriate
  • * Patients with advanced, histologically confirmed urothelial (transitional cell) carcinoma that recurred after or has been refractory to prior therapy (fresh tumor biopsy or an archived sample must be submitted); or
  • * Patients with advanced, histologically confirmed pancreatic, breast, non-small-cell lung cancer (NSCLC), gastric, esophageal, head and neck, or ovarian tumors that recurred after or has been refractory to prior therapy (fresh tumor biopsy or an archived sample testing for Nectin-4 expression).
  • * Part A-2:
  • * Must have exhausted all standard treatment options, including appropriate targeted therapies; or patients for which no standard therapy is considered appropriate
  • * Patients with advanced, histologically confirmed urothelial (transitional cell) carcinoma that have progressed following prior therapy
  • * Cohort B-1: Histologically documented urothelial carcinoma, previously treated with enfortumab vedotin (EV). Patients with resectable, locally advanced urothelial carcinoma are ineligible. Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
  • * Cohort B-2 and B-3: Histologically documented urothelial carcinoma, not previously treated with enfortumab vedotin (EV). Patients with resectable, locally advanced urothelial carcinoma are ineligible. Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
  • * Cohort B-4: Patients with histologically confirmed non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer that is Stage III or IV according to the International Federation of Gynecology and Obstetrics (FIGO) or tumor, node and metastasis staging criteria that have progressed following prior therapy.
  • * Cohort B-5: Patients with triple-negative breast cancer confirmed negative for estrogen receptor (ER) and progesterone receptor (PR) and negative for human epidermal growth factor receptor 2 (HER2) (i.e., triple-negative) that have progressed following prior therapy.
  • * Cohort B-6: Patients with histologically confirmed non-small cell lung cancer (NSCLC) with no actionable mutations, such as Epidermal Growth Factor Receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) fusion oncogene, or ROS1 that have progressed following prior therapy.
  • * Cohort B-7: Locally advanced or metastatic, histologically confirmed urothelial (transitional cell) carcinoma, ineligible for cisplatin, no prior systemic anticancer treatment for advanced urothelial carcinoma.
  • * Cohort B-8: Locally advanced (unresectable) or metastatic, histologically confirmed breast cancer, either TNBC or hormone receptor (HR) positive and HER-2 negative according to ASCO/CAP guidelines and up to 3 prior lines of therapy for advanced (unresectable) or metastatic disease.
  • * Cohort B-9: Histologically confirmed advanced/metastatic squamous or non-squamous NSCLC, negative for oncogenic driver mutations (EGFR, KRAS, ALK, BRAF, MET, ERRB2).
  • * Cohort C renal insufficiency cohort: Patients with histologically documented urothelial carcinoma, ovarian, triple negative breast, or non-small cell lung cancer that have been previously treated with a locally approved therapy.
  • * Part D supplementary PK: Patients must have histologically confirmed urothelial (transitional cell) carcinoma (patients with squamous differentiation or mixed cell types are eligible); ovarian; triple-negative breast; or non-small cell lung cancer that have been previously treated with a locally approved therapy.
  • Key Exclusion Criteria (all patients)
    • * Clinically relevant troponin elevation
    • * Uncontrolled diabetes
    • * Known active or untreated CNS and/or carcinomatous meningitis
    • * Grade ≥2 peripheral neuropathy
    • * Active keratitis or corneal ulcerations
    • * Patients with uncontrolled hypertension
    • * History of another malignancy within 3 years before first dose of BT8009 or residual disease from a previously diagnosed malignancy (with some exceptions).
    • * Active systemic infection requiring therapy, or fever within the last 14 days prior to first dose of BT8009.
    • * Prior Stevens-Johnson syndrome/toxic epidermal necrolysis on any MMAE-conjugated drug
    • * Parts A-2 and B-7 Pembrolizumab Combination Cohorts:
    • * Prior organ transplant (including allogeneic)
    • * Diagnosis of clinically relevant immunodeficiency
    • * History of interstitial lung disease
    • * Parts B-2 and B-3: Prior treatment with enfortumab vedotin Other protocol-defined Inclusion/Exclusion criteria may apply
    • * Parts B-8 and B-9: Prior treatment with an ADC containing an MMAE (vedotin) payload.
    • Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Malignancies

    Location Details

    NCT04561362

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    How to Participate

    Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

    Locations

    RECRUITING

    United States, Colorado

    Sarah Cannon Research Institute at HealthONE

    Denver, Colorado, United States, 80218

    RECRUITING

    United States, Florida

    Ocala Oncology Center

    Ocala, Florida, United States, 34474

    RECRUITING

    United States, Florida

    Advent Health

    Orlando, Florida, United States, 34747

    WITHDRAWN

    United States, Indiana

    Horizon Oncology Research

    Lafayette, Indiana, United States, 47905

    WITHDRAWN

    United States, Kentucky

    Norton Cancer Institute, Downtown

    Louisville, Kentucky, United States, 40207

    WITHDRAWN

    United States, Nevada

    Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, United States, 89169

    RECRUITING

    United States, New York

    Icahn School of Medicine at Mount Sinai

    New York, New York, United States, 10029

    RECRUITING

    United States, Ohio

    University Hospitals Cleveland Medical Center

    Cleveland, Ohio, United States, 44106

    RECRUITING

    United States, Pennsylvania

    Thomas Jefferson University, Sidney Kimmel Cancer Center

    Philadelphia, Pennsylvania, United States, 19107

    RECRUITING

    United States, Tennessee

    Tennessee Oncology, PLLC

    Nashville, Tennessee, United States, 37203

    RECRUITING

    United States, Texas

    Mary Crowley Cancer Research Center

    Dallas, Texas, United States, 75230

    RECRUITING

    United States, Texas

    The University of Texas MD Anderson Cancer Center

    Houston, Texas, United States, 77030

    WITHDRAWN

    Canada, Alberta

    Cross Cancer Institute

    Edmonton, Alberta, Canada, T6G 1Z2

    RECRUITING

    Canada, Ontario

    University Health Network, Princess Margaret Cancer Centre

    Toronto, Ontario, Canada, M5g out 5

    RECRUITING

    France,

    Institute of Bergonie

    Bordeaux, France, 33076

    RECRUITING

    France,

    Center Leon Berard

    Lyon, France, 69373

    RECRUITING

    France,

    Institut Paoli-Calmettes

    Marseille, France, 13009

    RECRUITING

    France,

    Centre Eugene Marquis

    Rennes, France, 35042

    RECRUITING

    France,

    Gustave Roussy Institute

    Villejuif, France, 94805

    RECRUITING

    Italy, MI

    IRCCS Foundation National Cancer Institute

    Milano, MI, Italy, 20133

    RECRUITING

    Italy,

    San Raffaele Hospital

    Milan, Italy, 20132

    RECRUITING

    Spain,

    Vall d'Hebron Institute of Oncology

    Barcelona, Spain, 08035

    RECRUITING

    Spain,

    Clinic Hospital in Barcelona

    Barcelona, Spain, 08036

    RECRUITING

    Spain,

    START MADRID JIMANEZ DIAZ FOUNDATION

    Madrid, Spain, 28040

    RECRUITING

    Spain,

    La Paz University Hospital

    Madrid, Spain, 28046

    RECRUITING

    Spain,

    Next Oncology - Hospital Quironsalud Madrid

    Pozuelo de Alarcon, Spain, 28223

    RECRUITING

    Spain,

    Marques de Valdecilla University Hospital

    Santander, Spain, 39008

    RECRUITING

    United Kingdom,

    Sarah Cannon Research Institute UK

    London, United Kingdom, W1G 6AD

    RECRUITING

    United Kingdom,

    The Christie NHS Foundation Trust

    Manchester, United Kingdom, M20 4BX