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

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Neoplasms; Triple Negative Breast Neoplasms; Advanced Solid Tumor; Ovarian Neoplasm; Urinary Bladder Neoplasm; Hormone Receptor Positive, HER2-negative Neoplasms; Hormone Receptor Positive, HER2-low Neoplasms; Non-Small-Cell Lung Neoplasms
• Intervention / Treatment: Drug: Pembrolizumab; Drug: BT8009

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
• Enrollment (Estimated): 329
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G IZ5
      • University Health Network, Princess Margaret Cancer Centre
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13009
    • Institut Paoli-Calmettes
  • Rennes, France, 35042
    • Centre Eugene Marquis
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele
  • MI
    • Milan, MI, Italy, 20133
      • Fondazione IRCCS Istituto Nazionale dei Tumori
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
  • Madrid, Spain, 28040
    • Start Madrid Fundacion Jimenez Diaz
  • Pozuelo de Alarcón, Spain, 28223
    • NEXT Oncology - Hospital Quironsalud Madrid
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute at HealthONE
  • Florida
    • Ocala, Florida, United States, 34474
      • Ocala Oncology Center
    • Orlando, Florida, United States, 34747
      • Advent Health
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University, Sidney Kimmel Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation; Participants will receive BT8009 and a standard dose of pembrolizumab.	Drug: Pembrolizumab; Participants in Cohorts A-2 and B-7 will receive 200 mg IV over 30-minute infusion of pembrolizumab on Day 1 of each Q3W.; Other Names: Keytruda; Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-1 - BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-2- BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-3- BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009. .	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-4- BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-5- BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-6- BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion; Participants will receive a selected dose of BT8009 and standard dose of pembrolizumab.	Drug: Pembrolizumab; Participants in Cohorts A-2 and B-7 will receive 200 mg IV over 30-minute infusion of pembrolizumab on Day 1 of each Q3W.; Other Names: Keytruda; Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Part C - Renal Insufficiency BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Part D - BT8009 Monotherapy Supplementary PK; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Part B-8 - BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Part B-9 - BT8009 Monotherapy Dose Expansion; Participants will receive a selected dose of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.
Experimental: Part A-1 -BT8009 Monotherapy Dose Escalation; Participants will receive escalating doses of BT8009.	Drug: BT8009; Bicyclic Toxin Conjugate (BTC) administered either weekly (i.e., on Days 1, 8, 15, and 22) or biweekly (Days 1 and 15) on a 28-day cycle or on Days 1 and 8 of a 21-day cycle for participants in A-1. Participants in Cohorts A-2 and B-7 will receive BT8009 weekly on 21-day cycle. Participants in Parts B-1-B-6 will receive BT8009 weekly either on a 21-day or 28-day cycle. Participants in Parts B-8 and B-9 will receive BT8009 on Days 1 and 8 of a 21-day cycle. Participants in Cohort C will receive BT8009 once weekly (i.e., on Days 1, 8, 15, and 22) on a 28-day cycle. Participants in Part D will receive BT8009 once weekly on a 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts A-1, A-2 and C: Number of participants with treatment emergent adverse events, receiving BT8009 as a monotherapy or in combination with pembrolizumab to assess safety and tolerability.	Safety reported as incidence of treatment-emergent adverse events using CTCAE v5.0 criteria.	From cycle 1 day 1 until 30 days after the end of treatment or approximately 1 year
Parts A-1 and A-2 (escalations): Number of participants with dose limiting toxicities on BT8009 as a monotherapy or in combination with pembrolizumab	Number of patients who experience dose limiting toxicities BT8009 when given as a monotherapy or in combination with pembrolizumab.	28 days (for cycles that are either 21 or 28 days in length depending on dosing schedule assigned)
Part D: Maximum plasma concentration (Cmax) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone.	From Cycle 1 Day 1 through end of treatment or for up to 1 year
Part D: Minimum plasma concentration (Cmin) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone	From Cycle 1 Day 1 through end of treatment or for up to 1 year
Part D: Area under the plasma concentration-time curve (AUC) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone.	From Cycle 1 Day 1 through end of treatment or for up to 1 year
Part D: Elimination half-life (t1/2) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone.	From Cycle 1 Day 1 through end of treatment or for up to 1 year
Part B1-B7: Objective response rate (ORR) to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab using RECIST 1.1.	Proportion of participants with confirmed complete response or partial response to BT8009 as a monotherapy or in combination with pembrolizumab according to RECIST 1.1 criteria.	Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or, death, or up to three years
PartsB-8, B-9: Number of participants with treatment emergent adverse events receiving an alternative dosing regimen of BT8009 monotherapy to assess safety and tolerability.	Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving an alternative dose regimen of BT8009 as a monotherapy who experience treatment-emergent adverse events using CTCAE v5.0 criteria.	From cycle 1 day 1 until at least 30 days after the end of treatment (each cycle is 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Duration of Response time to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab	Duration of objective response (complete or partial response) by RECIST 1.1 in participants receiving BT8009 as a monotherapy or in combination with pembrolizumab	Every 8 weeks for 12 months then every 12 weeks thereafter until disease progression or, death, or up to three years
Part B: Progression-free survival time to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab.	The time from the first day of study drug administration (Day 1) to disease progression according to RECIST 1.1 criteria in participants receiving BT8009 as a monotherapy or in combination with pembrolizumab.	Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years
Part B: Overall survival time to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab using RECIST 1.1	The time from start of study drug administration (Day 1) until death due to any cause in participants receiving BT8009 as a monotherapy or in combination with pembrolizumab.	Every 8 weeks for the first 12 months then every 12 weeks until death, then every 3 months for up to 1 year after last patient accrued
Cohorts B-4, B-5, and B-6: Objective response rate by Nectin-4 status of BT8009 as a monotherapy in patients with selected solid tumor using RECIST 1.1.	Proportion of participants with confirmed complete response or partial response to BT8009 as a monotherapy according to RECIST 1.1 criteria categorized by Nectin-4 expression status.	Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years
Part C: Maximum plasma concentration (Cmax) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy.	Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part C: Minimum plasma concentration (Cmin) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherap.	Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part C: Area under the plasma concentration-time curve (AUC) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy.	Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part C: Elimination half-life (t1/2) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy.	Plasma concentrations (for impact of renal impairment) of BT8009 and MMAE from Part C participants taking BT8009 as a monotherapy.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
All cohorts: Number of participants positive for anti-drug antibodies (ADA) to determine incidence of ADA	Number of participants positive for anti-drug antibodies (ADA) from all participants receiving BT8009 as a monotherapy or in combination with pembrolizumab	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Parts A-1, A-2, C and D: Duration of Response time to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab.	Duration of objective response (complete or partial response) by RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as a monotherapy or in combination with pembrolizumab.	Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death or up to three years
Parts A-1, A-2, C and D: Overall survival time (months) to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab.	The time from start of study drug administration until death due to any cause in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as a monotherapy or in combination with pembrolizumab.	Every 8 weeks for the first 12 months then every 12 weeks until disease progression, then every 3 months for up to 1 year after last patient is accrued
Part A, B and C: Maximum plasma concentration (Cmax) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab.	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part A, B and C: Minimum plasma concentration (Cmin) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab.	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part A, B and C: Area under the plasma concentration-time curve (AUC) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab.	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part A, B and C: Elimination half-life (t1/2) of BT8009 and monomethyl auristatin E (MMAE) when given as monotherapy and in combination with pembrolizumab.	Plasma concentrations of BT8009 and MMAE from all participants taking BT8009 alone and in combination with pembrolizumab.	From Cycle 1 Day 1 through end of treatment or for up to 1 year (Cycles are 21 days or 28 days depending on the assigned dosing schedule)
Part D: Number of participants with treatment emergent adverse events receiving BT8009 as a monotherapy to assess safety and tolerability in participants with normal renal function or mild renal insufficiency.	Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving BT8009 with normal renal function or mild renal insufficiency who experience treatment-emergent adverse events using CTCAE v5.0 criteria.	From cycle 1 day 1 until at least 30 days after the end of treatment
Parts B-1-B-7: Number of participants with treatment emergent adverse events receiving BT8009 as a monotherapy or in combination with pembrolizumab to assess safety and tolerability.	Number of participants with advanced solid tumor malignancies associated with Nectin-4 expression receiving BT8009 as a monotherapy or in combination with pembrolizumab who experience treatment-emergent adverse events using CTCAE v5.0 criteria.	From cycle 1 day 1 until at least 30 days after the end of treatment (each cycle is 21 or 28 days depending on the assigned dosing schedule)
Parts A-1, A-2, B-8, B-9, and C: Objective response rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab.	Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency with confirmed complete response or partial response according to RECIST 1.1 criteria	Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death or up to three years
Parts A-1, A-2, C and D: Clinical benefit rate to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab	Proportion of participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency who have complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks according to the RECIST Version 1.1 criteria.	Every 8 weeks for the first 12 months then every 12 weeks until disease progression for up to 3 years
Parts A-1, A-2, C and D: Progression-free survival time (months) to assess preliminary anti-tumor activity of BT8009 as a monotherapy or in combination with pembrolizumab	The time from start of study drug administration until disease progression according to RECIST 1.1 in participants with advanced solid tumor malignancies associated with Nectin-4 expression or advanced solid tumor malignancies having renal insufficiency receiving BT8009 as a monotherapy or in combination with pembrolizumab.	Every 8 weeks for the first 12 months then every 12 weeks until disease progression or death for up to three years
Part B: Clinical benefit rate to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab	Proportion of participants who have complete response (CR), partial response (PR), or stable disease (SD) for at least 16 weeks according to RECIST Version 1.1 criteria.	Every 8 weeks Parts A-1, A-2, and C) and every 9 weeks (cohorts B-8 and B-9) for 12 months then every 12 weeks thereafter until disease progression or death or up to 3 years

Collaborators and Investigators

• Sponsor: BicycleTx Limited
• Investigators: Study Chair: Meredith McKean, MD, MPH, Tennessee Oncology

Publications and helpful links

General Publications

• Klumper N, Eckstein M, Holzel M, Herrmann K, Hadaschik B, Grunwald V. Re: First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma: Navigating Metastatic Urothelial Cancer with Nectin-4 PET/CT. Eur Urol. 2023 Nov;84(5):514-515. doi: 10.1016/j.eururo.2023.05.029. Epub 2023 Jun 5. No abstract available.
• Baldini C, Verlingue L, Goldschmidt V, Doger de Speville B, Lostes J, Italiano A, Cousin S, Falchook GS, Necchi A, Reig Torras O, Fontana E, Carter L, Rodon Ahnert J, Brown JR, DeMars LR, Josephs K, Dickson A, Xu C, Bader J, Campbell C, Sharma R, McKean M. First-in-Human, Phase I/II Dose Escalation and Expansion Study of Zelenectide Pevedotin in Patients With Advanced Solid Tumors: Results From Monotherapy Dose Escalation. J Clin Oncol. 2025 Nov 6:JCO2500559. doi: 10.1200/JCO-25-00559. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2020
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 14, 2020
• First Submitted That Met QC Criteria: September 22, 2020
• First Posted (Actual): September 23, 2020

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Solid tumor; Renal insufficiency; Nectin-4; Transitional urothelial carcinoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Skin and Connective Tissue Diseases; Ovarian Neoplasms; Breast Neoplasms; Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; pembrolizumab
• Other Study ID Numbers: BT8009-100

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No