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

NCT04561362 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BT8009-100
• Study Type: interventional
• Target: 329
• Locations: 6 countries
• Sites: 24

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).

Conditions

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

Keywords

Nectin-4; Solid tumor; Transitional urothelial carcinoma; Renal insufficiency

Outcome Measures

Primary Outcomes (8)

• 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 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

• 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

• 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 Outcomes (21)

• 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.

  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)

• Part B: Duration of Response time to assess preliminary anti-tumor activity of 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: Clinical benefit rate to assess the clinical activity of BT8009 as a monotherapy or in combination with pembrolizumab

  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

• Part B: Progression-free survival time to assess the clinical activity of 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

  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

Study Arms (13)

Part A-1 -BT8009 Monotherapy Dose Escalation

EXPERIMENTAL

Participants will receive escalating doses of BT8009.

Drug: BT8009

Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation

EXPERIMENTAL

Participants will receive BT8009 and a standard dose of pembrolizumab.

Drug: BT8009; Drug: Pembrolizumab

Cohort B-1 - BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Cohort B-2- BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Cohort B-3- BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009. .

Drug: BT8009

Cohort B-4- BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Cohort B-5- BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Cohort B-6- BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009 and standard dose of pembrolizumab.

Drug: BT8009; Drug: Pembrolizumab

Part C - Renal Insufficiency BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Part D - BT8009 Monotherapy Supplementary PK

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Part B-8 - BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Part B-9 - BT8009 Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive a selected dose of BT8009.

Drug: BT8009

Interventions

BT8009 DRUG

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.

Cohort B-1 - BT8009 Monotherapy Dose Expansion; Cohort B-2- BT8009 Monotherapy Dose Expansion; Cohort B-3- BT8009 Monotherapy Dose Expansion; Cohort B-4- BT8009 Monotherapy Dose Expansion; Cohort B-5- BT8009 Monotherapy Dose Expansion; Cohort B-6- BT8009 Monotherapy Dose Expansion; Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion; Part A-1 -BT8009 Monotherapy Dose Escalation; Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation; Part B-8 - BT8009 Monotherapy Dose Expansion; Part B-9 - BT8009 Monotherapy Dose Expansion; Part C - Renal Insufficiency BT8009 Monotherapy Dose Expansion; Part D - BT8009 Monotherapy Supplementary PK

Pembrolizumab DRUG

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.

Also known as: Keytruda

Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion; Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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-8 and B-9: Prior treatment with an ADC containing an MMAE (vedotin) payload.

Sponsors & Collaborators

• BicycleTx Limited: lead

Study Sites (24)

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Ocala Oncology Center

Ocala, Florida, 34474, United States

Location

Advent Health

Orlando, Florida, 34747, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Health Network, Princess Margaret Cancer Centre

Toronto, Ontario, M5G IZ5, Canada

Location

Institut Bergonie

Bordeaux, 33076, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Paoli-Calmettes

Marseille, 13009, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Vall d'Hebron Institute of Oncology

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

START Madrid Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Next Oncology - Hospital Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (2)

• 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 Dec 10;43(35):3728-3738. doi: 10.1200/JCO-25-00559. Epub 2025 Nov 6.

  PMID: 41197088 DERIVED

• 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.

  PMID: 37286457 DERIVED

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Triple Negative Breast Neoplasms; Breast Neoplasms; Ovarian Neoplasms; Renal Insufficiency

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Kidney Diseases

Study Officials

• Meredith McKean, MD, MPH

  Tennessee Oncology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2020
• First Posted: September 23, 2020
• Study Start: July 17, 2020
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 14, 2025

Record last verified: 2025-11

Locations

ES (5); GB (2); CA (1); US (9); IT (2); FR (5)