Trial Title:
Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Malignancies
NCT ID:
NCT04561362
Condition:
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
Conditions: Official terms:
Neoplasms
Breast Neoplasms
Lung Neoplasms
Ovarian Neoplasms
Urinary Bladder Neoplasms
Triple Negative Breast Neoplasms
Pembrolizumab
Conditions: Keywords:
Nectin-4
Solid tumor
Transitional urothelial carcinoma
Renal insufficiency
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BT8009
Description:
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 a 60-minute IV infusion of
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.
Arm group label:
Cohort B-1 - BT8009 Monotherapy Dose Expansion
Arm group label:
Cohort B-2- BT8009 Monotherapy Dose Expansion
Arm group label:
Cohort B-3- BT8009 Monotherapy Dose Expansion
Arm group label:
Cohort B-4- BT8009 Monotherapy Dose Expansion
Arm group label:
Cohort B-5- BT8009 Monotherapy Dose Expansion
Arm group label:
Cohort B-6- BT8009 Monotherapy Dose Expansion
Arm group label:
Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion
Arm group label:
Part A-1 -BT8009 Monotherapy Dose Escalation
Arm group label:
Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation
Arm group label:
Part B-8 - BT8009 Monotherapy Dose Expansion
Arm group label:
Part B-9 - BT8009 Monotherapy Dose Expansion
Arm group label:
Part C - Renal Insufficiency BT8009 Monotherapy Dose Expansion
Arm group label:
Part D - BT8009 Monotherapy Supplementary PK
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
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.
Arm group label:
Cohort B-7- BT8009 in Combination with Pembrolizumab Dose Expansion
Arm group label:
Part A-2 -BT8009 in Combination with Pembrolizumab Dose De-Escalation
Other name:
Keytruda
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).
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.
Criteria for eligibility:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Sarah Cannon Research Institute at HealthONE
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Facility:
Name:
Ocala Oncology Center
Address:
City:
Ocala
Zip:
34474
Country:
United States
Status:
Recruiting
Facility:
Name:
Advent Health
Address:
City:
Orlando
Zip:
34747
Country:
United States
Status:
Recruiting
Facility:
Name:
Horizon Oncology Research
Address:
City:
Lafayette
Zip:
47905
Country:
United States
Status:
Withdrawn
Facility:
Name:
Norton Cancer Institute, Downtown
Address:
City:
Louisville
Zip:
40207
Country:
United States
Status:
Withdrawn
Facility:
Name:
Comprehensive Cancer Centers of Nevada
Address:
City:
Las Vegas
Zip:
89169
Country:
United States
Status:
Withdrawn
Facility:
Name:
Icahn School of Medicine at Mount Sinai
Address:
City:
New York
Zip:
10029
Country:
United States
Status:
Recruiting
Facility:
Name:
University Hospitals Cleveland Medical Center
Address:
City:
Cleveland
Zip:
44106
Country:
United States
Status:
Recruiting
Facility:
Name:
Thomas Jefferson University, Sidney Kimmel Cancer Center
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Facility:
Name:
Tennessee Oncology, PLLC
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Mary Crowley Cancer Research Center
Address:
City:
Dallas
Zip:
75230
Country:
United States
Status:
Recruiting
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
Cross Cancer Institute
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Status:
Withdrawn
Facility:
Name:
University Health Network, Princess Margaret Cancer Centre
Address:
City:
Toronto
Zip:
M5G IZ5
Country:
Canada
Status:
Recruiting
Facility:
Name:
Institut Bergonie
Address:
City:
Bordeaux
Zip:
33076
Country:
France
Status:
Recruiting
Facility:
Name:
Centre Leon Berard
Address:
City:
Lyon
Zip:
69373
Country:
France
Status:
Recruiting
Facility:
Name:
Institut Paoli-Calmettes
Address:
City:
Marseille
Zip:
13009
Country:
France
Status:
Recruiting
Facility:
Name:
Centre Eugene Marquis
Address:
City:
Rennes
Zip:
35042
Country:
France
Status:
Recruiting
Facility:
Name:
Institut Gustave Roussy
Address:
City:
Villejuif
Zip:
94805
Country:
France
Status:
Recruiting
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori
Address:
City:
Milano
Zip:
20133
Country:
Italy
Status:
Recruiting
Facility:
Name:
Ospedale San Raffaele
Address:
City:
Milan
Zip:
20132
Country:
Italy
Status:
Recruiting
Facility:
Name:
Vall d'Hebron Institute of Oncology
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Clinic de Barcelona
Address:
City:
Barcelona
Zip:
08036
Country:
Spain
Status:
Recruiting
Facility:
Name:
START Madrid Fundacion Jimenez Diaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario La Paz
Address:
City:
Madrid
Zip:
28046
Country:
Spain
Status:
Recruiting
Facility:
Name:
Next Oncology - Hospital Quironsalud Madrid
Address:
City:
Pozuelo de Alarcon
Zip:
28223
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Marques de Valdecilla
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute UK
Address:
City:
London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Start date:
July 17, 2020
Completion date:
December 2026
Lead sponsor:
Agency:
BicycleTx Limited
Agency class:
Industry
Source:
BicycleTx Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT04561362
