Trial Title:
Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression
NCT ID:
NCT04180371
Condition:
Advanced Solid Tumor Historically Known for High EphA2 Expression
Urothelial Cancer
Ovarian Cancer
Non-small Cell Lung Cancer
Head and Neck Cancer
Triple Negative Breast Cancer
Gastric/Upper Gastrointestinal Cancer
Conditions: Official terms:
Ovarian Neoplasms
Triple Negative Breast Neoplasms
Gastrointestinal Neoplasms
Nivolumab
Conditions: Keywords:
EphA2
ovarian cancer
urothelial cancer
bladder cancer
NSCLC
TNBC
gastric cancer
GEJ cancer
HNSCC
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:
BT5528
Description:
Participants will receive a 60-minute intravenous infusion of BT5528 once a week (Days 1,
8, 15, and 22) or every other week (Days 1 and 15) on a 4-week cycle at the selected
dose.
Arm group label:
Phase I - Dose escalation (BT5528)
Arm group label:
Phase I - Dose escalation combination (BT5528 & nivolumab)
Arm group label:
Phase II - Dose expansion 1 (BT5528)
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Participants will receive nivolumab at 480mg intravenous infusion every 4 weeks.
Arm group label:
Phase I - Dose escalation combination (BT5528 & nivolumab)
Other name:
Opdivo
Summary:
This clinical trial is evaluating a drug called BT5528 alone and in combination with
nivolumab in participants with advanced solid tumors historically known for expression of
EphA2. The main goals of this study are to:
- Find the recommended dose(s) of BT5528 that can be given safely to participants
alone and in combination with nivolumab
- Learn more about the side effects of BT5528
- Learn about how effective BT5528 is for the treatment of ovarian cancer,
urothelial/bladder cancer, lung cancer (NSCLC), triple-negative breast cancer, head
and neck cancer (HNSCC), and gastric/upper gastrointestinal cancer.
- Learn more about BT5528 therapy alone and in combination with nivolumab.
Detailed description:
BT5528 consists of a bicyclic peptide (Bicycle®) which binds to EphA2, and is covalently
attached to a spacer and a protease cleavable peptide linker attached to MMAE.
The Phase I/II multi-center, open-label trial will evaluate BT5528 administered
once-weekly as a single agent and in combination with nivolumab. The Phase I portion is a
dose escalation primarily designed to assess the safety and tolerability of BT5528 and to
determine recommended Phase II dose(s) (RP2D). Following selection of a recommended Phase
II dose(s) (RP2D), a dose expansion portion will be initiated with the primary objective
of evaluating the clinical activity of BT5528.
Criteria for eligibility:
Criteria:
General Inclusion:
- Written informed consent, according to local guidelines, signed and dated by the
patient or by a legal guardian prior to the performance of any study-specific
procedures, sampling or analyses
- At least 18 years-of-age at the time of signature of the informed consent form
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Acceptable renal, hepatic, hematologic and coagulation functions
- Negative pregnancy test for women of childbearing potential
- Male participants with female partners of childbearing potential and female
participants of childbearing potential are required to follow highly effective
contraception
- All patients must have tumor tissue (fresh or archived) available for analysis of
EphA2 tumor expression and other biomarkers. In the absence of available tumor
tissue, patients must be willing to undergo a biopsy to provide fresh tumor samples
- Life expectancy ≥12 weeks after the start of BT5528 treatment according to the
Investigator's judgment.
- Must be willing and able to comply with the protocol and study procedures.
Additional inclusion criteria for Phase I (dose escalation phase, with BT5528 alone or in
combination with nivolumab):
- Metastatic recurrent histologically confirmed malignant solid tumors historically
known for high EphA2 tumor expression. Confirmation of EphA2 expression prior to
enrollment is not required for participants with ovarian cancer and specific other
individual tumor types.
- Exhausted all appropriate treatment options per local guidelines
Additional inclusion criteria for Phase II (dose expansion phase, with BT5528 alone):
- Participants with metastatic recurrent disease histologically confirmed to be
non-small cell lung cancer, ovarian cancer, triple-negative breast cancer (TNBC),
gastric/upper gastrointestinal (GI) cancer, head and neck (H&N) cancer, urothelial
cancer are eligible and must have failed or are ineligible for all appropriate
treatment options per local guidelines and must have evidence of radiographic
progression on the most recent line of therapy
- Patients with urothelial cancer who have previously received treatment with
enfortumab vedotin (EV) are eligible to the study. Patients who received EV and
showed disease progression within 6 months of treatment start are planned for less
than 50% of total patients enrolled in the cohort
Exclusion criteria (all participants):
- Chemotherapy treatments within 14 days prior to first dose of study treatment, other
anticancer treatments, treatment within 28 days or 5 half-lives, whichever is the
shorter
- Experimental treatments within 4 weeks of first dose of BT5528
- Prior toxicities must have resolved to Grade 1 per Common Terminology Criteria for
Adverse Events (CTCAE) v 5.0 (except alopecia which can be Grade 2)
- Current treatment with strong inhibitors or inducers of CYP3A4 or strong inhibitors
of P-gp
- Known sensitivity to any of the ingredients of the investigational product or
monomethyl auristatin E (MMAE)
- Any condition, therapy or laboratory abnormality that might confound the results of
the study, interfere with the patient's participation, or is not in the best
interest of the patient to participate in the opinion of the investigator including
but not limited to specific cardiovascular criteria
- Major surgery (excluding placement of vascular access) within 4 weeks of first dose
of BT5528 study treatment and must have recovered adequately prior to starting study
therapy
- Receipt of live vaccine within 30 days of study treatment
- Untreated CNS metastases or leptomeningeal disease
- Uncontrolled hypertension (systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg that is
not responsive to intervention) at screening or prior to initiation of study drug.
- History or current evidence of any condition, therapy or laboratory abnormality that
might confound the results of the study, interfere with the patient's participation,
or is not in the best interest of the patient to participate in the opinion of the
Investigator including but not limited to:
(a) Patients with history of a cerebral vascular event (stroke or transient ischemic
attack), unstable angina, myocardial infarction, congestive heart failure or
symptoms of New York Heart Association Class III-IV documented within 6 months prior
to first dose of BT5528 or: (i) Mean resting corrected QT interval (QTcF) >470 msec
(ii) Any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalemia, congenital long QT syndrome, family
history of long QT syndrome or unexplained sudden death under 40 years-of-age, or
any concomitant medication known to prolong the QT interval (iii) Any clinically
important abnormalities (as assessed by the Investigator) in rhythm, conduction, or
morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch
block, third degree heart block
- Known human immunodeficiency virus (HIV) or acquired immune deficiency syndrome
(AIDS). Note: Well controlled HIV will be allowed if the patient meets all the
following criteria at inclusion:
1. CD4+ T-cell (CD4+) counts ≥350 cells/uL;
2. HIV viral load <400 copies/mL
3. Without a history of opportunistic infection within the last 12 months.
4. On established antiretroviral therapy (ART) for at least 4 weeks. Use of
anti-retroviral therapy is permitted, but should be discussed with the Medical
Monitor on a case-by-case basis.
- Patients with a positive hepatitis B surface antigen and/or anti-hepatitis B core
antibody. Patients with a negative polymerase chain reaction (PCR) assay are
permitted with appropriate antiviral therapy
- Active hepatitis C infection with positive viral load if hepatitis C virus (HCV)
antibody positive (if antibody is negative then viral load not applicable). Patients
who have been treated for hepatitis C infection can be included if they have
documented sustained virologic response of ≥12 weeks.
- Thromboembolic events and/or bleeding disorders 3 months (e.g., deep vein thrombosis
[DVT] or pulmonary embolism [PE]) prior to first dose
- Prior history of pneumonitis with presence of residual symptoms
- History of another malignancy within 3 years before the first dose of BT5528, or any
evidence of residual disease from a previously diagnosed malignancy (excluding
adequately treated with curative intent basal cell carcinoma, squamous cell of the
skin, cervical intraepithelial neoplasia/cervical carcinoma in situ or melanoma in
situ or ductal carcinoma in situ of the breast).
- Systemic anti-infective treatment or fever within the last 14 days prior to first
dose of BT5528 study treatment
- Psychological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol and/or follow-up procedures outlined in the protocol.
Additional Exclusion Criteria (BT5528 in combination with nivolumab):
- Prior intolerance to immune checkpoint inhibitor
- Known hypersensitivity to checkpoint inhibitor therapy
- Prior organ transplant (including allogeneic)
- Diagnosis of clinically relevant immunodeficiency
- Active systemic infection requiring therapy
- More than 10 mg daily prednisone equivalent or other strong immunosuppressant
- History of autoimmune disease except alopecia or vitiligo
- History of interstitial lung disease
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
California Cancer Associates for Research and Excellence, Inc.
Address:
City:
Encinitas
Zip:
92024
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Alberto Bessudo, MD
Email:
Principal Investigator
Facility:
Name:
University of California, San Diego (UCSD) - Medical Center
Address:
City:
La Jolla
Zip:
92037
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Shumei Kato, MD
Email:
Principal Investigator
Facility:
Name:
University of California - Irvine Medical Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Misako Nagasaka, MD
Email:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute at HealthONE
Address:
City:
Denver
Zip:
80218
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Gerald Falchook, MD, MS
Email:
Principal Investigator
Facility:
Name:
Florida Cancer Specialists
Address:
City:
Sarasota
Zip:
34232
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Judy Wang, MD
Email:
Principal Investigator
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Withdrawn
Facility:
Name:
Barbara Ann Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Hirva Mamdani, MD
Email:
Principal Investigator
Facility:
Name:
Comprehensive Cancer Centers of Nevada
Address:
City:
Las Vegas
Zip:
89169
Country:
United States
Status:
Completed
Facility:
Name:
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10021
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Min-Yuen Teo, MD
Email:
Principal Investigator
Facility:
Name:
Stephenson Cancer Center (Oklahoma University)
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Raid Aljumaily, MD
Email:
Principal Investigator
Facility:
Name:
Sidney Kimmel Cancer Center at Thomas Jefferson University
Address:
City:
Philadelphia
Zip:
19107
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Babar Bashir, MD
Email:
Principal Investigator
Facility:
Name:
Women and Infants Hospital
Address:
City:
Providence
Zip:
02905
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Matthews Cara, MD
Email:
Principal Investigator
Facility:
Name:
Tennessee Oncology, PLLC
Address:
City:
Nashville
Zip:
37221
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Meredith McKean, MD, MPH
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Jordi Rodon Ahnert, MD
Email:
Principal Investigator
Facility:
Name:
Virginia Cancer Specialists
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Alexander Spira, MD
Email:
Principal Investigator
Facility:
Name:
Froedtert Hospital and the Medical College of Wisconsin
Address:
City:
Milwaukee
Zip:
53226
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Jonathan Thompson, MD
Email:
Principal Investigator
Facility:
Name:
Institut Jules Bordet
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Status:
Recruiting
Investigator:
Last name:
Dr. Nuria Kotecki
Email:
Principal Investigator
Facility:
Name:
Cliniques Universitaires Saint-Luc
Address:
City:
Bruxelles
Country:
Belgium
Status:
Recruiting
Investigator:
Last name:
Jean-Pascal Machiels, MD,PhD
Email:
Principal Investigator
Facility:
Name:
Antwerp University Hospital (UZA)
Address:
City:
Edegem
Country:
Belgium
Status:
Recruiting
Investigator:
Last name:
Hans Prenen, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Universitair Ziekenhuis Gent (UZ)
Address:
City:
Gent
Zip:
9000
Country:
Belgium
Status:
Recruiting
Investigator:
Last name:
Dr. Sylvie Rottey
Email:
Principal Investigator
Facility:
Name:
Gachon University Gil Medical Center
Address:
City:
Incheon
Zip:
21565
Country:
Korea, Republic of
Status:
Completed
Facility:
Name:
Severance Hospital, Yonsei University Health System
Address:
City:
Seoul
Zip:
3722
Country:
Korea, Republic of
Status:
Completed
Facility:
Name:
Institut Catala d'Oncologia - L'Hospitalet
Address:
City:
Barcelona
Zip:
08908
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Juan Martin Liberal
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario Vall d'Hebron
Address:
City:
Barcelona
Zip:
8035
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Elena Garralda Cabanas, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Fundación Jimenez Diaz
Address:
City:
Madrid
Zip:
28040
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Bernard Doger de Speville, MD
Email:
Principal Investigator
Facility:
Name:
Hospital Universitario 12 de Octubre
Address:
City:
Madrid
Zip:
28041
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Luis Paz-Ares Rodriguez, MD
Email:
Principal Investigator
Facility:
Name:
Centro Integral Oncologico Clara Campal
Address:
City:
Madrid
Zip:
28050
Country:
Spain
Status:
Recruiting
Investigator:
Last name:
Emiliano Calvo Aller, MD
Email:
Principal Investigator
Facility:
Name:
Cambridge University Hospitals NHS Foundation Trust
Address:
City:
Cambridge
Zip:
CB2 0QQ
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Bristi Basu, MD
Email:
Principal Investigator
Facility:
Name:
The Leeds Teaching Hospitals NHS Trust Of Trust Headquarters, St James's University Hospital
Address:
City:
Leeds
Zip:
LS9 7TF
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Fiona Collinson, MD
Email:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute UK
Address:
City:
London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Elisa Fontana, MD
Email:
Principal Investigator
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Louise Carter, MBBS, PhD
Email:
Principal Investigator
Facility:
Name:
Sir Bobby Robson Cancer Trials Research Centre, The Northern Center for Cancer Care, Freeman Hospital
Address:
City:
Newcastle Upon Tyne
Zip:
NE7 7DN
Country:
United Kingdom
Status:
Recruiting
Investigator:
Last name:
Dr. Alistair Greystoke
Email:
Principal Investigator
Start date:
November 7, 2019
Completion date:
October 1, 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/NCT04180371
