Trial Title:
BXCL701 and Pembrolizumab in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT05558982
Condition:
Metastatic Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Pembrolizumab
Conditions: Keywords:
Metastatic Pancreatic Ductal Adenocarcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BXCL701
Description:
BXCL701 0.3 mg, orally, twice a day on days 1-14 every 21 days
Arm group label:
BXCL701 plus Pembrolizumab
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Pembrolizumab 200 mg intravenous (IV) on day 1 every 21 days.
Arm group label:
BXCL701 plus Pembrolizumab
Other name:
Keytruda
Summary:
Single-arm, open label study to determine the 18 week progression-free survival rate of
the combination of BXCL701 and pembrolizumab in patients with pancreatic ductal
adenocarcinoma in the second-line metastatic setting.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically-confirmed pancreatic ductal adenocarcinoma with metastatic disease
(mixed histology is acceptable as long adenocarcinoma is the dominant histological
subtype)
- Patient must consent to two mandatory biopsies and have tumor amenable to serial
core biopsies
- Measurable disease by iRECIST v. 1.1 criteria (tumor ≥ 1 cm in longest diameter on
axial image on CT or MRI and/or lymph node(s) ≥ 1.5 cm in short axis on CT or MRI)
on baseline imaging
- Documented progression of disease or intolerance on at least one regimen for
metastatic disease (progression during or within 3 months of the completion of
adjuvant therapy is acceptable)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (see Table
2)
- Age ≥ 18 years
- Subjects with no brain metastases or a history of previously treated brain
metastases who have been treated by surgery or stereotactic radiosurgery (SRS) at
least 4 weeks prior to enrollment and have a baseline MRI that shows no evidence of
active intracranial disease
- Patients with available standard 12-lead ECG with the following parameters at
screening (defined as the mean of the triplicate ECGs):
o QTcB (Bazett's formula) interval at screening <480msec
- Bone marrow function: absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥100 ×
109/L; hemoglobin ≥ 8.0 g/dL (with no prior red blood cell transfusions during the
prior 14 days)
- Renal function: serum creatinine ≤ 1.5 × upper normal limit of institution's normal
range or creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine
levels above institutional normal
- Hepatic function: AST and ALT ≤ 3.0 × the upper normal limit of institution's normal
range. Total bilirubin ≤ 1.5 × the upper normal limit of institution's normal range.
For subjects with liver metastases, AST and ALT < 5 × the upper normal limit of
institution's normal range, and total bilirubin >1.5 - 3.0 x the upper normal limit
of institution's normal range are acceptable as long as there is no persistent
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or
eosinophilia.
- Patients must have fully recovered from all effects of surgery. Patients must have
had at least two weeks after minor surgery and four weeks after major surgery before
starting therapy. Minor procedures requiring "Twilight" sedation such as endoscopies
or mediport placement may only require a 24-hour waiting period, but this must be
discussed with an investigator.
- Women of childbearing potential must have a negative serum pregnancy test during the
screening period and on C1D1 and/or postmenopausal women must be amenorrheic for at
least 12 months to be considered of non-childbearing potential
- Patient is capable of swallowing pills whole.
- Patient is capable of understanding and complying with parameters as outlined in the
protocol and able to sign and date the informed consent, approved by the
Institutional Review Board (IRB), prior to the initiation of any screening or
study-specific procedures.
- Patient's acute toxic effects of previous anticancer therapy have resolved to ≤
Grade 1 except for Grade 2-3 peripheral neuropathy or any grade of alopecia.
- Male patients and their female partners of childbearing potential must agree and
commit to use a barrier contraception (e.g., condom with spermicidal
foam/gel/film/cream/ suppository) throughout the duration of the study until at
least 6 months following the last dose of study drug, in addition to their female
partners using either an intrauterine device or hormonal contraception and
continuing until at least 6 months following the last dose of study drug. This
criterion may be waived for male patients who have had a vasectomy >6 months before
signing the informed consent form.
Exclusion Criteria:
- Patients previously exposed to FAP inhibitors, DPP inhibitors, or monoclonal
antibodies targeting anti-PD-1, anti-PD-L1, or anti-CTLA-4.
- Prior anti-tumor therapy within 2 weeks of C1D1 (defined as, but not limited to,
anti-cancer agents (cytotoxic chemotherapy, immunotherapy, and biologic therapy),
radiotherapy, and investigational agents), the "washout period."
- Patient has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, cause unacceptable safety risks,
contraindicate patient participation in the clinical study or compromise compliance
with the protocol (e.g. chronic symptomatic pancreatitis, chronic active hepatitis,
active untreated or uncontrolled fungal, bacterial, or viral infection).
- Women who are pregnant or breastfeeding.
- Psychiatric illness or social situation that would limit compliance with study
requirements.
- Concurrent malignancy or malignancy within 2 years prior to C1D1, with the exception
of adequately treated cutaneous basal or squamous cell carcinoma, non-melanomatous
skin cancer, curatively resected cervical cancer, or any locally treated malignancy
deemed low likelihood for recurrence or metastasis by the investigator.
- Patients with central nervous system (CNS) involvement unless they meet ALL of the
following criteria:
- At least 4 weeks from prior therapy completion (including radiation and/or
surgery) to starting the study treatment
- Clinically stable CNS tumor at the time of screening and not receiving steroids
and/or enzyme-inducing anti-epileptic medications for brain metastases.
- Patient has impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
resection).
- Patient has a known history of HIV infection or chronic, active hepatitis B or C
(testing is not mandatory) - patients with hepatitis C status-post treatment with
undetectable viral load are eligible.
- Patient has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, cause unacceptable safety risks,
contraindicate patient participation in the clinical study or compromise compliance
with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active
untreated or uncontrolled fungal, bacterial or viral infections, etc.).
- Patient has uncontrolled, clinically significant pulmonary disease (e.g. chronic
obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the
investigator would put the patient at significant risk for pulmonary complications
during the study.
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormalities, including any of the following:
- History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to screening
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO) at screening
- Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia),
complete left bundle branch block, high-grade AV block (e.g. bifascicular
block, Mobitz type II and third-degree AV block)
- Long QT syndrome or family history of idiopathic sudden death or congenital
long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia.
- Concomitant use of medication(s) with a known risk to prolong the QT interval
and/or known to cause Torsades de Pointe that cannot be discontinued (within 5
half-lives or 7 days prior to starting study drug) or replaced by safe
alternative medication
- Inability to determine the QT interval on screening
- Patients with history of symptomatic orthostatic hypotension within 3 months prior
to enrollment, defined as a drop in systolic blood pressure (SBP) of ≥ 20 mmHg or
diastolic blood pressure (DBP) of ≥ 10 mmHg with assumption of an upright posture.
- Patients with a history of (non-infectious) pneumonitis that required steroids,
current pneumonitis, or those who have a history of interstitial lung disease.
- Patients who have received a live-virus vaccination within 30 days of planned
treatment start date.
- Patient must not have active known or suspected autoimmune disease requiring
systemic treatment in the past 2 years (i.e., with use of disease modifying agents,
corticosteroids, or immunosuppressive drugs). Subjects with type I diabetes
mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as
vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions
not expected to recur in the absence of an external trigger (e.g., celiac disease)
are permitted to enroll.
- Patient must not have a condition requiring systemic treatment with either
corticosteroids or other immunosuppressive medications within 14 days of
randomization. Inhaled or topical steroids, and adrenal replacement steroid doses
≤10 mg daily prednisone equivalents are permitted in the absence of active
autoimmune disease.
- Prisoners.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Georgetown Lombardi Comprehensive Cancer Center
Address:
City:
Washington
Zip:
20007
Country:
United States
Status:
Recruiting
Contact:
Last name:
Princess Jones
Phone:
202-687-3091
Email:
paj24@georgetown.edu
Investigator:
Last name:
Benjamin Weinberg, MD
Email:
Principal Investigator
Facility:
Name:
Medstar Washington Hospital Center
Address:
City:
Washington
Zip:
20010
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Anteneh Tesfaye, MD
Email:
Principal Investigator
Facility:
Name:
John Theurer Cancer Center at Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Suzanne Kosky
Phone:
551-996-3986
Email:
suzanne.kosky@hmhn.org
Investigator:
Last name:
Martin Gutierrez, MD
Email:
Principal Investigator
Start date:
August 16, 2023
Completion date:
November 2027
Lead sponsor:
Agency:
Georgetown University
Agency class:
Other
Collaborator:
Agency:
BioXcel Therapeutics Inc
Agency class:
Industry
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Georgetown University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05558982
