Trial Title:
AGEN1423 and Botensilimab w/ or w/o Chemo in PDAC
NCT ID:
NCT05632328
Condition:
Advanced Pancreatic Ductal Adenocarcinoma
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Paclitaxel
Gemcitabine
Antibodies, Bispecific
Conditions: Keywords:
Advanced Pancreatic Ductal Adenocarcinoma
Pancreatic Ductal Adenocarcinoma
Pancreatic Cancer
Chemotherapy
Immunotherapy
AGEN1423
Botensilimab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AGEN1423
Description:
via IV, dosage per protocol, once every 2 weeks for up to 8 weeks
Arm group label:
COHORT 1: AGEN1423 Plus Botensilimab
Arm group label:
COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy
Other name:
Anti-CD73-TGFβ-Trap Bifunctional Antibody
Intervention type:
Drug
Intervention name:
Botensilimab
Description:
via IV, dosage per protocol, once evert 2 weeks, up to 2 years
Arm group label:
COHORT 1: AGEN1423 Plus Botensilimab
Arm group label:
COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
per standard care
Arm group label:
COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy
Other name:
Gemzar
Intervention type:
Drug
Intervention name:
Nab-paclitaxel
Description:
per standard care
Arm group label:
COHORT 2: AGEN1423 Plus Botensilimab and Chemotherapy
Other name:
Abraxane
Summary:
The goal of this research study is to asses the safety and efficacy of the combination of
AGEN1423 and Botensilimab with or without chemotherapies, gemcitabine and nab-paclitaxel,
for the treatment of advanced pancreatic ductal adenocarcinoma (PDAC) which has
progressed after at least one previous line of cancer therapy.
The names of the study drugs involved in this study are:
- AGEN1423
- Botensilimab
Participants will receive study treatment for about 2 years and will be followed for 1
year after.
Detailed description:
The research study procedures include screening for eligibility and study treatment
including evaluations and follow up visits.
- Participants will receive study treatment for about 2 years and will be followed for
1 year. If the combination is considered to be safe and tolerable, and objective
response is achieved in at least 2 patients, the study will proceed to Cohort 2.
- This research study involves immunotherapy. The names of the study drugs involved in
this study are:
- AGEN1423
- Botensilimab
It is expected that about 24 people will take part in this part of this research
This research study is a Phase II clinical trial. Phase II clinical trials test the
safety and effectiveness of an investigational drug to learn whether the drug works in
treating a specific disease. "Investigational" means that the drug is being studied. The
U.S. Food and Drug Administration (FDA) has not approved AGEN1423 as a treatment for any
disease. The U.S. Food and Drug Administration (FDA) has not approved Botensilimab as a
treatment for any disease.
Agenus, a pharmaceutical company, is supporting this research study by providing funding
and study drug for the research study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 18 year and older
- Ability to understand and willingness to sign a written informed consent prior to
entering the study.
- Histologically or cytologically confirmed (either previously or newly biopsied)
metastatic or locally advanced unresectable pancreatic adenocarcinoma, including
intraductal papillary mucinous neoplasm.
- Have measurable disease (≥ 1 measurable lesion) based on RECIST v1.1 as determined
by the site study team. Tumor lesions situated in a previously irradiated area are
considered measurable if progression has been demonstrated in such lesions.
- Previous treatment lines
- Cohort 1: Have documented objective radiographic progression on or after
stopping treatment with first-line or further therapy, i.e. chemotherapy and or
radiotherapy. If subjects received prior neoadjuvant or adjuvant chemotherapy
and progressed within 3 months of the last dose, then this should be considered
as a prior line of systemic therapy.
- Cohort 2: Have documented objective radiographic progression on or after
stopping treatment with first-line, fluorouracil-based chemotherapy.
- For Cohort 1, willing to submit an evaluable fresh tumor tissue sample, unless tumor
is considered inaccessible, or biopsy is otherwise considered not in the subject's
best interest.
- Complete resolution of toxic effect(s) of the most recent prior chemotherapy to
Grade 1 or less (except alopecia and peripheral neuropathy). If the subject received
major surgery or radiation therapy of > 30 Gy, they must have recovered from the
toxicity and/or complications from the intervention.
- ECOG status ≤1
- Life expectancy of at least 3 months
- Participants must have adequate organ and marrow function as defined below. All
laboratory assessments should be performed within 10 days of treatment initiation
- Hematological:
- Hemoglobin ≥ 9g/dL (without transfusion within 7 days of assessment)
- Leukocytes ≥3,000/µL
- Absolute neutrophil count ≥1,500/µL
- Absolute lymphocyte count ≥700/µL
- Platelets ≥100,000/µL
- Hepatic Function
- Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN
- Renal Function
---Creatinine Clearance > 50 mL/min as calculated per Cockcroft-Gault formula
- Nutritional
---Serum Albumin ≥ 3 g/dL
- Coagulation
- INR or PT: ≤1.5xULN unless subject is receiving anticoagulant therapy as
long as PT or PTT is within therapeutic range of intended use of
anticoagulants.
- aPTT: ≤1.5xULN unless subject is receiving anticoagulant therapy as long
as PT or PTT is within therapeutic range of intended use of anticoagulants
- Subjects must use effective contraception:
- Female subjects must be of non-childbearing potential or, if of childbearing
potential, must agree to use a highly effective method of birth control
(Appendix B), during the study and for 6 months following the last dose of
study medication and must have a negative urine or serum pregnancy test within
72 hours prior to taking study medication. If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required. The
serum pregnancy test must be negative for the subject to be eligible.
Non-childbearing potential is defined as (by other than medical reasons):
---≥45 years of age and has not had menses for over 2 years
---Amenorrhoeic for > 2 years without a hysterectomy and oophorectomy
- Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral
tubal ligation at least 6 weeks prior to Screening. Information must be
captured appropriately within the medical records.
- Male subjects must agree to use an adequate method of contraception starting
with the first dose of study therapy through 120 days after the last dose of
study therapy.
Exclusion Criteria:
- Has a pancreatic tumor other than adenocarcinoma, including: adenosquamous, acinar
cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine
neoplasms, squamous cell carcinoma, Vater and periampullary duodenal or common bile
duct malignancies.
- Subjects with a bowel obstruction.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has an active infection requiring systemic therapy or has an uncontrolled infection.
- Has an underlying medical condition that would preclude study participation.
- Has a disease that is suitable for therapy administered with curative intent.
- Is currently participating and receiving study therapy or has participated in a
study of an investigational agent and received study therapy or used an
investigational device within 4 weeks of the first dose of treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of
trial treatment
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from AE due to
agents administered more than 4 weeks earlier.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at
Baseline) from AE due to a previously administered agent (Subjects with ≤ Grade 2
neuropathy or ≤ Grade 2 alopecia are an exception to this criterion and may qualify
for the study. If subject underwent major surgery, they must have recovered
adequately from the toxicity and/or complications from the intervention prior to
starting therapy)
- An active autoimmune disease that has required systemic treatment in the 2 years
preceding the study (i.e., with the use of disease-modifying agents, corticosteroids
or immuno-suppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin,
or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
- Has a history of interstitial lung disease.
- O2 saturation < 92% (on room air).
- Has unstable angina, new onset angina within the last 3 months, myocardial
infarction within the last 6 months, and current congestive heart failure New York
Heart Association Class III or higher. For Cohort 2: has ventricular arrhythmias,
hypertensive urgency, or severe arterial thromboembolic events less than 6 months
prior to study initiation.
- Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating Investigator.
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial, starting with the Screening visit through 120 days
after the last dose of trial treatment. Women with a positive pregnancy test within
72 hours from Baseline.
- Has a positive Human immunodeficiency virus (HIV) positive test. Participants with
HIV positive test on effective anti-retroviral therapy with undetectable viral load
within 6 months are eligible for this trial.
- Has known history of Chronic Hepatitis B or C. For participants with evidence of
chronic hepatitis B virus (HBV) infection, if the HBV viral load is undetectable
while on suppressive therapy the subject can participate on the study. Participants
with a history of hepatitis C virus (HCV) infection must have been treated and
cured. For participants with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load.
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Note: Subjects with previously treated brain metastases may participate
provided they are stable (without evidence of progression by imaging using the
identical imaging modality for each assessment, either MRI or computerized
tomography (CT) scan, for at least four weeks prior to the first dose of trial
treatment and any neurologic symptoms have returned to baseline), have no evidence
of new or enlarging brain metastases, and are not using steroids for at least 14
days prior to trial treatment. This exception does not include carcinomatous
meningitis which is excluded regardless of clinical stability.
- Has received a live vaccine within 30 days of the planned start of study therapy.
Seasonal flu vaccines or COVID-19 vaccines that do not contain live virus are
permitted.
- Drainage of ascitic or pleural fluid 2 or more times in the 4 weeks prior to the
first dose of study drug or permanent drain in place (eg, PleurX®) for ascites or
pleural effusion symptom management.
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition of AGEN1423 or Botensilimab.
- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical cancer.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Beth Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bruno Bockorny, MD
Phone:
617-667-2100
Email:
bbockorn@bidmc.harvard.edu
Investigator:
Last name:
Bruno Bockorny, MD
Email:
Principal Investigator
Start date:
August 8, 2024
Completion date:
May 1, 2027
Lead sponsor:
Agency:
Bruno Bockorny
Agency class:
Other
Collaborator:
Agency:
Agenus Inc.
Agency class:
Industry
Collaborator:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Source:
Beth Israel Deaconess Medical Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05632328
