Status and phase
Conditions
Treatments
About
This study is being done to test the safety and effectiveness of combining domvanalimab (AB154), zimberelimab (AB122), and APX005M with pancreatic cancer that has spread to other parts of body.
This research study involves immunotherapy. Immunotherapy triggers the body's immune system to fight cancer cells.
The names of the study drugs involved in this study are:
Full description
This is an open-label, Phase 1b/2, multicenter, randomized study evaluating the safety and efficacy of 'switch maintenance' combination immunotherapy (domvanalimab) zimberelimab and APX005M versus 'continuous maintenance' in patients with metastatic pancreatic cancer following 4-6 months of FOLFIRINOX
The names of the study drugs involved in this study are:
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
Participants will be randomized into one of two groups:
If you are in Arm B and the drugs stop working, participants may receive the drugs given in Arm A.
Participants will receive study treatment as long the disease does not worsen or there are no serious side effects for a maximum of 26 cycles (2 years) and will be followed for 12 months after the discontinue the study drugs.
It is expected that about 46 people will take part in this research study.
This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an investigational drug or drugs and also tries to define the appropriate dose of the investigational drug(s) to use for further studies. Phase II clinical trials test the safety and effectiveness of an investigational drug or drugs 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 domvanalimab, zimberelimab, or APX005M as a treatment for any disease.
drug regimen.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion Criteria:
Participants must have histologically confirmed pancreatic cancer (adenocarcinoma, squamous, or adenosquamous histologies) that is metastatic and for which standard curative or palliative measures do not exist or are no longer effective. Locally advanced patients are not eligible.
Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.
Participants must have received 8-12 cycles (4-6 months) of first-line FOLFIRINOX or modified FOLFIRINOX with stable disease or better.
Age ≥18 years. Because no dosing or adverse event data are currently available on the use of domvanalimab + zimberelimab + APX005M in participants <18 years of age, children are excluded from this study.
ECOG performance status ≤1
Participants must have adequate organ and marrow function as defined below:
Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. If a participant has brain or meningeal metastases, the participant must meet the following criteria:
Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
Participants must be willing to undergo a pre-treatment fresh tumor biopsy.
Participants must be willing to undergo an on-treatment tumor biopsy (if medically feasible).
Participants must have archival tissue available for analysis, which will be used for correlative studies if a pretreatment biopsy reveals necrotic tissue.
Ability to understand and the willingness to sign a written informed consent document.
Willing and able to comply with the requirements and restrictions in this protocol.
Eligibility Criteria for Stage 2 (Crossover Stage)
Availability of a tumor specimen from on-treatment biopsy during Expansion Phase. If this is not available, willingness to undergo biopsy prior to initiation of Crossover Phase.
Exclusion Criteria (for both Stage 1 and Stage 2)
Patients who have evidence of disease progression on FOLFIRINOX.
Participants who have had cytotoxic chemotherapy, radiotherapy, within 2 weeks prior to the first dose of study medication or those who have not recovered to ≤ CTCAE Grade 1 or baseline from adverse events due to agents administered more than 2 weeks earlier. Exceptions include alopecia of any grade and Grade ≤ 2 peripheral neuropathy.
Participants who have received any other investigational agents for pancreatic cancer.
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, or allergic reactions attributed to compounds of similar chemical or biologic composition to domvanalimab, zimberelimab, APX005M, or other agents used in study.
Prior treatment with any of the protocol-specified study treatments, with the exception of chemotherapy.
Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies (including anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-TIGIT, and CD40 agonist therapeutic antibodies)
Patients with endocrine or acinar pancreatic carcinoma are not eligible for the study.
Known dihydropyrimidine dehydrogenase deficiency.
Known germline BRCA1 or BRCA2 mutation(s).
Participants who have undergone major surgery 28 days prior to initiating protocol therapy. Participants must have sufficiently recovered from adverse events caused by the procedure as judged by the treating investigator. Placement of central venous access catheter (e.g., port or similar) is not considered a major surgical procedure.
Participants must not have a history of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV), except for the following:
Participants must not have a history of primary immunodeficiency.
Active autoimmune disease, history of autoimmune disease, or concurrent administration of immune suppressive medications. Participants must not have a known or suspected history of an autoimmune disorder within 3 years of the first dose of investigational agent, including but not limited to: systemic lupus erythematosus, scleroderma, inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, sarcoidosis, or autoimmune hepatitis. Exceptions include participants with Type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement, skin disorders such as alopecia or vitiligo, not requiring systemic therapy, resolved childhood asthma/atopy, or conditions not expected to recur in the absence of an external trigger are eligible. Patients with a history of Hashimoto syndrome within 3 years of the first dose of investigational agent, which resolved to hypothyroidism alone.
Prior allogeneic bone marrow transplantation or solid organ transplantation.
Participants must not receive concurrent or prior use of an immunosuppressive agent within 14 days prior to the first dose of investigational agent. Exceptions include:
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
Patients must not have received a live attenuated vaccine within 28 days before the first dose of investigational agent, and patients, if enrolled, should not receive live vaccines during the study or for 180 days after the last dose of investigational agent. Prior COVID-19 infection and/or COVID-19 vaccination is permitted.
Known hereditary or acquired coagulopathy (e.g., hemophilia, von Willebrand disease, cancer-associated diffuse intravascular coagulation)
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of the initiation of investigational therapy), clinically significant cardiovascular disease, unstable angina pectoris, cardiac arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or psychiatric illness/social situations that would limit compliance with study requirements.
Participants with a history of a clinically relevant second primary malignancy within the past 2 years. Exceptions include: resected basal and squamous cell carcinomas of the skin and completely resected carcinoma in situ of any type.
Primary purpose
Allocation
Interventional model
Masking
46 participants in 4 patient groups
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Central trial contact
James Cleary, MD, PhD
Data sourced from clinicaltrials.gov
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