RiLEY: 9-ING-41 Plus Retifanlimab and Gemcitabine/Nab-Paclitaxel in Patients With Advanced Pancreatic Adenocarcinoma
Study Details
Study Description
Brief Summary
To determine the rate of disease control of the combination of 9-ING-41 and retifanlimab plus gemcitabine/nab-paclitaxel in patients with pancreatic cancer without prior systemic therapy for advanced disease.
The researchers will be looking at how the cancer you have reacts to the addition of 9-ING-41 and retifanlimab to the standard of care chemotherapy treatment. They want to discover if using this combination will help and is able to keep the cancer you have from progressing.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 9-ING-41 plus Retifanlimab plus Gem/Abraxane intravenous (IV) infusion of nab-paclitaxel at a dose of 125 mg per square meter, followed by an infusion of gemcitabine according to the gemcitabine label at a dose of 1000 mg per square meter, on days 1, 8, 15 of a 28-day cycle. Retifanlimab 500 mg IV on day 1 of a 28-day cycle. (Retifanlimab will be administered following gemcitabine/nab-paclitaxel.) 9-ING-41 administered at a dose of 9.3 mg/kg by IV infusion twice weekly on Days 1 and 4 of each week of a 28-day cycle. (9-ING-41 will be administered following retifanlimab.) |
Drug: 9-ING-41
9-ING-41 is a small molecule potent selective GSK-3β inhibitor
Drug: Retifanlimab
Humanized, hinge-stabilized, IgG4κ monoclonal antibody that recognizes human PD-1.
Other Names:
Drug: Gemcitabine
cytotoxic chemotherapy agent
Drug: Abraxane
cytotoxic chemotherapy agent
|
Outcome Measures
Primary Outcome Measures
- Disease Control Rate [From date of enrollment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months]
Secondary Outcome Measures
- Overall Response Rate (ORR) [From date of enrollment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months]
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [From date of enrollment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 60 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Is able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures.
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Is aged ≥ 18 years.
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Has pathologically confirmed advanced, recurrent, or metastatic pancreatic cancer AND is previously untreated with systemic agents in the advanced/metastatic setting.
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Must have at least 1 measurable lesion per RECIST v1.1. Lesions that are radiated should not count as target lesions unless there is evidence of growth post radiation on a subsequent scan prior to trial enrollment.
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Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1000/mL; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100,000/mL.
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Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x ULN (≤ 5 X the upper limit of normal (ULN) in the setting of liver metastasis or infiltration with malignant cells); bilirubin ≤ 1.5 x ULN.
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Adequate renal function: creatinine clearance CrCl > 60 mL/min measured or calculated by Cockcroft- Gault (C-G) equation (estimated glomerular filtration rate [eGFR] can also be used in place of CrCl).
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Serum amylase and lipase ≤ 1.5 x ULN
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Eastern Co-operative Oncology Group (ECOG) performance status (PS) 0 - 1
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Has received the final dose of any of the following treatments/ procedures within the specified minimum intervals before first dose of study drug: Focal radiation therapy - 7 days Surgery with general anesthesia - 7 days Surgery with local anesthesia - 7 days
Exclusion Criteria:
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Is pregnant or lactating.
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Is known to be hypersensitive to any of the components or metabolites of 9-ING-41 or to the excipients used in its formulation, or known sensitivity to one of the chemotherapeutic agents or to the PD-1 inhibitor.
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History of receiving prior treatment with any anti-PD-1, PD-L1 or PD-L2 agent.
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Has endocrine or acinar pancreatic carcinoma.
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Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia, anemia not requiring transfusion support and infertility. Recovery is defined as ≤ Grade 1 or baseline severity per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5.0).
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Has significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, or stroke within 6 months of the first dose of 9-ING-41, or cardiac arrhythmia requiring medical treatment detected at screening.
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Has had a myocardial infarction within 12 weeks of the first dose of 9-ING-41 or has electrocardiogram (ECG) abnormalities that are deemed medically relevant by the investigator or study medical coordinator.
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Has symptomatic rapidly progressive brain metastases or leptomeningeal involvement as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). Patients with stable brain metastases or leptomeningeal disease or slowly progressive disease are eligible provided that they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug.
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Has had major surgery (not including placement of central lines) within 7 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered).
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Has any medical and/or social condition that, in the opinion of the investigator would preclude study participation.
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Has received an investigational anti-cancer drug in the 14-day period before the first dose of study drug (or within 5 half-lives if longer) or is currently participating in another interventional clinical trial.
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Has a current malignancy other than pancreatic cancer.
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Known immunodeficiency syndrome or active autoimmune disease or requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg/day of prednisone or equivalent).
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Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
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Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy that is > 30 Gy within 6 months of the first dose of study treatment.
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Has received systemic antibiotics ≤ 7 days prior to the first dose of study drug.
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History of organ transplant, including allogeneic stem cell transplantation.
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Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids).
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Known allergy or hypersensitivity to any component of retifanlimab or formulation components.
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Has received a live vaccine within 28 days of the planned start of study drug.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kansas University Cancer center | Fairway | Kansas | United States | 66205 |
Sponsors and Collaborators
- University of Kansas Medical Center
- Actuate Therapeutics Inc.
- Incyte Corporation
Investigators
- Principal Investigator: Anwaar Saeed, MD, Kansas University Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IIT-2021-RiLEY