This phase I/II trial tests the safety, side effects, and effectiveness of axatilimab in combination with retifanlimab and paclitaxel for the treatment of patients with a solid tumor that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). Axatilimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. Giving axatilimab in combination with retifanlimab and paclitaxel may be safe, tolerable and/or effective in treating patients with advanced or metastatic solid tumors.
Ability to comprehend the investigational nature of the study and provide informed consent. Written informed consent must be obtained prior to any study specific procedures or interventions
Age ≥ 18 years at the time of consent. All participants, irrespective of their gender, gender identity, race, and ethnicity, will be included
Certified, documented diagnosis of a metastatic solid tumor based on pathology review
Presence of at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and another lesion that is amenable to tumor biopsy
New or progressive brain metastases. Patients with brain metastases not requiring immediate central nervous system (CNS) specific treatment or stable for at least 4 weeks prior to study day -8 are eligible at the discretion of the investigator given that neurologic symptoms are resolved.
Patients with active leptomeningeal disease are not eligible
Palliative radiation therapy administered within 1 week prior to study day -8, Note: Participants must have recovered from all radiation-related toxicities (to grade < 1 or baseline), must not require corticosteroids for this purpose, and must not have had radiation pneumonitis
Immunization with a live vaccine within 28 days prior to study day -8
Single group
Axatilimab
Biological/VaccineGiven IV
Biopsy
Procedure/SurgeryUndergo tumor biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo CT scan
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Paclitaxel
DrugGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET scan
Retifanlimab
Biological/VaccineGiven IV
Incidence of dose limiting toxicities (phase Ib)
Will be coded by system organ class, MedDRA preferred term, and severity grade using Common Terminology Criteria for Adverse Events (version 5.0).
Recommended phase 2 dose of the study drug combination (phase Ib)
Clinical benefit rate (phase Ib/II)
Defined as percentage of participants with complete response or partial response confirmed by scans at least 4 weeks apart, or stable disease for \> 4 months. Will be reported with exact 95% confidence interval.
Incidence of ≥ grade 3 toxicities possibly or definitely related to study drugs
Will be categorized and tabulated for reporting. The analyses for reporting may include descriptive statistical analyses of the overall set of phase II adverse events.
Changes in immune cell composition and functionality
Will be characterized in peripheral blood using flow cytometry (FC) and candidate protein biomarkers will be identified in tumor tissue using multiplexed immunohistochemistry. Changes in immune cell composition and functionality at the biopsy during cycle 2 will be assessed by paired t-test.
Change in immune cell population
To assess predictive biomarkers of response in peripheral blood, changes in immune cell populations in peripheral blood, including reduced presence of CD14dimCD16+ monocytes and increased presence of CD8+ T effector memory subsets, at the end of the study between responders and non-responders will be assessed using repeated measures of analysis of covariance over time to accommodate a longitudinal nature of peripheral blood draws for flow cytometry.
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OHSU Knight Cancer Institute
Lead sponsor
Oregon Health and Science University
Collaborator
Incyte Corporation
Collaborator
