A Phase Ib/II Study of Axatilimab in Combination With Retifanlimab and Paclitaxel for the Treatment of Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- Axatilimab
- Conditions
- Advanced Malignant Solid Neoplasm
- Sponsor
- OHSU Knight Cancer Institute
- Enrollment
- 38
- Locations
- 1
- Primary Endpoint
- Incidence of dose limiting toxicities (phase Ib)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVES: I. Phase Ib: Determine the safety and tolerability of the combination of axatilimab, retifanlimab, and paclitaxel in patients with advanced solid tumors. II. Phase II: Determine the efficacy of the combination of axatilimab, retifanlimab, and paclitaxel in patients with advanced solid tumors. SECONDARY OBJECTIVES: I. Determine the safety and tolerability of the combination of axatilimab, retifanlimab, and paclitaxel in patients with advanced solid tumors treated in phase II. II. Explore treatment related changes in the tumor microenvironment (TME) following treatment with the combination of axatilimab, retifanlimab, and paclitaxel in advanced solid tumors. III. Assess predictive biomarkers of response in peripheral blood. OUTLINE: Patients receive axatilimab intravenously (IV) over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 22 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, computed tomography (CT) scan, and blood sample collection throughout the study and may undergo magnetic resonance imaging (MRI) and/or positron emission tomography (PET) scan throughout the study. After completion of study treatment, patients are followed up at 30 and 90 days.
Investigators
Shivaani Kummar
Principal Investigator
OHSU Knight Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •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
- •Relapsed from, or refractory to, standard of care (SOC) systemic therapy known to prolong survival or if, in the opinion of the primary treating oncologist, a clinical trial is the best option for the next line of treatment based on response and/or tolerability to available therapies
- •Investigational therapy is permitted after a wash-out period of 5 half-lives (if known), or 28 days, whichever is shorter, prior to study day -
- •Prior use of an investigational agent for imaging, such as T cell imaging, is permitted
- •Prior treatment with taxanes. A wash-out of period of ≥ 3 months prior to day -8 must be met for enrollment. Prior anti PD-1/PD-L1 therapy is allowed, but not required
- •Eastern Cooperative Oncology Group (ECOG) status (performance status \[PS\]) of 0-1
- •Life expectancy of greater than 12 weeks according to certified physician review
Exclusion Criteria
- •Secondary malignancy with documented diagnosis by a treating physician \< 3 years prior to study day -
- •The following criteria also apply:
- •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
- •History of organ transplantation, including hematopoietic stem cell transplantation (HSCT)
- •Clinical evidence of interstitial lung disease or active non-infectious pneumonia
- •Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (≤ 10 mg/day of prednisone or equivalent is permitted)
- •Prior National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 immune-related adverse event (irAE) that required systemic immunosuppression (endocrinopathies managed by stable doses of supplements and/or corticosteroids ≤ 10 mg/day are permitted)
Arms & Interventions
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Axatilimab
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Biopsy
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Biospecimen Collection
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Computed Tomography
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Magnetic Resonance Imaging
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Paclitaxel
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Positron Emission Tomography
Treatment (axatilimab, retifanlimab, paclitaxel)
Patients receive axatilimab IV over 30 minutes on day -8, prior to cycle 1. Beginning in cycle 1 day 1, patients receive axatilimab IV over 30 minutes on days 8 and 21 of each cycle, retifanlimab IV over 30-60 minutes on day 1 of each cycle, and paclitaxel IV over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsy, CT scan, and blood sample collection throughout the study and may undergo MRI and/or PET scan throughout the study.
Intervention: Retifanlimab
Outcomes
Primary Outcomes
Incidence of dose limiting toxicities (phase Ib)
Time Frame: From the first dose of axatilimab (day -8) to the end of cycle 1 (cycle is 28 days starting from cycle 1 day 1 [first dose of retifanlimab and paclitaxel])
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)
Time Frame: From the first dose of axatilimab (day -8) to the end of cycle 1 (cycle is 28 days starting from cycle 1 day 1 [first dose of retifanlimab and paclitaxel])
Clinical benefit rate (phase Ib/II)
Time Frame: From screening assessment to the end of cycle 6 assessment (each cycle is 28 days starting from cycle 1 day 1 [first dose of retifanlimab and paclitaxel])
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.
Secondary Outcomes
- Change in immune cell population(From screening to end of treatment visit (an average of 6 months))
- Incidence of ≥ grade 3 toxicities possibly or definitely related to study drugs(From the first dose of axatilimab (day -8) to 90 days after the end of treatment visit (an average of 6 months))
- Changes in immune cell composition and functionality(From screening until cycle 2 day 1 biopsy (each cycle is 28 days starting from cycle 1 day 1 [first dose of retifanlimab and paclitaxel]))