Evaluating Combination of Nivolumab and Axatilimab in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Exclusion Criteria

• •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug.
• •--Of note, the following are allowed:
• •* The use of physiologic doses of corticosteroids (i.e., ≤10 mg per day of equivalent prednisone) is allowed.
• •* Steroids with no or minimal systemic effect (topical, inhalation) are allowed.
• •* Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• •* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• •Previously treated with a CSF-1, CSF-1R, and/or IL-34-blocking agents.
• •History of Grade ≥3 immune-mediated adverse event attributed to prior immune checkpoint-inhibitor therapy that has not resolved with steroids; other than endocrinopathy managed with replacement therapy.
• •--All immune-mediated adverse events related to prior cancer immunotherapy must be resolved per Investigator.
• •History of autoimmune disease, including, but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis, with the following exceptions:
• •--Autoimmune hypothyroidism on stable dose of thyroid replacement, controlled Type 1 Diabetes Mellitus on insulin, history of disease-related ITP or AIHA, or remote history of or well-controlled autoimmune disease with treatment-free interval from immunosuppressive therapy for at least 12 months.
• •History or current clinically significant pulmonary disease, such as obstructive pulmonary disease, bronchospasm, or non-infectious pneumonitis (drug-induced or autoimmune).
• •Prior systemic anti-cancer therapy or any investigational therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter. Patients are allowed to be actively receiving anti-PD-1(anti-PD-L1) therapy at the time of enrollment but must stop agents other than Nivolumab prior to dosing with Nivolumab.
• •Evidence of muscle disorders or muscle injury that are known to cause serum creatine kinase (CK) elevation
• •History of PML, HLH, CNS vasculitis, uncontrolled seizure disorder, or neurodegenerative disease.
• •Allogeneic stem cell transplant within 90 days prior to screening or on current treatment for graft vs host disease
• •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks or palliative radiation therapy within 2 weeks of the first dose of study drug.
• •Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery.
• •The diagnosis of another malignancy within ≤ 2 years before study enrollment, except for those considered to be adequately treated with no evidence of disease or symptoms and/or will not require therapy during the study duration (i.e., basal cell or squamous cell skin cancer, carcinoma in situ of the breast, bladder or of the cervix, or low-grade prostate cancer with Gleason Score ≤ 6).
• •Known brain metastases or cranial epidural disease.
• •--Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
• •Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• •* Cardiovascular disorders:
• •* Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
• •* Stroke, myocardial infarction (MI), or other ischemic events within 3 months before the first dose.
• •* QTc prolongation defined as a QTcF \> 500 ms.
• •* Known congenital long QT.
• •* Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, \[subjects may not receive the drug through a feeding tube\], social/ psychological issues, etc.)
• •Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
• •--Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
• •Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice).
• •Clinically significant liver disease, including viral or other hepatitis or cirrhosis.
• •--Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• •Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
• •Known prior severe hypersensitivity to nivolumab or SNDX-6352 or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
• •Subjects taking prohibited medications as described in Section 6. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.