Denosumab and Pembrolizumab in Clear Cell Renal Carcinoma

Exclusion Criteria52

• Prior treatment with pembrolizumab, or with any other anti-PD-1, anti-PD-L1,
• Anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting
• T cell co-stimulation or immune checkpoint pathways
• Active autoimmune disease that has required systemic treatment in the past 2 years
• (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
• drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
• replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
• form of systemic treatment.
• Any condition requiring systemic treatment with either corticosteroids (>10mg daily
• prednisone or equivalent dose of alternative corticosteroid) or other
• immunosuppressive medications within 14 days of pembrolizumab administration.
• Intranasal, inhaled or topical steroids are permitted in the absence of active
• autoimmune disease.
• Prior treatment with denosumab.
• Untreated brain or leptomeningeal metastases or current clinical or radiological
• progression of known brain metastases, or requirement for steroid therapy for brain
• metastases. Patients with treated brain metastases are eligible if they have been
• stable and off steroids for over than or equal too 3 weeks.
• Prior allogeneic organ transplant, inflammatory bowel disease, pneumonitis,
• tuberculosis, or primary immunodeficiency
• Active infection requiring systemic therapy within 14 days before the first dose of
• pembrolizumab
• Receipt of live attenuated vaccination within 30 days of the planned first dose of
• pembrolizumab
• Active dental or jaw condition that precludes administration of denosumab:
• i) Significant dental/oral disease, including prior history or current evidence of
• osteonecrosis/osteomyelitis of the jaw, or; ii) Active dental or jaw condition which
• requires oral surgery, or; iii) Non-healed dental/oral surgery, or; iv) Planned
• invasive dental procedures during the course of the study
• Clinically significant hypersensitivity to denosumab or any components of denosumab
• Targeted small molecule therapy, surgery or radiation therapy within 2 weeks before
• registration, or persisting adverse event(s) of Grade 2 or more due to a previously
• administered agent. Note that participants who have had recent major surgery must have
• recovered adequately before registration.
• Life expectancy of less than 3 months.
• History of an active malignancy within the previous 5 years, except for locally
• curable cancers that have been apparently cured, such as low-grade thyroid carcinoma,
• prostate cancer not requiring treatment (Gleason grade less than or equal too 6), basal or squamous cell
• skin cancer, superficial bladder cancer, melanoma in situ, or carcinoma in situ of the
• prostate, cervix, or breast. Patients who have been free of other malignancies for greater than or equal than 5 years prior to registration are eligible for this study.
• Significant infection, including chronic active hepatitis B, hepatitis C, or HIV. -
• Serious medical or psychiatric conditions that might limit the ability of the patient
• to comply with the protocol
• Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal,
• infertile, or use a reliable means of contraception. Women of childbearing potential
• must have a negative pregnancy test done within 7 days prior to registration. Men must
• have been surgically sterilised or use a (double if required) barrier method of
• contraception. Subject is excluded if pregnant or breast feeding, or planning to
• become pregnant within 5 months after the end of treatment. Female subject of child
• bearing potential is excluded if they are not willing to use, in combination with her
• partner, highly effective contraception during treatment and for 5 months after the
• end of treatment.