Efficacy of Immunotherapy Plus a Drug in Patients With Progressive Advanced Mucosal Cancer of Different Locations

Exclusion Criteria

• •1. Prior treatment with anti-PD-1/PD-L1 agents or histone deacetylases (HDAC) inhibitors.
• •2. Patients with central nervous system involvement that has not been controlled for \>3 months.
• •3. Patients with no other site for biopsy than bone lesions.
• •4. Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including uncontrolled diabetes, cardiac disease, uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infection within one year, chronic liver or renal disease, active gastrointestinal tract ulceration, severely impaired lung function.
• •5. Known history of human immunodeficiency virus (HIV), Hepatitis B virus (HBV; defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (HCV; defined as HCV RNA detected) virus infection.
• •6. History of autoimmune disease with the exception of:
• •* (1) Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone,
• •* (2) Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen,
• •* (3) Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) provided that they meet the following conditions: (i) Rash must cover less than 10% of body surface area; (ii) Disease is well controlled at baseline and only requiring low potency topical steroids; (iii) No acute exacerbations of underlying condition within the previous 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoid, biologic agents, oral calcineurin inhibitors, high-potency or oral steroids).
• •7. History of allogeneic organ or bone marrow transplantation.
• •8. History of non-infectious pneumonitis that required steroids or has current pneumonitis.
• •9. Has an active infection requiring systemic therapy.
• •10. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• •11. Known prior severe hypersensitivity to investigational products or its excipients,
• •12. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to first dose of study treatments.
• •Note: Participants must have recovered from all adverse events due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
• •13. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system disease.
• •14. Major surgery within 28 days prior to the first dose of study treatments. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• •15. Current or prior use of immunosuppressive medication within 7 days before the first dose of pembrolizumab. The following are exceptions to this criterion:
• •* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection),
• •* Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or its equivalent,
• •* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• •16. Patients using drugs that could have pharmacokinetics interaction with investigational drugs. This includes, but is not limited to, valproic acid, coumarin-derivative anticoagulants, drugs that disrupt electrolyte levels, drugs that may prolong QT.
• •17. Pregnant women or women who are breast-feeding.
• •18. Patients enrolled in another therapeutic study within 30 days prior to inclusion and during the treatment period. Patients can participate in an independent approved non-interventional studies.
• •19. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
• •20. Persons deprived of their liberty or under protective custody or guardianship