Clinical Trials

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of malignancy with demonstrated progression of a solid tumor (non-lymphoma) with no alternative standard-of-care therapeutic option (certain exceptions may apply).
2. At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment (certain exceptions may apply).
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
   1. Note: Patients with ECOG PS >1 are ineligible.
4. ≥18 years old..

• Hepatic function:
  • Total bilirubin ≤1.5 x upper limit of normal (ULN; if liver metastases ≤3 ULN, or HCC ≤3 x ULN in non-docetaxel containing cohorts-only). Patients with Gilbert’s Disease and total bilirubin up to 3 x ULN may be eligible after  communication with and approval from medical monitor.
  • Transaminases ≤3 ULN  (or 5.0 ULN, if liver metastases or HCC)
  • Alkaline phosphatase (ALP) ≤2.5 ULN (or ≤5.0 ULN, if liver or bone metastases, or HCC)
  • For patients with hepatic metastases or hepatic malignancies, exclude patients with concomitant 3 x ULN ≤ aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤5 x ULN AND 1.5 x ULN ≤ total bilirubin ≤3 x ULN
• Renal function: Serum creatinine ≤1.5ULN creatinine clearance (CrCl) >50 ml/min
• Bone marrow function:
  • Hemoglobin ≥9.0 g/dL
  • ANC ≥1.5 x 109/L
  • Platelet count ≥75 x109/L
    • Note: For Expansion Cohort 13 (hepatocellular cancer), the platelet count requirement is ≥60 x 109/L.
• Ability to provide signed informed consent

Exclusion Criteria:

• Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only hormone replacement or psoriasis that does not require systemic treatment.
• Prior treatment with an agent that blocks the programmed death-1/ programmed death-ligand 1 (PD-1/PD-L1 pathway) (certain exceptions may apply).
• Prior treatment with other immune modulating agents within fewer than 4 weeks prior to the first dose of REGN2810. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB (CD137), OX-40, therapeutic vaccines, or cytokine treatments.
• Untreated brain metastasis(es) that may be considered active. Patients with previously treated brain metastases may participate provided they are stable (ie, without evidence of progression by imaging for at least 6 weeks prior to the first dose of study treatment, and any neurologic symptoms have returned to baseline), and there is no evidence of new or enlarging brain metastases, and the patient does not require any systemic corticosteroids for management of brain metastases within 4 weeks prior to the first dose of cemiplimab (certain exceptions may apply).
• Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab.
• The information provided above is not intended to contain all considerations relevant to potential participation in a clinical trial ,therefore not all inclusion/ exclusion criteria are listed.
• Active infection requiring therapy, including known infection with human immunodeficiency virus, or active infection with hepatitis B or hepatitis C virus, except for designated cohorts that allow hepatitis or HIV (Patients with hepatitis B on antiviral therapy or patients with hepatitis C may be eligible for the HCC expansion cohort (Cohort 13), but HCC patients with co-infection of hepatitis B and C are excluded. Patients with HIV may enroll only into Expansion Cohort 20. Patients with HIV  and hepatitis B on antiviral therapy and patients with HIV and hepatitis C may enroll into Cohort 20 if all other criteria are met).
• History of pneumonitis within the last 5 years.
• Any investigational or antitumor systemic treatment within 4 weeks prior to the initial administration of cemiplimab. Patients on gonadotropin-releasing hormone (GnRH) agonists (e.g., for prostate cancer) are not excluded. Patients receiving  bisphosphonates or denosumab are not excluded.
• History of documented allergic reactions or acute hypersensitivity reaction attributed to treatment with antibody therapies in general, or to agents specifically used in the study.
• Known allergy to doxycycline or tetracycline (precaution due to presence of trace components in cemiplimab).
• Known hypersensitivity to cyclophosphamide for patients enrolled in cohorts receiving cyclophosphamide.
• Breast-feeding.
• Positive serum pregnancy test. (A false positive pregnancy test, if demonstrated by serial measurements and negative ultrasound, will not be exclusionary, upon communication with and approval from the medical monitor).
• History within the last 5 years of an invasive malignancy other than the one treated in this study and/or any leukemia or lymphoma, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast, or history of prostate adenocarcinoma treated with curative intent at least 3 years ago, and with undetectable prostate-specific antigen for at least 3 years prior to enrollment or other local tumors considered cured by local treatment, upon communication with and approval from the medical monitor.
• Acute or chronic psychiatric problems that, under the evaluation of the investigator, make the patient ineligible for participation.
• Continued sexual activity in men** or women of childbearing potential*** who are unwilling to practice highly effective contraception during the study and until 6 months after the last dose of study drug (highly effective contraceptive measures include stable use of oral contraceptives such as combined estrogen and progestogen and progestogen only hormonal contraception or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; intrauterine hormone-releasing system (IUS); bilateral tubal ligation; vasectomy and sexual abstinence.
  • ** Contraception is not required for men with documented vasectomy.
  • *** Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.
• For patients enrolled in cohorts receiving GM-CSF, known hypersensitivity to GM-CSF, yeast–derived products, or any component of the product.
• For patients enrolled in the cohort containing carboplatin, history of hypersensitivity reaction to carboplatin (Grade ≥2 allergic reaction).
• For patients enrolled in a cohort containing docetaxel, history of hypersensitivity reaction to docetaxel (Grade ≥2 allergic reaction).
• Patients with a history of solid organ transplant (patients with prior corneal transplant may be allowed to enroll following discussion and approval from the medical monitor).