Patient case: 49-year-old male with melanoma; genetic feature: extensive tumor infiltrating lymphocytes

Clinical trial: A Study to Evaluate the Safety and Tolerability of Using the SHR-1210 by Advanced Melanoma Subjects

Summary: This is an open-label, single center, non-randomized, dose escalation phase I trial to evaluate safety and tolerability of SHR-1210 in patients with advanced Melanoma. The primary objective is to assess safety and tolerability of SHR-1210 and identify recommended phase II doses of SHR-1210 in patients with advanced Melanoma.

Detailed description: This is an open-label, single center, nonrandomized, dose-escalation Phase 1 study to evaluate safety and tolerability of SHR-1210 in subjects with advanced Melanoma who have failed current standard antitumor therapies.
  The safety and tolerability of SHR-1210 will be assessed by ongoing reviews of clinical laboratory tests, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, electrocardiogram (ECG), and adverse events. Evaluations of immune safety will also be conducted (immune-related adverse events (AEs), or labs of autoimmune sera, inflammatory events, and immunogenicity). Safety evaluations (both clinical and laboratory) are performed at baseline, before each study treatment, and throughout the study.
  Efficacy will be assessed every 8 weeks. The study consists of 3 periods: screening (up to 14 days before the first dose), treatment, and follow-up (up to 3 months after the last dose of study treatment).

Eligibility: Inclusion Criteria:
  1. Male or female 18-70 years of age.
  2. Subjects diagnosed with histologically or cytologically confirmed Melanoma documented as advanced or metastatic disease. Subjects must be considered relapsed or refractory to standard therapies, have been intolerant to standard therapies, or have refused standard therapy.
  3. ECOG performance status of 0 or 1.
  4. Life expectancy ≥ 12 weeks.
  5. Subjects enrolled in the Part 2 expansion cohorts must have measurable lesion(s) according to response evaluation criteria in solid (RECIST) v1.1.
  6. Adequate laboratory parameters during the screening period as evidenced by the following:
  1. Absolute neutrophil count ≥ 1.5 × 109/L (1500/mm3)
  2. Platelets ≥ 100 × 109/L (100,000/mm3)
  3. Hemoglobin ≥ 9.0 g/dL (90 g/L)
  4. Albumin (ALB) levels ≥ 2.8 g/dL
  5. Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN)
  6. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; for subjects with liver metastases, ALT and AST ≤ 5 × ULN
  Serum creatinine ≤ 1.5 × ULN
  7. Female subjects agree not to be pregnant or lactating from beginning of the study screening through at least 3 months after receiving the last dose of study treatment. Both men and women of reproductive potential must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy. A highly effective method of contraception is defined as one that results in a low failure rate, that is, less than 1% per year when used consistently and correctly
  8. Able to understand and sign an informed consent form (ICF).
  Exclusion Criteria:
  1. Subjects with any active autoimmune disease or history of autoimmune disease, or history of syndrome that requires systemic steroids or immunosuppressive medications, including but not limited to the following: rheumatoid arthritis, pneumonitis, colitis (inflammatory bowel disease), hepatitis, hypophysitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Subjects with the following conditions will not be excluded from this study: asthma that requires intermittent use of bronchodilators, hypothyroidism stable on hormone replacement, vitiligo, Graves' disease, or Hashimoto's disease. Additional exceptions may be made with medical monitor approval.
  2. Known history of hypersensitivity to any components of the SHR-1210 formulation.
  3. Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
  4. Active central nervous system (CNS) metastases (indicated by clinical symptoms, cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging [MRI] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
  5. Uncontrolled clinically significant medical condition, including but not limited to the following: (1) congestive heart failure (New York Health Authority Class > 2), (2) unstable angina, (3) myocardial infarction within the past 12 months, or (4) clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention.
  6. Prior systemic chemotherapy (< 6 weeks if chemotherapy including nitrosoureas or mitomycin), radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of any stable chronic toxicities not expected to resolve).
  7. Active infection or an unexplained fever > 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, subjects with tumor fever may be enrolled).
  8. History of immunodeficiency including seropositivity for human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease.
  9. Any other medical (eg, pulmonary, metabolic, congenital, endocrinal, or CNS disease), psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
  10. Investigational therapy administered within 4 weeks before the first dose of SHR-1210.
  11. History of PD-1 antibody therapy or other therapy that focuses on the Immune regulation receptor .
  12. History of psychotropic substance abuse, alcoholism or drug abuse.
  13. Other factors that may lead to the termination of the participation in the study at the discretion of the investigators.

Relevance to patient case: not relevant