Patient case: 48-year-old female with melanoma; genetic feature: tumor cells with >50% membranous PD-L1 expression

Clinical trial: The Safety, Pharmacokinetics and Antitumor Activity of the BGB-A317 in Combination With the BGB-290 in Subjects With Advanced Solid Tumors

Summary: The Safety, Pharmacokinetics and Antitumor Activity of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With the PARP Inhibitor BGB-290 in Subjects With Advanced Solid Tumors


Eligibility: Inclusion Criteria:
  1. Subjects have voluntarily agreed to participate by giving written informed consent.
  2. Subjects have advanced tumor who failed at least 1 prior chemotherapy.
  3. In Part A, the subjects must have a histologically or cytologically confirmed advanced tumor.
  4. In Part B, the subjects recruited to one of the four expansion arms must have histologically or cytologically confirmed advanced solid tumor with BRCA1/2 mutation or with documented HR or MMR deficiency.
  5. Subjects must have measurable disease as defined per the RECIST version 1.1.
  6. Male or female ≥ 18 years of age on the day of signing informed consent.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1.
  8. Life expectancy ≥ 12 weeks.
  9. Subject must have adequate organ function as indicated by the following laboratory values.
  1. Absolute neutrophil count (ANC) ≥ 1,500/mL
  2. Platelets ≥ 100,000/mL
  3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
  4. Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
  5. Serum total bilirubin ≤ 1.5 × ULN (On fractionation ≤ 90% of total bilirubin should be unconjugated).
  6. Aspartate aminotransferase (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with liver metastases
  7. International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN
  8. Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
  10. Female subjects are eligible to enter and participate in the study if they are of:
  1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant)
  2. Childbearing potential, has a negative serum pregnancy test at screening (within 7 days of the first investigational product administration), is not breast feeding, and uses adequate contraception before study entry and throughout the study until 90 days after the last investigational product administration.
  11. Male subjects are eligible to enter and participate in the study if they are vasectomized or agree to use of contraception during the study treatment period and for at least 180 days after the last dose of the study drug.
  Exclusion Criteria:
  1. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)
  2. Prior malignancy within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast
  3. Prior therapies targeting PD-1, programmed death-ligand 1 (PD-L1), or PARP
  4. Subjects with active autoimmune diseases or history of autoimmune diseases should be excluded;
  5. Subjects should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of the study drug administration.
  6. Has history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies.
  7. Known history of human immunodeficiency virus (HIV);
  8. Active infection requiring therapy, positive tests for hepatitis B surface antigen (HBsAg) or hepatitis C ribonucleic acid (RNA);
  9. Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events (AEs);
  10. Inability to swallow oral medications (capsules and tablets) without chewing, breaking, crushing, opening or otherwise altering the product formulation.
  11. Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies used to control cancer must have been completed at least 4 weeks or at least 5 half-lives (whichever is shorter) before the study drug administration, and all AEs have either returned to baseline or stabilized.
  12. Use of any vaccines (e.g., against infectious diseases such as influenza and varicella) within 4 weeks (28 days) of initiation of study therapy and 60 days after the last administration of the study medication.

Relevance to patient case: not relevant