Phase Ⅰ/Ⅱ Study of SHR2554 in Combination With SHR1701 in Patients With Advanced Solid Tumors and B-cell Lymphomas

Inclusion Criteria:

• 1. Age from 18 to 70 years with estimated life expectancy >3 months.
• 2. Histopathological confirmed locally advanced or metastatic systematically pretreated epidermal growth factor receptor (EGFR) / anaplastic lymphoma kinase (ALK) / c-ros oncogene 1 receptor kinase (ROS1) /BRAF negative non-small cell lung cancer (adenocarcinoma or squamous cell carcinoma), pancreatic adenocarcinoma, cholangiocarcinoma, gastrointestinal adenocarcinoma, triple-negative breast cancer and relapsed/refractory B-cell lymphoma (All enrolled subjects with above solid carcinoma are required to have received at least first-line systematic therapy and subjects with R/R B-cell lymphoma need a history of at least two lines of previous treatment; For solid carcinoma subjects enrolled in phase Ⅱ period, their previous treatment lines are limited to no more than four lines; Besides previously treated subjects, subjects with initially diagnosed pancreatic adenocarcinoma or cholangiocarcinoma are also eligible for enrollment in phase Ⅱ period).
• 3. Have at least one measurable target lesion, determined by the site study team based on RECIST 1.1 and immune related RECIST.
• 4. Fresh tumor samples or formalin-fixed paraffin embedded tumor archival samples within 3 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
• 5. Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
• 6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 1 at the time of enrollment.

• 7. Have adequate organ function, as defined in the table below, which should be confirmed within 2 weeks prior to the first dose of study drugs.

  • Leukocytes greater than or equal to 3.0 ×10^9/L.
  • Absolute neutrophil counts greater than or equal to 1.0 ×10^9/L.
  • Platelets greater than or equal to 100 ×10^9/L.
  • Hemoglobin greater than or equal to 90 g/L.
  • Total bilirubin less than or equal to 2 x ULN.
  • Serum albumin should be no less than 30 g/L.
  • Alanine aminotransferase or Aspartate aminotransferase less than 2 x Upper Limit of Normal (ULN).
  • Measured creatinine clearance ≥ 60 mL per min.
• 8. Previous treatment with anti-PD-1/PD-L1 antibodies or cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors are allowed.
• 9. Ability to understand and sign a written informed consent document.
• 10.Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.

Exclusion Criteria:

• 1. Active, known or suspected autoimmune diseases.
• 2. Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
• 3. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
• 4. History of severe hypersensitive reactions to other monoclonal antibodies.
• 5. History of allergy or intolerance to study drug components.
• 6. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• 7. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
• 8. Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
• 9. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
• 10. Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
• 11. Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
• 12. Vaccination within 30 days of study enrollment.
• 13. Active bleeding or known hemorrhagic tendency.
• 14. Subjects with unhealed surgical wounds for more than 30 days.
• 15. Being participating any other trials or withdraw within 4 weeks.