A Phase III Study to Evaluate the Efficacy and Safety of Penpulimab in the Relapsed and Refractory Classical Hodgkin's Lymphoma

Exclusion Criteria

• •1. Nodular lymphocytes are non-Hodgkin's lymphoma or gray area lymphoma.
• •2. Central nervous system lymphoma invasion.
• •3. Have received any investigational treatment or investigational device within 4 weeks prior to the first dose of study treatment.
• •4. Enrolled in another clinical study at the same time, unless it is an observational (non-interventional) clinical study or in follow-up period for interventional studies.
• •5. The last radiotherapy or last anti-tumor therapy (chemotherapy, tumor embolization, etc.) has been given within 4 weeks prior to the first dose of study treatment.
• •6. Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTLA-4 antibody, or any other antibody or drug target for T cell co-stimulatory or checkpoint pathways, such as ICOS or agonists (e.g., CD40, CD137, GITR and OX40, etc.).
• •7. Subjects with other malignancy within 5 years prior to the first dose of study treatment, except for locally curable cancers that have been apparently cured, such as basal or skin squamous cell carcinoma, superficial bladder cancer, cervix or breast carcinoma in situ.
• •8. Active, known or suspected autoimmune disease, or medical history of autoimmune disease in the past 2 years, with the exceptions of vitiligo, alopecia, graves' disease, psoriasis or eczema not requiring systemic treatment within the last 2 years, asymptomatic but only steady doses of hormone replacement therapy are required for hypothyroidism (caused by autoimmune thyroiditis) or type I diabetes requiring only a steady dose of insulin replacement therapy, or that the primary disease does not relapse without external triggering factors
• •9. Systemic glucocorticoids or other immunosuppressive drugs used within 7 days prior to the first dose of study treatment. It is allowed to use nasal spray, inhaled, or other topical application of glucocorticoids, and a physiological dose of systemic glucocorticoids does not exceed 10 mg/ day or the equivalent. Glucocorticoids are also allowed to temporary use for the treatment of dyspnea symptoms of chronic obstructive pulmonary disease (COPD), or as a prophylactic agent for hypersensitivity reactions.
• •10. Known active human immunodeficiency virus (HIV) positive.
• •11. Known history of primary immunodeficiency.
• •12. Known active tuberculosis.
• •13. Prior solid organ transplantation, allogeneic hematopoietic stem cell transplantation (HSCT).
• •14. ASCT within 90 days prior to the first dose of study treatment.
• •15. History of gastrointestinal perforation and/ or fistula (patients can be enrolled if the gastrointestinal perforation or fistula has been surgically removed), ileus (including incomplete ileus requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis or chronic diarrhea within 6 months prior to the first dose of study treatment.
• •16. Known history of or active interstitial lung disease (ILD) or ILD needs to use corticosteroids.
• •17. Patients with untreated chronic hepatitis B virus (HBV) infection or chronic HBV carriers with HBV DNA exceeding 500 IU/ mL, or hepatitis C virus (HCV) infection. Patients with non-active HBsAg carriers, treated and stable (HBV DNA \<500 IU/ mL), and cured HCV infection can be enrolled. Patients with HCV seropositivity are eligible only if the HCV RNA test negative.
• •18. Major surgery (craniotomy, thoracotomy, or laparotomy) performed within 30 days prior to the first dose of study treatment, or not fully recovered from previous surgery. Local procedures (such as systemic placement of ports, prostate biopsy) are allowed, provided that which are completed at least 24 hours prior to the first dose of study treatment.
• •19. Subjects with uncontrolled pleural effusion or ascites.
• •20. Active infection requiring systemic treatment.
• •21. Uncontrolled concurrent conditions, including but not limited to persistent or active infection, symptomatic congestive heart failure (NYHA grade 3 or 4), uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg), unstable angina, arrhythmia, or other mental illness/social conditions may limit the subject's compliance with the study requirements or impair the ability of the subject to provide written informed consent.
• •22. Known history of arterial or venous thrombosis events within 6 months prior to the first dose of study treatment, including myocardial infarction, unstable angina, and cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any other severe thromboembolism. Except for infusion port or catheter-derived thrombosis, or superficial venous thrombosis, or thrombosis that keep stable after conventional anticoagulant therapy.
• •24. Have received live or attenuated vaccine(s) within 30 days prior to the first dose of study treatment, or plan to receive live or attenuated vaccine(s) during the study.
• •25. Known allergy to any components or any ingredients of penpulimab and chemotherapy agents selected by investigator.
• •26. Pregnant or lactating women.
• •27. Subjects with NCI CTCAE v5.0 Grade ≥2 peripheral neuropathy.
• •28. Any conditions that evaluated by investigator may affect subjects' safety, or may interfere with the evaluation of study drug, or may confound the interpretation of study results.
• •29. Uncontrolled metabolic disorders, local or systemic manifestations either due to concomitant disease or the primary tumor, with high risk and/or uncertainty in survival evaluation, such as tumor leukemoid reaction (white blood cell count \> 20×109/L), cachexia (known weight loss of more than 10% in the 3 months before screening), etc.