Clinical trial NCT03155425: PD-1 Antibody SHR-1210 in Patients With Relapsed or Refractory Classic Hodgkin's Lymphoma
Official title: An Open-Label, Single Arm, Multi-Center, Phase 2 Study of PD-1 Antibody SHR-1210 in Subjects With Relapsed or Refractory Classic Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Lymphoma, Adult
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, non-randomized, phase 2 trial to evaluate efficacy and safety of SHR-1210 in patients with relapsed or refractory classic Hodgkin's lymphoma. The primary objective is to assess ORR of SHR-1210 in patients with relapsed or refractory classic Hodgkin's lymphoma.

Detailed description: The primary objective of this phase 2 study is to assess objective response rate of SHR-1210 in patients with relapsed or refractory classic Hodgkin's lymphoma. The secondary objective is to observe the duration of response, progression free survival, time to response, overall survival and safety of SHR-1210 in relapsed or refractory classic Hodgkin's lymphoma. Pharmacokinetic index is also investigated in 12 patients.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed classic Hodgkin's lymphoma;
2. Relapsed or refractory cHL and meet any of the following criterions: a) did not achieve remission or progression after autologous hematopoietic stem cell transplantation. b) at least 2 lines of systemic chemotherapy and are not suitable for autologous stem cell transplantation;
3. Subjects enrolled have measurable lesion (s) according to Lugano 2014 criteria;
4. ECOG performance status of 0 or 1;
5. Life expectancy ≥ 12 weeks;
6. Adequate laboratory parameters during the screening period as evidenced by the following:

   1. Absolute neutrophil count ≥ 1.0 × 109/L;
   2. Platelets ≥ 75 × 109/L;
   3. Hemoglobin ≥ 8.0 g/dL;
   4. Total bilirubin (TBIL) \< 1.5 × upper limit of normal (ULN), ALT and AST ≤ 2.5×ULN;
   5. Serum Creatinine ≤1.25×ULN or Creatinine clearance≥45 mL/min;
   6. Coagulation function index: INR ≤1.5×ULN，APTT≤1.5×ULN;
7. Women of childbearing potential (WOCBP) must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy while on treatment and for at least 60 days after receiving the last dose of study treatment. Women of childbearing potential with pregnancy test negative within 7 days before entering the group; male subjects with WOCBP partner should receive Surgical sterilization or consent to employ a highly effective method of birth control/contraception to prevent pregnancy while on treatment and for at least 120 days after receiving the last dose of study treatment;
8. Able to understand and sign an informed consent form (ICF).

Exclusion Criteria:

1. Known nodular lymphoma predominant Hodgkin lymphoma or Grey zone lymphoma.
2. Known central nervous system lymphoma.
3. History and complication:

(1) Active, known or suspected autoimmune disease. Subjects who were in a stable state without systemic immunosuppressive therapy were admitted; (2) Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic corticosteroids \> 10mg; doses \> 10 mg/day topical prednisone or equivalent are prohibited within 2 weeks before entering the group; (3) Received anti-tumor vaccines or other anti-tumor therapy with immune stimulation within 3 months before the first dose SHR-1210; (4) Prior exposure to any PD-1/PD-L1/PD -L 2 or CTLA -4 antibody; (5) Participating in other clinical studies or less than 4 weeks before the end of a clinical trial; (6) Known and highly Suspicion of interstitial pneumonia; (7) Other active malignancies that required treating. (subjects with skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma or cervical carcinoma who had no disease recurrence within 5 years after the start of treatment were excluded); (8) Received chemotherapy, radiotherapy, immunotherapy, including topical therapy within 4 weeks. Previous anti-tumor therapy related adverse reactions (except hair loss) did not recover to CTCAE ≤1; (9) Prior allo-HSCT; (10) ASCT within 90 days; (11) Impact of major surgery or severe trauma had been eliminated for less than 14 days; (12) Active pulmonary tuberculosis; (13) Severe acute or chronic infection requiring systemic therapy; (14) Suffering from heart failure (New York Heart Association standard III and given appropriate medical treatment. Uncontrolled coronary artery disease and arrhythmia. History of myocardial infarction within 6 months; (15) Inoculated with live vaccine within 4 weeks before receiving the investigational drug. Injections of inactivated influenza vaccine for seasonal influenza are permitted, but not live attenuated influenza vaccines for intranasal use.

4. laboratory test:

(1) known HIV positive or known AIDS; (2) Untreated active hepatitis; co-infection with hepatitis B and hepatitis C.

5. Other factors that may lead to the study termination, such as severe disease or abnormal laboratory tests or family or social factors affecting subjects safety or test data and sample collection.

Primary outcomes:
measure: ORR Assess by IRC
timeFrame: CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. ORR of 36 weeks based on CT and PET were reported.
Secondary outcomes:
measure: DoR Assess by IRC
timeFrame: CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. DoR of 36 weeks based on CT and PET were reported.
measure: PFS Assess by IRC
timeFrame: Up to 3 years
measure: TTR Assess by IRC
timeFrame: CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25.
measure: OS
timeFrame: Up to 3 years
measure: Incidence and Severity of Adverse Events (AE)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
Study officials:
affiliation: Jiangsu Hengrui Pharmaceutical Co., Ltd.
name: Zhenyu Xiao, MD
role: STUDY_DIRECTOR
References:
citation: Song Y, Wu J, Chen X, Lin T, Cao J, Liu Y, Zhao Y, Jin J, Huang H, Hu J, Luo J, Zhang L, Xue H, Zhang Q, Wang W, Chen C, Feng J, Zhu J. A Single-Arm, Multicenter, Phase II Study of Camrelizumab in Relapsed or Refractory Classical Hodgkin Lymphoma. Clin Cancer Res. 2019 Dec 15;25(24):7363-7369. doi: 10.1158/1078-0432.CCR-19-1680. Epub 2019 Aug 16.