Clinical trial NCT05178836: A Phase II Study to Evaluate the Efficacy and Safety of F520 Combined With F007 in Patients With RR DLBCL
Official title: An Open-label, Single-arm, and Multicenter Phase Ⅱ Study to Evaluate the Efficacay and Safety of F520 Combined With F007 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: RR DLBCL; PD-1; CD20
Lead sponsor: Shandong New Time Pharmaceutical Co., LTD
Sponsor class: INDUSTRY
First posted: 2022-01-05
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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, single-arm, and multicenter phase Ⅱ study designed to evaluate the efficacy and safety of F520 (PD-1) combined with F007(rituximab biosimilar) in patients with Relapsed/Refractory diffuse large B-cell lymphoma. About 62 patients with relapsed/refractory DLBCL plan to be enrolled in about 8 study sites of the study.

Primary objective:

The purpose is to evaluate the objective response rate of F520 combined with F007 in Relapsed/Refractory diffuse large B-cell lymphoma.

Secondary objective:

The purpose is to compare the safety of F520 combined with F007 in Relapsed/Refractory diffuse large B-cell lymphoma.


Eligibility criteria: Inclusion Criteria:

1. Aged ≥18 and ≤80 years old.
2. CD20-positive relapsed/refractory DLBCL (≥ 2 prior lines of therapy )

   Recurrence: Relapse occurred more than 6 months after the end of treatment. At least one regimen contains Rituximab.

   Refractory: Relapse within 6 months after the end of treatment or fail to reach PR after 2 treatment cycles and fail to reach CR after 4 treatment cycles. At least one regimen contains Rituximab.

   Recurrence after second-line treatment sequential autologous hematopoietic stem cell transplantation.
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
4. More than 3 months life expectancy.
5. Those who agree to provide archived tumor tissue samples or fresh tissue samples
6. Biopsy confirmed CD20-positive after the last treatment. Recurrence more than 1 year needs to undergo tissue biopsy to confirm the pathological diagnosis.
7. Adequate cardiac function (LVEF≥50%).
8. At least one measurable lesion:

   For intranodal lesions, the long diameter should be \>1.5cm; for extranodal lesions, the long diameter should be \>1.0cm.
9. Neutrophil count (NEUT) ≥1.5×109/L and platelet count (PLT) ≥75\*109/L and hemoglobin ≥75g/L, total bilirubin level (TBIL) ≤1.5×upper limit of normal (ULN), aspartic acid Aminotransferase (AST), alanine aminotransferase (ALT)≤2.5×ULN, creatinine level (Cr)≤1.5×ULN. Patients with liver metastases (TBIL≤3×ULN, ALT/AST≤5×ULN).
10. Signed an informed consent form which was approved by the institutional review board of the respective medical center.

Exclusion Criteria:

1. Primary mediastinal (thymic) large B-cell lymphoma.
2. Transformed lymphoma.
3. DLBCL invaded by special parts, such as central nervous system (CNS), testis, breast, ovary, etc.
4. High-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangement.
5. History of other malignancies (except for basal/squamous cell carcinoma of the skin, in-situ carcinoma of the cervix or breast, superficial bladder cancer, lung carcinoma in situ that have been cured for more than 5 years).
6. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV-DNA titer higher than 2000 IU/mL or 1000 copies) or hepatitis C virus (HCV). Treponema pallidum (TP) antibody positive.
7. Received systemic anticancer therapy include radiation, targeted therapy, or any other anticancer therapy within 3weeks or 5 half-lives before the first administration.
8. Participation in another clinical trial in the past 4 months.
9. Received allogeneic stem cell transplantation.
10. Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 antibody or other medications that stimulates or collaboratively inhibits T cell receptors or CAR-T.
11. Usage of immunosuppressive agents, systemic or local hormone therapy within 14 days before the first administration to achieve the purpose of immunosuppression (the daily dose is equivalent to systemic corticosteroids with prednisone\> 10 mg).
12. Vaccination with an attenuated live vaccine within 4 weeks before the first administration.
13. Suffered from interstitial pneumonia in the past 6 months.
14. Severe cardiovascular disease (New York Heart Association functional class III or IV, myocardial infarction or unstable arrhythmia or unstable angina in the last 6 months, severe cardiac insufficiency, rogressive multifocal leukoencephalopathy)
15. Uncontrolled hypertension (SBP≥180mmHg and/or DBP≥100mmHg).
16. Active autoimmune diseases, including but not limited to systemic lupus erythematosus, ankylosing spondylitis, etc.
17. Severe mental illness.
18. Known hypersensitivity to any of the study drugs or its ingredients.
19. Pregnant or lactating women.
20. The researcher believes that it is not suitable for enrollment.

Primary outcomes:
measure: 1. Objective response rate (ORR)
timeFrame: 16 weeks
Secondary outcomes:
measure: 1. Complete response rate (CRR)
timeFrame: 16 weeks
measure: 2. Progression-free survival (PFS)
timeFrame: 2 years
measure: 3. Duration of remission (DOR)
timeFrame: 2 years
measure: 4. Time to progression (TTP)
timeFrame: 2 years
measure: 5. Overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
References: