Clinical trial NCT05896046: SHR1701 Alone or in Combination With SHR2554 in Relapsed or Refractory Classical Hodgkin Lymphoma
Official title: An Open-Label Phase I/II Study of SHR1701 Alone or in Combination With SHR2554 in Relapsed or Refractory Classical Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Hodgkin Lymphoma
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2023-06-09
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is an open-label, phase I/II dose escalation and expansion trial. The primary objective of dose escalation phase I study is to evaluate the safety and feasibility of SHR1701 in patients with relapsed or refractory classical Hodgkin Lymphoma. The primary objective of open-label, randomized, phase II study is to assess the antitumor effect of SHR1701 alone or in combination with SHR2554 in patients with relapsed or refractory classical Hodgkin Lymphoma.

Detailed description: In phase I study, patients received intravenous SHR1701 30-150 mg/kg every 3 weeks. Sequential patient groups received the following doses of SHR1701: 30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg, or 150 mg/kg in a 3+3 design with the intention of determining the recommended dose for phase 2. Toxicities are graded according to the Common Terminology Criteria for Adverse Events, version 5.0.

In phase II expansion study, based on the recommended dose of SHR1701 from phase I study, patients are treated with SHR1701 alone if CR rate is satisfactory, or randomized to SHR1701 monotherapy group or SHR2554 plus SHR1701 combination group to assess the clinical efficacy of SHR2554 plus SHR1701 combination therapy.

Eligibility criteria: Inclusion Criteria:

1. Subjects must have histological confirmation of relapsed or refractory Hodgkin lymphoma (HL).
2. 12 to 75 years of age.
3. ECOG performance of less than 2.
4. Life expectancy of at least 3 months.
5. Subjects with lymphoma must have at least one measureable lesion \>1 cm as defined by lymphoma response criteria.
6. Subjects must have received two or more lines of previous therapy, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months. Previous treatment with anti-PD-1/PD-L1 antibodies or cytotoxic T lymphocyte associated antigen 4 (CTLA-4) inhibitors are allowed, and must be off therapy for at least 4 weeks.
7. Subjects must have adequate marrow, live, renal and heart functions.

Exclusion Criteria:

1. Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
2. Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
3. Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
4. Prior organ allograft.
5. Women who are pregnant or breastfeeding.
6. Women with a positive pregnancy test on enrollment or prior to investigational product administration.
7. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Primary outcomes:
measure: Phase I : Adverse events
timeFrame: Up to 90 days after the last dose of study drugs
measure: Phase I/ II: Complete response rate (CRR)
timeFrame: up to 36 months
Secondary outcomes:
measure: Phase II: Objective response rate (ORR)
timeFrame: up to 36 months
measure: Phase II: Progression-free survival (PFS)
timeFrame: up to 36 months
measure: Phase II: Overal survival
timeFrame: up to 36 months
measure: Phase II: Duration of response (DOR)
timeFrame: up to 36 months
Other outcomes:
measure: Phase II: Biomarkers predictive of efficacy and toxicity
timeFrame: up to 36 months
Locations:
city: Beijing
country: China
facility: Han wei dong
state: Beijing
Study officials:
References: