NCT05073250

IBI376 Plus Rituximab in Patients With Untreated Indolent Lymphoma.

IBI376 Plus Rituximab in Patients With Untreated Indolent Lymphoma：a Single-center, Open-label, Phase II Clinical Trial.（REPLY Study）

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Chinese PLA General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are the most common inert non Hodgkin's lymphoma (iNHL). The standard first-line treatment of advanced FL / MZL is based on rituximab. Whether combined with chemotherapy or not, iNHL can induce lasting remission, but most of it is usually incurable. Therefore, early treatment of advanced iNHL should focus on protecting the bone marrow function of patients. Although the first-line immunochemotherapy offer high efficacy but also high incidence of toxicity. Phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in the occurrence and development of B-cell malignant tumors. Studies have shown that PI3K inhibitor alone has good antitumor effect and tolerance in patients with recurrent refractory iNHL. In addition, PI3K inhibitor combined with rituximab showed better prognosis compared with rituximab monotherapy in FL / MZL patients. Therefore, the chemo-free regime, PI3K inhibitor in combination with rituximab may explore a new avenue for FL and MZL patients.

Detailed description

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are the most common inert non Hodgkin's lymphoma (iNHL). Their natural courses are slow but highly variable. The standard first-line treatment of advanced FL / MZL is based on rituximab. Whether combined with chemotherapy or not, it can induce lasting remission, but it is usually incurable. Although the first-line immunochemotherapy regimen has high efficacy, it also has high toxicity. Cytotoxic chemotherapy is related to many side effects, including bone marrow suppression and immunosuppression, gastrointestinal and cardiac toxicity, neurotoxicity and the occurrence of secondary tumors. About 20% of FL patients relapse within 2 years after first-line chemotherapy. The overall prognosis of these patients is poor. The median age of FL / MZL diagnosis is over 60 years old. These patients cannot tolerate conventional immunochemotherapy due to old age or complications. Compared with young and non complicated patients, the long-term survival is significantly reduced. Phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in the occurrence and development of B-cell malignant tumors. IBI376 (INCB050465) is a second generation, effective and highly selective PI3Kδ inhibitor. Recently, the results of two key phase II clinical trials of CITADEL-203 and CITADEL-204 show that IBI376 monotherapy has a rapid and long-lasting high response rate in patients with recurrent or refractory iNHL, and is safe and tolerable. In addition, the CRONOS-3 study showed that copanlisib, an intravenous pan class I PI3K inhibitor, combined with rituximab showed better progression free survival and clinically significant improvement in objective remission rate compared with standard rituximab monotherapy in FL / MZL patients. In conclusion, we speculate that the chemotherapy free regimen of IBI376 combined with rituximab may produce deep and lasting remission in patients with FL and MZL. This is a single center, open label, single arm phase II clinical trial, which is divided into cohort A (follicular lymphoma) and cohort B (marginal zone lymphoma). The two cohorts are carried out at the same time. A total of 40 patients were treated with IBI376 combined with rituximab. The primary objective of this study is to assess the feasibility of PI3K inhibitor IBI376 in combination with rituximab in patients with untreated FL and MZL. The primary objective of this study is to assess the feasibility of PI3K inhibitor IBI376 in combination with rituximab in patients with untreated FL and MZL. The exploratory objective is to evaluate the clinical predictive biomarkers for efficacy.

Conditions

• Inert Non Hodgkin's Lymphoma

Interventions

Type	Name	Description
DRUG	IBI376	IBI376 is administered orally once daily at a dose of 20 mg for 8 weeks, followed by an oral dose of 2.5 mg once daily. Patients assessed as PR after 6 cycles of induction therapy will receive another 6 cycles of IBI376 at an oral dose of 2.5 mg once daily.
BIOLOGICAL	Rituximab	Rituximab is administered at a dose of 375 mg/m\^2 intravenously in the first 4 weeks, once a week. Subsequently, rituximab will be dosed once every 4 weeks. Patients assessed as PR after 6 cycles of induction therapy will receive another 6 cycles of rituximab at a dose of 375 mg/m\^2 intravenously once every 4 weeks.

Timeline

• Start date: 2021-12-31
• Primary completion: 2023-12-31
• Completion: 2024-11-01
• First posted: 2021-10-11
• Last updated: 2023-05-12

Locations

1 site across 1 country: China