This is an open-label, multicentre Phase Ib study to evaluate the safety and preliminary efficacy of new generation Bruton Tyrosine Kinase inhibitor Rocbrutinib in combination to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, Prednison) in adult patients with newly diagnosed, previously untreated B-cell Non-Hodgkin Lymphoma \[Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL) or Mantle Cell Lymphoma (MCL)\].
Participants was histopathologically diagnosed with any of the following diseases: DLBCL, MZL or MCL (if enrolled in the dose expansion phase, histological confirmation of non-GCB subtype), and have not previously received anti-tumor systemic therapy or local radiation therapy for the above diseases.
Participants must have at least one measurable lesion.
ECOG physical status score 0-2.
Life expectancy ≥6 months.
Participants are allergic to Rocbrutinib or any of its excipients; Participants who are assessed by the investigator as being unable to tolerate the R-CHOP regimen.
Participants with known central nervous system involvement with lymphoma. or diagnosis of primary central nervous system lymphoma (PCNSL) or primary mediastinal large B-cell lymphoma (PMBL).
Participants with DLBCL had a history of indolent lymphoma such as FL or CLL (Richter's transformation), or was histopathologically comfirmed with FL (regardless of grade) coexistentially.
Prior treatment with solid organ transplantation or hematopoietic stem cell transplantation(HSCT) ; expected HSCT during the study.
Single group
Rocbrutinib
Drugorally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.
Rituximab
Biological/Vaccine375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.
Cyclophosphamide
Drug750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
doxorubicin
Drug50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Vincristin
Drug1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Prednisone
Drug100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.
MTD
Standard phase I 3+3 design.
Recommended Dose
Recommended Dose will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
Incidence of AEs
Type, frequency and severity of AEs, relationship of AEs to study treatment Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Type, frequency and severity of AEs, relationship of AEs to study treatment Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
Incidence of clinically significant laboratory abnormalities
Clinically significant abnormalities in hematology, chemistry, coagulation and urinalysis.
Objective Response Rate (ORR)
Assessment using the Lugano Response Criteria for Malignant Lymphoma.
Complete remission (CR)
Assessment using the Lugano Response Criteria for Malignant Lymphoma.
Duration of Response(DOR)
DOR is defined as the number of days from the date of the first remission to the date of earliest disease progression or death.
Progression-Free Survival(PFS)
PFS is defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death.
Click on the lead sponsor to view all of their trials.
