Combining Rocbrutinib with R-CHOP for Newly Diagnosed B-cell Non-Hodgkin Lymphoma

A Phase Ib Study to Assess Safety and Preliminary Efficacy of Rocbrutinib in Combination With R-CHOP in Patients With Newly Diagnosed B-NHL

This study is testing if adding a new drug called Rocbrutinib to the standard treatment for newly diagnosed B-cell Non-Hodgkin Lymphoma can help patients feel better and improve their outcomes.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 112 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. (industry)
• Drugs / interventions: Rituximab, ROCBRUTINIB, radiation, doxorubicin, Cyclophosphamide
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06251180 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter Phase Ib study evaluates the safety and preliminary efficacy of Rocbrutinib, a new generation Bruton Tyrosine Kinase inhibitor, in combination with R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, Prednisone) for adult patients with newly diagnosed, untreated B-cell Non-Hodgkin Lymphoma. The study consists of a dose escalation phase to determine the maximum tolerated dose and a dose expansion phase with three cohorts focusing on different lymphoma subtypes. Participants will receive treatment for six cycles followed by maintenance therapy with Rocbrutinib for two years, with follow-up assessments for up to five years.

Who should consider this trial

Good fit: Ideal candidates include adults with newly diagnosed, untreated B-cell Non-Hodgkin Lymphoma, specifically those with DLBCL, MZL, or MCL.

Not a fit: Patients who have previously received anti-tumor systemic therapy or local radiation therapy for their lymphoma will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with B-cell Non-Hodgkin Lymphoma by enhancing response rates and prolonging remission.

How similar studies have performed: Other studies have shown promising results with Bruton Tyrosine Kinase inhibitors in similar contexts, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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.
* International Prognostic Index (IPI) score ≥ 2 (only participants with DLBCL in dose expansion portion).
* Adequate coagulation, liver, kidney, and hematopoietic functions：PT and APTT \<1.5x ULN; serum bilirubin \<1.5x ULN except in participants with Gilbert's syndrome who must have a serum bilirubin of \<3x ULN, AST and ALT ≤ 3x ULN or \< 5x ULN if hepatic involvement are present; serum creatinine (Scr) ≤1.5 x ULN, or calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula.; ANC≥1500/mm3, hemoglobin≥8.0 g/dL, and platelets \>100,000/mm3 unless deemed related to lymphoma involvement in the bone marrow and felt potentially reversible by the treating physician.
* Women of childbearing potential must have a negative serum or urine (beta-human chorionic gonadotropin \[beta-hCG\]) at screening.
* Women of childbearing potential and men who are sexually active with a woman of childbearing potential must be practicing a highly effective contraceptive measures of during and after the study (90 days after the last dose of ROCBRUTINIB and 12 months after the last dose of Rituximab). Men must agree to not donate sperm during and for up to 90 days after he last dose of ROCBRUTINIB.
* Participants voluntarily enrolled and signed the informed consent form, and followed the trial treatment and visits.

Exclusion Criteria:

* 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.
* Major surgery within 4 weeks of study entry or expected major surgery during the study.
* Prior another non-antitumor or medical instruments clinical trials within 4 weeks.
* Known bleeding diseases (such as von Willebrand's disease or hemophilia A, hemophilia B, etc.), or have bleeding tendency.
* Prior treatment with warfarin or equivalent vitamin K antagonists within 14 days; requires anticoagulation with warfarin or equivalent vitamin K antagonists.
* Prior treatment with strong/moderate CYP3A4 inhibitors within 5 days or prior foods with inhibitory effects on CYP3A4 within 3 days at screening; requires chronic treatment with moderate/strong CYP3A inhibitors or inducers, or OATP1B1/OATP1B3 sensitive substrates during the study.
* Participants with other malignancies other than the target indications of this study within the past three years.
* Prior treatment with the cumulative dose of doxorubicin ≥150 mg/m2 (or other anthracyclines at doses converted based on cumulative cardiac toxicity)
* Any serious medical condition including but not limited to uncontrolled hypertension, uncontrolled congestive heart failure or ≥Class 2 cardiac disease as defined by the New York Heart Association Functional Classification or LVEF less than 40%, uncontrolled or symptomatic arrhythmias with corrected QT interval (QTc) \> 480 msec, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, COPD, renal failure, severe hepatic disease, uncontrolled active infection, active hemorrhage.
* Known HIV infection, or syphilis infection, or hepatitis B DNA or hepatitis C RNA positive.
* Known diseases that affect drug swallowing or absorption.
* Unfit to participate in this study in the investigator's opinion.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Yue Shen, Ph D

Conditions: B-cell Non-Hodgkin Lymphoma