Zanubrutinib plus obinutuzumab and lenalidomide for first-line follicular lymphoma

A Prospective, Open-label, Single-arm Multicenter Clinical Study of Zanubrutinib, Obinutuzumab, and Lenalidomide (ZGR) in the Treatment of Untreated Follicular Lymphoma

This trial tests whether the combination of zanubrutinib, obinutuzumab, and lenalidomide is safe and effective as a chemotherapy-free first treatment for adults with untreated follicular lymphoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: obinutuzumab, zanubrutinib, prednisone, rituximab, ibrutinib, chemotherapy
• Locations: 2 sites (Tianjin, Tianjin Municipality and 1 other locations)
• Trial ID: NCT07299149 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, single-arm trial in a Chinese population testing a chemotherapy-free triple regimen of a BTK inhibitor (zanubrutinib), an anti-CD20 antibody (obinutuzumab), and lenalidomide given as induction followed by maintenance with zanubrutinib and lenalidomide. Participants must have histologically confirmed CD20-positive follicular lymphoma (Grade 1–3A) and meet standard criteria for starting therapy. The study will measure antitumor activity (response rates and durability) and safety to characterize efficacy and tolerability of this combination. Archived or fresh tumor tissue for immunohistochemistry is required and patients will be followed for treatment response and adverse events.

Who should consider this trial

Good fit: Adults (≥18 years) with previously untreated, CD20-positive follicular lymphoma (Grade 1–3A) who require therapy because of stage II bulky or stage III/IV disease and can provide required tissue samples are ideal candidates.

Not a fit: Patients with transformed disease, Grade 3B follicular lymphoma, prior lymphoma therapy, or medical conditions that prevent receiving these agents are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this chemo-free combination could provide strong tumor control while reducing chemotherapy-related toxicity and improving patients' quality of life.

How similar studies have performed: Lenalidomide plus anti-CD20 antibodies (R2 or O-Len) have shown activity in frontline FL and several studies combining BTK inhibitors with R2 have been promising, but full triple regimens like zanubrutinib + obinutuzumab + lenalidomide remain less well studied.

Eligibility criteria

Inclusion Criteria:

* Gender: No restrictions; age ≥18 years.
* Diagnosis: Histologically confirmed CD20-positive follicular lymphoma (FL), Grade 1, 2, or 3A, per 2016 WHO classification. All patients must provide sufficient archived or fresh tumor tissue samples for immunohistochemical (IHC) analysis.
* Disease Stage \& Treatment Need:
* Stage III or IV disease, or Stage II with bulky disease, meeting at least one of the following criteria:
* a) Bulky disease: Lymph node or extranodal (excluding spleen) mass with maximum diameter ≥7 cm.
* b) Local symptoms or organ dysfunction due to progressive lymphadenopathy or extranodal tumor mass.
* c) B symptoms (fever, night sweats, or unintentional weight loss \>10% of body weight within ≤6 months).
* d) Symptomatic extranodal involvement (e.g., pleural/peritoneal effusion).
* e) Cytopenias due to bone marrow infiltration (hemoglobin \<10 g/dL, absolute neutrophil count \[ANC\] \<1.0×10⁹/L, platelets \<100×10⁹/L).
* f) Involvement of ≥3 lymph nodes, each ≥3 cm in diameter.
* g) Symptomatic splenomegaly.
* Prior Therapy: No prior systemic therapy for FL.
* ECOG Performance Status: ≤2.
* Measurable Disease: At least one measurable lesion (\>2 cm in longest diameter by CT/MRI).
* Life Expectancy: ≥6 months.
* Adequate Organ Function:
* a) ANC ≥1.0×10⁹/L (without growth factor support).
* b) Platelets ≥50×10⁹/L (untransfused within 7 days).
* c) Total bilirubin (TBIL) ≤1.5×ULN.
* d) ALT/AST ≤3×ULN.
* e) Creatinine clearance ≥30 mL/min (calculated by modified Cockcroft-Gault formula).
* Contraception: Men and women of childbearing potential must agree to use highly effective contraception during the study and for 4 weeks after treatment discontinuation.
* Informed Consent: Patients must voluntarily participate and sign informed consent forms (ICF).

Exclusion Criteria:

* Patients meeting any of the following criteria will be excluded from this study:
* Histologic evidence of central nervous system (CNS) lymphoma, leptomeningeal lymphoma, or transformation to high-grade lymphoma (e.g., diffuse large B-cell lymphoma, DLBCL).
* Grade 3B follicular lymphoma (FL) or transformed FL.
* Ann Arbor Stage I FL.
* Prior history of malignancy, unless the patient has been disease-free for ≥5 years and the treating physician deems the risk of recurrence low (exceptions: non-melanoma skin cancer, cured localized prostate cancer, carcinoma in situ of the cervix, or squamous intraepithelial lesions on PAP smear).
* Use of any investigational drugs, antibiotics, or participation in another interventional clinical trial within 4 weeks prior to enrollment.
* Major surgery (excluding lymph node biopsy) within 14 days before enrollment or anticipated need for major surgery during the study.
* Prior treatment with zanubrutinib, obinutuzumab, or lenalidomide.
* Immunodeficiency or autoimmune disease history, or chronic systemic steroid therapy (\>10 mg/day prednisone equivalent) or immunosuppressive therapy within 7 days before enrollment.
* Severe hepatic dysfunction (including severe jaundice, hepatic encephalopathy, refractory ascites, or hepatorenal syndrome), cachexia, or multi-organ failure with renal impairment.
* Clinically significant cardiovascular abnormalities:
* NYHA Class III/IV heart failure
* Myocardial infarction within 6 months before enrollment, Malignant arrhythmias (including QTc ≥480 ms), Uncontrolled hypertension (Systolic blood pressure (SBP) ≥150 mmHg and diastolic blood pressure (DBP) ≥100 mmHg), Unstable angina.

Active infections:

* HIV, active hepatitis B/C infection (HBV DNA ≥2000 IU/mL or HCV RNA detectable)
* Uncontrolled systemic infections.
* Bleeding disorders or coagulation abnormalities, or thrombotic events within 3 months.
* Severe hypersensitivity to the active ingredients or excipients of the study drugs.
* Pregnancy, lactation, or unwillingness to use effective contraception in women of childbearing potential.
* Other conditions deemed unsuitable by the investigator.

Where this trial is running

Tianjin, Tianjin Municipality and 1 other locations

• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences, Tianjin, Tianjin 300020 — Tianjin, Tianjin Municipality, China (NOT_YET_RECRUITING)
• Institute of Hematology and Blood Diseases Hospital ,Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Shuhua Yi — Institute of Hematology & Blood Diseases Hospital, China
• Study coordinator: Shuhua Yi, Dr

Conditions: Follicular Lymphoma, follicular lymphoma, zanubrutinib, Obinutuzumab, lenalidomide