Gazyva (obinutuzumab)

P1/2, N=65, Recruiting, Hoffmann-La Roche | Trial primary completion date: Oct 2027 --> Mar 2027

P1, N=121, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2028 --> Mar 2029 | Trial primary completion date: Jul 2026 --> Mar 2027

P2, N=12, Completed, Bnai Zion Medical Center | Active, not recruiting --> Completed

AVO was highly active and well-tolerated in patients with previously untreated CLL with high-risk CLL, supporting its use as a new standard of care treatment option.

P1/2, N=860, Recruiting, Hoffmann-La Roche | Trial completion date: Aug 2025 --> Aug 2026 | Trial primary completion date: Aug 2025 --> Aug 2026

P3, N=1080, Recruiting, Genmab | Trial completion date: May 2037 --> Nov 2037 | Trial primary completion date: May 2037 --> Nov 2037

At present, studies at home and abroad have confirmed that the 90-minute short duration infusion of obinutuzumab is safe and feasible.In order to improve the convenience of patient infusion and the efficiency of medical institutions'infusion facilities, it is recommended for patients who do not experience grade ≥3 infusion-related adverse reactions in the first cycle of obinutuzumab infusion at the standard rate, a short duration infusion scheme should be used for subsequent treatment courses. This expert consensus is formulated to provide guidance for clinical practice.

Patients will receive obinutuzumab 2000 mg IV on C1D1-2, followed by glofitamab step-up dosing of 2.5 mg IV on C1D8, 10 mg on C1D15, and 30 mg on day 1 of C2-12 (21-day cycles). In the current trial we evaluate a regimen which we anticipate will be tolerable and highly active in R/R MCL, with the potential for MRD-guided limited-duration therapy. The trial is currently open for enrollment at UCSF and is expected to open at multiple centers through the University of California Hematologic Malignancies Consortium.

Clinical trials that studied the combination of the first generation BTKi ibrutinib and V have shown the feasibility and efficacy of the regimen. Given the favorable safety profile and sustained efficacy of acalabrutinib, combination regimens with venetoclax without (AV) or with obinutuzumab [O] (AVO) have been studied in the first line setting, and favorable efficacy and safety have been reported...Patients with significant cardiovascular disease, absorption issues, active bleeding or history of bleeding diathesis or required/currently receiving anticoagulation with warfarin or equivalent vitamin K antagonists were excluded...Clinical responses including uMRD4 at the end of treatment and the safety profile will be assessed. The trial is actively enrolling at Fred Hutchinson Cancer Center/University of Washington.

Introduction : The combination of venetoclax, the first-generation BCL2 inhibitor, and ibrutinib, a BTK inhibitor, has demonstrated efficacy in patients with chronic lymphocytic leukemia (CLL) (Wierda et al. Other secondary endpoints include PFS as assessed by investigator (INV); CRR by INV; rate of uMRD4 based on flow cytometry; overall response rate by IRC and INV; duration of response by IRC and INV; patient-reported outcomes; and safety and tolerability. Recruitment is ongoing at approximately 230 study sites in 20 countries, including 50 sites in the US, 6 in Brazil, and 15 in Canada.

P2, N=30, Suspended, C. Babis Andreadis | N=50 --> 30 | Recruiting --> Suspended

P1, N=50, Recruiting, Hoffmann-La Roche | Not yet recruiting --> Recruiting

P1/2, N=316, Recruiting, Simcha IL-18, Inc. | Active, not recruiting --> Recruiting | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Jun 2025

P2, N=15, Active, not recruiting, Bnai Zion Medical Center | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2024 --> Dec 2024

Six weeks later, while receiving the CD20-directed immunotherapies glofitamab and obinutuzumab, another bone marrow biopsy revealed eradication of the B-ALL and new involvement by pure erythroid leukemia (PEL). This patient's B-ALL lacked an IGH::BCL2 fusion resulting from t(14; 18), suggesting it did not arise through transformation of his prior FL/DLBCL. Instead, the B-ALL was likely caused by his extensive exposure to genotoxic chemotherapy drugs – including alkylating agents – for his preceding lymphomas. The shared cytogenetic and molecular features between this patient's B-ALL and PEL imply they are clonally related.

P2, N=170, Not yet recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=125, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Recruiting | N=80 --> 125 | Trial primary completion date: Sep 2027 --> Apr 2025

All pts received obinutuzumab pretreatment (1000mg or 2000mg) on Cycle (C) 1 Day (D) 1. Conclusions : Glofitamab induces high response rates in pts with heavily pretreated R/R MCL, including those who have clinical and/or histological features associated with poor prognosis. Clinical and molecular remissions are achieved early in the course of treatment, with durable responses lasting beyond the length of the treatment.

The combination of the Bruton tyrosine kinase inhibitor (BTKi) ibrutinib, the BCL-2 inhibitor venetoclax (V), and the anti-CD20 monoclonal antibody (mAb) obinutuzumab (O) has demonstrated safety and efficacy in R/R and TN MCL (Le Gouill, Blood 2021). Conclusions : AVO is safe and active in pts with R/R and TP53-aberrant/transplant ineligible TN MCL. Preliminary efficacy and feasibility of an MRD-guided treatment approach is encouraging in this high-risk TN cohort B. Our data supports further investigation of a targeted triplet approach, and the phase II TN transplant eligible and TP53 wild type cohort is enrolling based on demonstrated safety and efficacy in cohort B. Updated results will be presented at the meeting.

Responses are durable, with 89%, 87%, and 77% 4-yr PFS in all-comer, uIGHV, and TP53 aberrant pts. Our data support further study of AVO for pts with TN high risk CLL in GCLLSG CLL16 and future trials.

Zanubrutinib is a second-generation BTKi with superior PFS and safety compared with ibrutinib (Brown NEJM 2023). Retreatment with zanubrutinib-venetoclax was also well-tolerated and effective. A phase 2 trial of BOVen with ΔMRD400-directed treatment duration is ongoing.

Deep uMRD was revealed by ClonoSeq® in 12 out of 13 (92%) of pts tested. These data support the use of VO as a time-limited treatment option in both academic and community settings for CLL pts initiating frontline therapy.

Fixed-duration ViPOR-P x 6C without maintenance resulted in durable CRs, especially in pts with non-GCB DLBCL by IHC and ABC DLBCL by RNA-seq, including refractory and post-CAR-T pts. Molecular and MRD analyses are ongoing, and enrollment continues to assess whether ViPOR-P improves CR rate compared to ViPOR alone in R/R non-GCB DLBCL.

ViPOR with a 12d VEN ramp-up on C2 is safe in MCL pts of all ages without significant TLS or febrile neutropenia. Enrollment continues to better define the response and durability of ViPOR in MCL.

The ALO regimen is feasible with encouraging initial safety and efficacy. MRD and cfDNA analyses provide real-time and non-invasive monitoring of molecular response and mutational evolution, which warrants further evaluation in response-adapted strategy (ClinicalTrials.gov - NCT03863184).

In this study, concordance rate between PB and BM was relatively low (approximately two-thirds concordance) at 10-6 (C9) and 10-5 (C12) sensitivities. Longer follow-up from this study will inform the impact of PB and BM MRD status on PFS and if additional Ven/Obin beyond 12C improves outcomes for those who remain dMRD.

Introduction : Combined treatment with covalent BTK-inhibitor (cBTKi), such as ibrutinib, acalabrutinib, or zanubrutinib with BCL2-inhibitor, venetoclax, +/- CD20 monoclonal antibody obinutuzumab showed high rates of undetectable MRD (U-MRD4, 10-4 sensitivity) remission in patients (pts) with CLL (Jain, NEJM 2019; Munir NEJM 2023; Wierda, JCO 2021; Kater, NEJM Evidence 2022). Adverse event profile was similar to what was noted in previous studies with these agents. Updated data will be presented.

We present the 6-year update of a phase 2 study evaluating the combination of obinutuzumab and idelalisib in relapse/refractory Waldenstrom macroglobulinemia. Moreover, ibrutinib remains an effective treatment after this combination. This study was registered on the clinicaltrial.gov web (NCT02962401, November 9, 2016).

P2, N=42, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Mar 2025 | Trial primary completion date: Dec 2025 --> Mar 2025

Accordingly, analysis of patients with CLL that were treated with venetoclax or the anti-CD20 antibody obinutuzumab exhibited marked elevation of BAFF and increased pro-survival proteins in leukemic cells that persisted. Overall, these data highlight the rapid adaptation of CLL cells to targeted therapies via homeostatic factors and support co-targeting of cytokine signals to achieve deeper and more durable long-term responses.

P1, N=119, Completed, BeiGene | Phase classification: P1b --> P1

P=N/A, N=200, Not yet recruiting, Ruijin Hospital

P2, N=29, Not yet recruiting, Ruijin Hospital

P2, N=106, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting

These data support its use and further evaluation of the BOVen regimen in this high-risk population. NCT03824483.

P2, N=75, Recruiting, AbbVie | Trial primary completion date: Nov 2026 --> Feb 2025

P4, N=60, Not yet recruiting, AstraZeneca

P2, N=120, Not yet recruiting, National Cancer Institute (NCI)

P3, N=300, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

P1, N=203, Terminated, Gilead Sciences | Active, not recruiting --> Terminated; The goal of the study was to improve tolerability while maintaining or increasing efficacy. The results of this study showed no efficacy advantage although the combinations were well tolerated.

P2, N=100, Not yet recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Dec 2031 --> Mar 2032 | Initiation date: Sep 2024 --> Dec 2024 | Trial primary completion date: Feb 2028 --> May 2028

Tailored chemo-free regimens can be selected based on age, comorbidities, IGHV status, and cytogenetic abnormalities to optimize treatment outcomes while considering different response spectra.