Polivy (polatuzumab vedotin-piiq)

We reveal how KLHL6 targets CD79B for degradation in normal and malignant germinal center B cells, thereby determining expression of the surface BCR complex. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic.

P1, N=50, Suspended, University of Washington | Recruiting --> Suspended

The phase III POLARIX study (NCT03274492) evaluated polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) as first-line treatment of diffuse large B-cell lymphoma (DLBCL). An increase of <50% in acMMAE/unconjugated MMAE exposure did not lead to a clinically meaningful increase in adverse events of special interest. ER data and the benefit-risk profile support the use of polatuzumab vedotin 1.8 mg/kg once every 3 weeks with R-CHP for six cycles in patients with previously untreated DLBCL.

P3, N=270, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Dec 2025 --> Mar 2025

P2, N=396, Recruiting, SWOG Cancer Research Network | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=99, Not yet recruiting, University College, London | Trial completion date: Jan 2028 --> Jul 2028 | Initiation date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2028 --> Jan 2027

P2, N=42, Recruiting, University of Washington | Trial completion date: Aug 2024 --> Dec 2025 | Trial primary completion date: Aug 2024 --> Dec 2025

P2, N=49, Recruiting, Barbara Ann Karmanos Cancer Institute | Trial completion date: Nov 2023 --> Nov 2026 | Trial primary completion date: Nov 2023 --> Nov 2025

P1/2, N=422, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Oct 2024 --> Jan 2024

P2, N=40, Not yet recruiting, University Health Network, Toronto | Initiation date: Dec 2023 --> Aug 2024

P1, N=50, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Feb 2024 --> Jun 2024

P2, N=168, Recruiting, Miltenyi Biomedicine GmbH | Trial completion date: Dec 2024 --> Jul 2027 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=41, Active, not recruiting, City of Hope Medical Center | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

P3, N=300, Recruiting, Nordic Lymphoma Group | N=200 --> 300 | Trial completion date: Feb 2026 --> Dec 2028 | Trial primary completion date: Feb 2023 --> Dec 2025

In treating diffuse large B-cell lymphoma (DLBCL), oncologists have traditionally relied on the chemotherapy backbone of R-CHOP as standard of care...With a replacement strategy, a breakthrough in treatment was identified with polatuzumab vedotin (anti-CD79B antibody/drug conjugate) plus R-CHP...Thus, we aim to highlight the challenges of DLBCL therapy as well as the need to address therapeutic regimens eventually no longer tethered to a chemotherapy backbone. In the intersection of artificial intelligence and multi-omics (genomics, epigenomics, transcriptomics, proteomics, metabolomics), we propose the need to analyze multidimensional biologic datato launch a decisive attack against DLBCL in a targeted and individualized fashion.

P1/2, N=280, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2024 --> Sep 2026 | Trial primary completion date: Nov 2024 --> Sep 2026 | Recruiting --> Active, not recruiting

SN8 is the antibody component of polatuzumab vedotin, an anti-CD79b antibody drug conjugate, that has been widely used for therapy of diffuse large B-cell lymphoma (DLBCL)...Furthermore, simultaneous targeting of PD-1 strongly potentiates CD79a/CD79b-targeted therapy of B cell tumors. Flow cytometry analyses of CD79a/CD79b on malignant B cells of patients may provide a method for selection of the candidate patients for the CD79a/CD79b dual targeting therapy.

P2, N=394, Recruiting, AbbVie | Trial completion date: May 2029 --> Nov 2032 | Trial primary completion date: May 2029 --> Nov 2032

P2, N=20, Recruiting, Weill Medical College of Cornell University

P2, N=44, Recruiting, UNC Lineberger Comprehensive Cancer Center

P2, N=66, Recruiting, Christine Ryan | Initiation date: Oct 2023 --> Apr 2024

P1, N=174, Recruiting, Celgene | Phase classification: P1b --> P1

P1, N=30, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: May 2025 --> Dec 2025 | Initiation date: Dec 2023 --> Sep 2024 | Trial primary completion date: May 2025 --> Dec 2025

P1/2, N=114, Completed, Hoffmann-La Roche | Phase classification: P1 --> P1/2

P1/2, N=188, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

P1, N=200, Recruiting, ADC Therapeutics S.A. | Phase classification: P1b --> P1

P2, N=30, Recruiting, Yan Zhang, MD

We performed an SLR to understand the efficacy and real-world (RW) effectiveness of non–CAR T-cell therapies for R/R LBCL including tafasitamab with lenalidomide (tafa/len), polatuzumab with bendamustine/rituximab (pola-BR), loncastuximab, selinexor, epcoritamab, and glofitamab. Currently, the evidence base, particularly RW studies, for non–CAR T-cell R/R LBCL therapies is still limited. In comparison, 78 RW CAR T-cell therapy studies were published (Jacobson et al. Tandem Meeting.

These data demonstrate that mosunetuzumab plus polatuzumab vedotin has a favorable safety profile with highly durable responses suitable as second-line therapy in transplant-ineligible relapsed/refractory LBCL. ClinicalTrials.gov identifier: NCT03671018 .

P2, N=150, Not yet recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Oct 2028 --> Jan 2029 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2028 --> Jan 2029

P1, N=50, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

NEJM 2022)POLARIX trial has shown that first-line treatment with the Pola-R-CHP combination, showed a progression-free survival benefit over the R-CHOP regimen at 2 years and had a similar safety profile, other prospective therapeutic trials have shown benefit of polatuzumab based therapy in Relapsed/Refactory DLBCL. Polatuzumab vedotin has emerged as an innovative therapeutic option in the management of DBLCL. The experience in developing countries is limited and the outcomes, unexplored. In our study, Pola-R-CHP ORR was 66.

A micro-costing analysis was developed to compare practice efficiency of treating patients with R/R DLBCL using epcoritamab versus comparator treatments (glofitamab, polatuzumab/bendamustine/rituximab [pola-BR], tafasitamab/lenalidomide [tafa-len], and axicabtagene ciloleucel [axi-cel]) over a time horizon of up to 1 year. Due to its unique SC administration, epcoritamab improves institutional practice efficiency despite more frequent dosing, saving personnel costs and inpatient costs. This could help to alleviate capacity constraints at infusion centers and ease patient scheduling. The resources saved (staff time, chair time, inpatient monitoring) can be redirected to other institutional needs, improving the availability and quality of healthcare services for patients.

Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine (Lonca), polatuzumab vedotin + bendamustine + rituximab (Pola-BR), rituximab + gemcitabine + oxaliplatin (R-GemOx), tafasitamab + lenalidomide, and epcoritamab. Over 3 years, the estimated cumulative per-patient cost of glofitamab is projected to be the lowest when compared with per-patient costs of other available T-cell engaging therapies, resulting in cost savings after its formulary adoption for the treatment of R/R DLBCL after ≥2 lines of therapy.

In 5 trials (N=204), 13 patients with Pola + atezolizumab (Ate) + obinutuzumab (Obi), 49 patients with Pola + Obi + venetoclax (Ven), 39 patients with Pola + Obi, 62 with Pola + Obi + lenalidomide (Len), and 20 patients with Pola + rituximab (Rit)...(N=41), Pola + Rit was compared with pinatuzumab vedotin (Pina) + Rit... Pola was well tolerated by most of the patients with FL alone or in combination with Obi, Rit, Len, Ven. Pola had relatively better response and survival rates as compared to Pina in combination with Rit. In early phase clinical trials, three drug regimens of Pola and Obi with Ven, and Len were effective in the treatment of heavily pretreated follicular lymphoma.

GCB subtype has better prognosis, but 20% of patients still relapsed after R-CHOP therapy (Nowakowski GS,2015), and no more benefit was achieved by modifying regimen with new agents like polatuzumab-R-CHP (Tilly H,2022), adding on lenalidomide (Nowakowski GS,2015) or ibrutinib (Wilson WH,2021)...Patients were administered selinexor 60mg QW in combination with standard R-CHOP therapy for 6 cycles (Rituximab 375 mg/m 2, cyclophosphamide 750 mg/m 2, doxorubicin 50 mg/m 2 IV, vincristine 0. 5 mg/kg on day 1, prednisone 100 mg PO on days 1-5 in a 21-day cycle)...ConclusionOnce weekly 60mg selinexor can be safely combined with R-CHOP in ND high risk (IPI 3-5) GCB subtype DLBCL patients with ORR of 100% and CR of 60%. No viral reactivation was observed in patients with viral hepatitis with simultaneous antiviral therapy.

We observed a statistically significant difference by log-rank in OS2 in patients receiving platinum-based salvage chemotherapy followed by autologous stem cell transplant compared to other therapies in a contemporary cohort of pts with RR DLBCL. This difference is likely driven in part by transplant being a surrogate marker for efficacy of salvage chemotherapy. OS3 was also highest at 12, 24, and 60 months in patients receiving platinum-based salvage chemotherapy followed by transplant.

, 2020)Patients with DLBCL are typically treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)...In the POLARIX phase 3 trial, polatuzumab vedotin (a monoclonal antibody to CD79b ubiquitously expressed on B cells) combined with R-CHP significantly improved 2 year progression-free survival compared to the routine R-CHOP therapy in previously untreated DLBCL patients...In conclusion, primary pulmonary DLBCL is a rare entity with only a few case reports in literature. It should be considered in patients presenting with large pulmonary masses, mimicking metastatic disease.

It is recently available in China and approved in combination with Bendamustine and Rituximab for r/r DLBCL. gov (NCT05940051) . We illustrated the flowchart of our study in Figure 2.

7%) chidamide, 8 (13...0%) polatuzumab, 1 (1...Adverse events were generally manageable with appropriate supportive care and dose modification. These data are generally consistent with the SADAL study and supports the use of selinexor as an oral, chemotherapy-free treatment option for R/R DLBCL patients in China.

In the phase 3 PHOENIX trial of pts with DLBCL, the addition of ibrutinib to R-CHOP failed to improve overall outcomes. The addition of zanubrutinib to R-CHOP is well tolerated and does not compromise R-CHOP delivery. Given the recent approval of polatuzumab in combination with R-CHP in DLBCL, and no additional toxicity concerns identified in this phase Ib trial, the protocol is being amended to substitute polatuzumab for vincristine.

Therefore, the use of targeted drugs and the exploration of drug combination schemes are particularly important, among them, anti-CD79B antibody-drug conjugate (ADC) polatuzumab vedotin (Pola) combined with Bendamustine-Rituximab (BR) and Pola combined with R-CHOP are promising therapeutic options. The main adverse event was a pulmonary infection, of which 33% (4/12) were in the Polar-BR group and 25% (1/5) were in the Polar-R-CHOP group, and no severe pneumonia occurred in either group. Conclusion Compared with the traditional R-CHOP regimen, Polar+BR/RCHOP has better therapeutic effect and a better application prospects for R/R DLBCL patients.