Polivy (polatuzumab vedotin-piiq)

Our study demonstrates that our local population has similar clinicopathological and prognostic characteristics of DLBCL as compared to global findings. It also highlights the limitations of R-CHOP(-like) regimens in contemporary DLBCL management and therefore an ongoing need for improved therapeutic strategies.

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

ViPOR-P is safe without notable additional toxicity, especially neutropenia and neuropathy, compared to ViPOR, and DL3 was identified as the RP2D. Most AEs were hematologic and manageable with G-CSF with rare febrile neutropenia observed. 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.

P2, N=39, Recruiting, University of Rochester | Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2026

P2, N=622, Recruiting, Genmab | Trial completion date: Jun 2031 --> Nov 2032 | Trial primary completion date: Jun 2031 --> Nov 2032

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

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P2, N=80, Not yet recruiting, Navy General Hospital, Beijing

P1, N=174, Recruiting, Celgene | Trial primary completion date: Sep 2024 --> Dec 2024

Her initial treatment comprised chemo-free therapy and radiotherapy, followed by progression. In the second-line treatment, a Pola-based regimen was applied, and the patient achieved a complete response, suggesting that this regimen may be a therapeutic option for patients with DLBCL involving the central nervous system.

P=N/A, N=1000, Recruiting, Hoffmann-La Roche | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Sep 2026 --> Dec 2026

P3, N=1000, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jul 2024 --> Jul 2026 | Trial primary completion date: Jul 2024 --> Jul 2026

In a single center real world retrospective analysis of R/R LBCL patients with available genomic data, polatuzumab based therapy may be less effective in patients with HGBL-NOS or MYC/BCL2 histology and MYC rearrangements, but not in patients with GCB COO LBCL without these features. Routine performance of more comprehensive pathologic analysis of tumors may inform the use of polatuzumab based therapy in patients with LBCL.

Treatment with polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone has become the standard of care for newly diagnosed CD20-positive DLBCL with an International Prognostic Index score of 2 to 5, based on its reported efficacy for this indication. In addition, the development of immunotherapy such as anti-CD19-chimeric antigen receptor (CAR)-T therapy and bispecific antibodies such as epcoritamab, mosunetuzumab, and glofitamab has led to a paradigm shift in treatment of relapsed/refractory DLBCL. This review summarizes the evolution of treatment development for DLBCL, as well as the results of the current clinical standard of care and new therapies that are expected to become the standard of care.

P3, N=222, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting | Trial completion date: Nov 2027 --> Feb 2027 | Trial primary completion date: May 2025 --> Feb 2025

P2; N=31; Not yet recruiting; Sponsor:Medical College of Wisconsin

P2, N=3, Terminated, Academic and Community Cancer Research United | N=63 --> 3 | Trial completion date: Apr 2029 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2027 --> Mar 2024; Trial closed due to low accrual rate

P2, N=622, Recruiting, Genmab | N=394 --> 622 | Trial completion date: Nov 2032 --> Jun 2031 | Trial primary completion date: Nov 2032 --> Jun 2031

Signals for peripheral sensory neuropathy were 4.83, 2.44, 2.74, and 2.21 (calculated based on IC025) for brentuximab vedotin, trastuzumab emtansine, enfortumab vedotin, and polatuzumab vedotin, while signals for peripheral motor neuropathy were 5.31, 0.34, 2.27, and 0.03, respectively...Tisotumab vedotin had the highest hospitalization rate at 26.67%, followed by brentuximab vedotin at 25.5%...Brentuximab vedotin and enfortumab vedotin showed similar profiles for peripheral sensory neuropathy and motor neuropathy. Given the delayed time to onset and potentially poor outcomes, ADC-related peripheral neuropathy warrants significant attention.

P1, N=68, Recruiting, University of Washington | Suspended --> Recruiting

See related article by Corcoran et al., p. 1653 (6) See related article by Meriranta et al. (7).

In Japan, 4 drugs are approved as ADCs for leukemia and lymphoma: gemtuzumab ozogamicin(GO)consists of an anti-CD33 monoclonal antibody bound to calicheamicin via a linker, approved for relapsed/refractory acute myeloid leukemia. Brentuximab vedotin (BV)has anti-CD30 antibodies bound to MMAE via a linker and is approved for CD30-positive Hodgkin's lymphoma, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma...Inotuzumab ozogamicin(IO)has an anti-CD22 antibody bound to calicheamicin via a linker, approved for relapsed/refractory CD22-positive B-cell acute lymphoblastic leukemia...Polatuzumab vedotin(PV)has an anti-CD79b monoclonal antibody bounds to MMAE via a linker, approved for diffuse large B-cell lymphoma(DLBCL). In DLBCL patients with an international prognostic index score(IPI score)of 2 or higher, the combination of PV plus rituximab, cyclophosphamide, doxorubicin, and prednisone(PV+R-CHP)extended PFS at 2 years compared with R-CHOP(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), which has long been the standard of care. As shown, ADCs exhibit high therapeutic efficacy in leukemia and lymphoma treatment, but many aspects of their resistance mechanisms remain unclear and require further research.

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

P2, N=36, Recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P2, N=41, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Mar 2027 --> Mar 2028 | Trial primary completion date: Mar 2027 --> Mar 2028

P1, N=68, Suspended, University of Washington | N=50 --> 68

P3, N=100, Recruiting, Ruijin Hospital | Not yet recruiting --> Recruiting

P1, N=55, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2029 --> Oct 2030 | Trial primary completion date: Jul 2024 --> Oct 2025

Rituximab was the first one approved...Polatuzumab, a CD79b-targeting ADC, is approved as first-line treatment in high-risk patients in combination with chemo-immunotherapy...To date, two BsAbs (glofitamab and epcoritamab) are approved as monotherapy in third-line treatment in DLBCL. Combination strategies with chemotherapy, immunotherapy, and ADCs are currently under investigation with encouraging results in first-line or subsequent lines of treatment. In the following review, we focus on the structure of BsAbs, the mechanism of action, clinical efficacy, and the mechanisms of resistance to BsAbs.

P3, N=100, Not yet recruiting, Ruijin Hospital

P2, N=80, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting

P2, N=528, Not yet recruiting, The First Affiliated Hospital with Nanjing Medical University

P2, N=168, Active, not recruiting, Miltenyi Biomedicine GmbH | Recruiting --> Active, not recruiting

P=N/A, N=47, Not yet recruiting, Beijing Hospital; Beijing Hospital

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

P1, N=50, Terminated, Hoffmann-La Roche | Completed --> Terminated; Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the BO42203 study.

The median time to AEs occurrence following polatuzumab vedotin initiation was 18.5 (5∼57.75) days, with 95% of AEs occurred within 162 days. This study identified various AEs associated with polatuzumab vedotin, offering critical insights for clinical monitoring and risk identification in patients receiving polatuzumab vedotin therapy.

P2, N=20, Enrolling by invitation, The First Affiliated Hospital of Soochow University

P2, N=41, Not yet recruiting, City of Hope Medical Center

P2, N=152, Not yet recruiting, Ruijin Hospital

P1, N=30, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P1/2, N=188, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Aug 2023 --> Aug 2025