Epkinly (epcoritamab-bysp)

P1, N=30, Not yet recruiting, National Heart, Lung, and Blood Institute (NHLBI)

P2, N=184, Recruiting, Genmab | Trial primary completion date: Aug 2027 --> May 2029

P1, N=15, Recruiting, Genmab | Trial primary completion date: Nov 2028 --> Jun 2027

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

P1, N=26, Not yet recruiting, Timothy Voorhees

P2, N=32, Recruiting, Dipenkumar Modi | Trial completion date: Jun 2025 --> Nov 2028 | Trial primary completion date: Sep 2024 --> Nov 2027

P2, N=31, Recruiting, Abramson Cancer Center at Penn Medicine | Not yet recruiting --> Recruiting

CD3 × CD20 BsAbs have shown the most promise in clinical development for B-NHL patients, with structural variations affecting their target affinity and potency. This review summarizes the current clinical trials of BsAbs for relapsed/refractory FL, highlighting the approval of some agents, their role in first-line treatment or combination therapies, their toxicity profiles, and the future of this therapeutic approach compared to other immune cell therapies.

P3, N=1080, Recruiting, Genmab | Trial primary completion date: Jan 2030 --> May 2037

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.

P2, N=120, Recruiting, Academic and Community Cancer Research United | Not yet recruiting --> Recruiting

P3, N=320, Recruiting, Genmab | Not yet recruiting --> Recruiting

P1, N=20, Not yet recruiting, Paolo Caimi, MD | Initiation date: Aug 2024 --> Dec 2024

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

Adequate hydration and dexamethasone as the preferred steroid for mandatory CRS prophylaxis were recommended in C1. Rate and severity of CRS were substantially reduced with C1 OPT. These results support continued evaluation of epcoritamab tx in the outpatient setting.

P1, N=15, Recruiting, Genmab | Trial primary completion date: Jun 2027 --> Nov 2028

P2, N=33, Not yet recruiting, City of Hope Medical Center

P2, N=24, Not yet recruiting, Reid Merryman, MD

P2, N=39, Recruiting, Australasian Leukaemia and Lymphoma Group (ALLG) | Not yet recruiting --> Recruiting

This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.

P2, N=40, Recruiting, Peter MacCallum Cancer Centre, Australia | Not yet recruiting --> Recruiting

P1/2, N=49, Active, not recruiting, Genmab | Trial completion date: Dec 2024 --> Apr 2025 | Trial primary completion date: Dec 2024 --> Apr 2025

P3, N=900, Recruiting, Genmab | Trial primary completion date: Aug 2026 --> Sep 2028

P3, N=1080, Recruiting, Genmab | Trial primary completion date: May 2037 --> Jan 2030

P3, N=900, Recruiting, Genmab | Trial primary completion date: Jan 2025 --> Aug 2026

P1/2, N=49, Active, not recruiting, Genmab | Phase classification: P1 --> P1/2

P1/2, N=38, Not yet recruiting, Yazeed Sawalha

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.

P2, N=39, Recruiting, Australasian Leukaemia and Lymphoma Group | Not yet recruiting --> Recruiting

P2, N=35, Not yet recruiting, Beth Israel Deaconess Medical Center

P2, N=20, Not yet recruiting, Gottfried von Keudell, MD PhD

P3, N=360, Not yet recruiting, Genmab

P1/2, N=102, Active, not recruiting, Genmab | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

Single-cell immune profiling of tumor biopsies obtained following one cycle of therapy revealed substantial clonal expansion of cytotoxic CD4+ and CD8+ T-cells in patients achieving CR, and an expansion of follicular helper and regulatory CD4+ T-cells in patients whose disease progressed. These results identify distinct tumor-resident T-cell profiles associated with response or resistance to BsAb therapy.

P3, N=900, Recruiting, Genmab | Trial primary completion date: Jan 2027 --> Jan 2025

P2, N=31, Not yet recruiting, Abramson Cancer Center at Penn Medicine

P3, N=1080, Recruiting, Genmab | Trial primary completion date: Oct 2028 --> May 2037

P1, N=20, Not yet recruiting, Case Comprehensive Cancer Center

P2, N=180, Recruiting, Genmab | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Mar 2025 --> Jan 2026

P2, N=40, Not yet recruiting, Peter MacCallum Cancer Centre, Australia

In C1, adequate hydration and dexamethasone ( preferred steroid for mandatory CRS prophylaxis ) were recommended. Epcoritamab monotherapy showed early, deep responses in the largest R/R FL population treated with a T ​ cell − engaging therapy to date. CR and MRD negativity, including at C3D1, were associated with improved PFS. Safety was manageable in both cohorts, and CRS rate and severity were substantially reduced with C1 OPT, with few G2 and no G ≥ 3 events.

The C1 OPT cohort receivedrecommendations for adequate hydration and dexamethasone as the preferred steroid for CRS prophylaxis. MRD-negativity rate and kinetics, PK, longitudinal peripheral B​cell depletion, and T-cell counts were similarbetween groups and consistent with comparable clinical efficacy reported for the C1 OPT and 2-step SUDregimens. In contrast, IL-6 levels were substantially reduced for C1 OPT vs the 2-step SUD regimen.