Epkinly (epcoritamab-bysp)

Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) resulted in complete molecular remission (CMR). The antibody test for JCV is recommended for patients with multiple sclerosis for an earlier diagnosis, which is not common in other diseases. We should be aware of PML through innovative therapy.

P2, N=200, Not yet recruiting, Peking University Shenzhen Hospital

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

With a 3-year follow-up, epcoritamab continued to show deep and durable responses, with more than half of complete responders remaining in remission at 3 years: median duration of CR, 36.1 mo. Sustained MRD negativity was observed. Long-term safety was consistent with prior reports.

With over 3 years of follow-up, single-agent epcoritamab demonstrated deep and durable responses and manageable side effects in CAR T–naive pts with R/R LBCL, as demonstrated by this subgroup analysis. Results were consistent with those seen in the overall EPCORE NHL-1 LBCL population, considering differences in baseline characteristics, and show that epcoritamab can be administered safely and effectively before or after CAR T for the treatment of R/R LBCL.

For patients (pts) with R/R FL, rituximab + lenalidomide (R2) is an approved and widely accepted regimen based on results from the AUGMENT trial (overall response rate [ORR], 78%; complete response [CR] rate, 34%; estimated 2-y progression-free survival [PFS], 58%). With more than 2 y of follow-up, fixed-duration epcoritamab + R2 continued to show deep and durable responses (CR rate, 87%; estimated 24-mo DOCR, 75%) in pts with R/R FL, irrespective of high-risk features. Considering limitations of cross-trial comparisons, these results (estimated 2-y PFS, 70%) compare favorably with those reported for R2 alone in the AUGMENT trial (estimated 2-y PFS, 58%). The depth of responses was underscored by MRD negativity in 88% of evaluable pts.

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