Epkinly (epcoritamab-bysp)

Historically, B and T cell (B-T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab or ofatumumab...In the treatment of cancer, chimeric antigen receptor (CAR) T cell therapy and T cell engagers (TCE) that recruit T cells to induce B cell cytotoxicity have delivered promising results for anti-CD19 CAR T cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab or epcoritamab. Limited evidence suggests that anti-CD19 CAR T cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. Therefore, here, we discuss the potential mechanistic advantages of novel therapies that rely on T cells as effector cells to disrupt B-T cell collaboration toward overcoming rituximab-resistant AID.

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

Whilst there are many promising novel drugs in early clinical development for rrFL, understanding the relative efficacy and safety of these agents, and their place in modern treatment pathways, is limited by a lack of randomised trials and dearth of published outcomes for standard regimens to act as historic controls. Therefore, the aim of REFRACT is to provide an efficient platform to evaluate novel agents against standard therapies for rrFL. The adaptive Bayesian power prior methodology design will minimise patient numbers and accelerate trial delivery.

P3, N=900, Recruiting, AbbVie | Trial completion date: May 2030 --> Dec 2029

P1/2, N=666, Active, not recruiting, Genmab | Recruiting --> Active, not recruiting | Trial completion date: Apr 2029 --> Jan 2029

P3, N=900, Recruiting, AbbVie | Trial completion date: Sep 2037 --> May 2037

P1, N=49, Active, not recruiting, AbbVie | Phase classification: P1b/2 --> P1 | Trial completion date: Jan 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Dec 2024

Based on the EPCORE-NHL-1 study, one of the first pivotal studies to report MRD in pts with R/R FL, epcoritamab drives rapid, deep, and sustained responses as supported by MRD assessment by both PBMC and ctDNA. MRD results correlate with clinical outcome, and achieving MRD negativity is associated with longer PFS. PFS was similar among all pts who achieved MRD negativity, including those with high-risk disease.

P2, N=39, Not yet recruiting, Australasian Leukaemia and Lymphoma Group

P2, N=120, Not yet recruiting, Academic and Community Cancer Research United

P3, N=900, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P3, N=900, Not yet recruiting, AbbVie | Initiation date: Mar 2026 --> Jan 2024

P2, N=27, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

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

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

P3, N=900, Not yet recruiting, AbbVie

P1/2, N=662, Recruiting, Genmab | Phase classification: P1b/2 --> P1/2

P1/2, N=184, Recruiting, Genmab

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.

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.

Eligible treatments included CAR T cell therapies (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel), T cell engagers (mosunetuzumab, glofitamab, epcoritamab, odronextamab), phosphatidylinositol 3-kinase (PI3K) inhibitors (copanlisib, duvelisib, idelalisib), HSCT, yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, and conventional therapies (immunochemotherapies, single- or multiagent chemo- or immunotherapies, and alkylating agents). This SLR demonstrated an evolving FL treatment landscape, with new agents such as CAR T cell therapies and T cell engagers exhibiting potential for improving effectiveness of treatment for patients in 3L+, 4L+, and 2L+ POD24 populations.

P3, N=500, Recruiting, AbbVie | Trial completion date: Feb 2031 --> Jun 2030

Patients (pts) with previously untreated (1L) diffuse large B-cell lymphoma (DLBCL) typically receive rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); however, approximately 40% are refractory or relapse. Table 1. 55 Myeloproliferative neoplasms I

Here we present pooled analyses of epcoritamab with rituximab + lenalidomide (R2 ) from cohorts 2a and 2b of the ongoing phase 1/2 EPCORE™ NHL-2 trial (NCT04663347). Encouraging responses were observed in high-risk pts, suggesting SC epcoritamab may abrogate negative effects of high-risk features. A separate POD24 cohort is planned, and the phase 3 EPCORE FL-1 trial of epcoritamab + R2 (NCT05409066) is ongoing.

P1/2, N=184, Recruiting, Genmab | Phase classification: P1b/2 --> P1/2

P1, N=15, Recruiting, AbbVie | Phase classification: P1b --> P1

P2, N=394, Recruiting, AbbVie | Phase classification: P1b/2 --> P2

Cytokine release syndrome occurrence was predictable; events were primarily low grade (grade 1-2), all resolved, and none led to treatment discontinuation. These encouraging results are consistent with previous findings and support the ongoing clinical evaluation of epcoritamab for the treatment of R/R DLBCL, including in earlier treatment lines.

Glofitamab results in per-patient cost savings compared with epcoritamab at every cumulative administration cycle, particularly in the first few cycles when epcoritamab has more frequent dosing per cycle than glofitamab. Furthermore, glofitamab has lower total costs across all time horizons examined in this study (1-year, 5-year, 10-year, and lifetime). The lower total costs with glofitamab can be attributed to 1) lower annual drug acquisition costs, 2) fixed-duration treatment with a maximum of 12 cycles, and 3) less frequent dosing in earlier cycles.

Bispecific antibodies (BiAb), such as FDA-approved Epcoritamab and Glofitamab, had a complete response (CR) rate of 39% for DLBCL. PTT in lymphoma is understudied and can effectively activate an anti-lymphoma response. PTT resulted in a marked reduction in PD1 expression on all T cells and activated several myeloid immune cells. We found that PTT combined with aPD1 therapy or BiAbs had improved tumor suppression in a lymphoma model.

Epcoritamab combined with lenalidomide showed promising antitumor activity with a tolerable safety profile in patients with R/R DLBCL.

Background: Epcoritamab SC, a CD3xCD20 T-cell–engaging bispecific antibody, has recently been approved by the US FDA for the treatment of adults with relapsed/refractory (R/R) diffuse large B‑cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma after ≥2 lines of systemic therapy...To further mitigate CRS, C1 of the optimization cohort included mandatory administration of dexamethasone 15 mg as premedication on D1, D8, D15, and D22 and as prophylaxis on D2–4, D9–11, D16–18, and D23–25, and diphenhydramine and acetaminophen as premedication on D1, D8, D15, and D22 with each dose...All CRS events were G1; 1 patient was treated with anticytokine therapy (tocilizumab); there were no treatment discontinuations due to CRS... Encouraging preliminary data from this DLBCL CRS optimization cohort, which incorporates prophylactic dexamethasone and hydration of patients during cycle 1, indicate that this approach is effective in decreasing rates and severity of CRS. Data with additional patients and follow-up will be presented.

Common prior therapies included anthracyclines (77%), lenalidomide (31%), and autologous stem cell transplant (19%). Single-agent epcoritamab SC resulted in deep and durable responses with high ORR and CR rates in hard-to-treat, high-risk pts with R/R FL. Responses were consistent across subgroups. A correlation between MRD negativity and PFS was observed.

P2, N=27, Not yet recruiting, City of Hope Medical Center

P1b/2, N=49, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

These data with longer follow-up reaffirm that single-agent SC epcor induces durable CRs with a manageable safety profile in challenging-to-treat pts with R/R DLBCL. Data support ongoing phase 3 studies evaluating epcor in various combinations and tx settings.

P2, N=40, Not yet recruiting, M.D. Anderson Cancer Center

Clinical development of epcoritamab as monotherapy and in combination with standard of care agents for the treatment of mature B-NHLs is ongoing globally. This article summarizes the milestones in the development of epcoritamab leading to this first approval for R/R DLBCL.

P1/2, N=46, Terminated, Genmab | N=182 --> 46 | Trial completion date: Sep 2025 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Sep 2023 --> Nov 2022; Due to strategic evaluation of GEN3009 within context of Genmab's portfolio, decision not based on any safety or regulatory concerns.

In patients with newly diagnosed DLBCL, standard treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has a 5-year progression-free survival (PFS) rate of 67.0%, 58.4%, and 45.8% for International Prognostic Index (IPI) 2, 3, and 4–5. Safety endpoints: include incidence/severity of treatment-emergent adverse events (AEs), serious AEs, and AEs of special interest (CRS, immune cell–associated neurotoxicity syndrome, and clinical tumor lysis syndrome). Enrollment opened January 2023.

The patient was enrolled in a clinical trial comparing brentuximab, vedotin, or placebo in combination with lenalidomide and rituximab (ECHELON-3)...Currently, the patient is waiting for a seventh line of treatment with epcoritamab. Treatment of advanced-stage DLBCL with curative intent using rituximab-based chemotherapy is associated with long- term survival in more than two-thirds of patients. We described a case of double hit GBC DLBCL refractory to chemoimmunotherapy and CAR-T therapies.