On December 6, 2025 Kite, a Gilead Company (Nasdaq: GILD), reported Phase 1 data with encouraging efficacy and safety results for its two investigational bicistronic CAR T-cell therapies, KITE-753 and KITE-363, respectively, in patients with relapsed/refractory large B-cell lymphoma (R/R LBCL). The results of the analysis were shared in an oral presentation (Abstract #265) at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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Both KITE-753 and KITE-363 are bicistronic autologous CAR T-cell therapies. They are designed to target two antigens (CD19 and CD20) found on cancer cells and use two co-stimulatory domains (CD28 and 4-1BB) to help the immune system fight cancer more effectively. The KITE DuoCore construct – with two independent CARs working synergistically – may prevent relapse by reducing cancer cells escaping treatment and may help improve safety, making it possible to treat more patients outside of a hospital setting. Additionally, KITE-753 leverages a novel manufacturing process that preserves T-cell fitness. Combined, these attributes may contribute to better efficacy, lower toxicity, durable function, and faster delivery to patients.

"While CAR T-cell therapy has revolutionized treatment for many people with blood cancers, we urgently need options that not only improve upon the curative potential of existing cell therapies for evasive cancers but are also safer and available to a broader patient population," said Dr. Saurabh Dahiya, MD, FACP, the Stanford School of Medicine. "The encouraging response rates, durability and safety profile of KITE-753 and KITE-363 offer strong clinical evidence to support further development."

The open-label, multicenter, umbrella Phase 1 study enrolled 67 patients with R/R BCL. Thirty patients received KITE-753 and 37 received KITE-363.

Results for KITE-753 showed that at a median follow-up of 4.0 months overall and 2.9 months at dose level three (DL3; 0.2×106 CAR T cells/kg), 11 of 14 CAR-naïve patients (79%) receiving DL3 had a complete response, where the cancer completely disappeared. Bridging options in this Phase 1 study were limited to corticosteroid +/- radiation therapy, and all patients had measurable, active disease at the time of their infusion with KITE-753. No patients responded to these bridging therapy measures at DL3. Notably, KITE-753 demonstrated robust expansion despite a tenfold lower dose than DL3 of KITE-363 (2×106 CAR T cells/kg), which highlights the proliferative capacity of KITE-753. Across all dose levels, 14 of 20 CAR-naïve patients achieved a complete response.

Overall, KITE-753 showed an encouraging safety profile with no dose‑limiting toxicities. At DL3, no Grade ≥3 cytokine release syndrome (CRS) or immune effector cell‑associated neurotoxicity syndrome (ICANS) were observed; Grade ≥3 adverse events occurred in 95% of patients (primarily cytopenias), and serious Grade ≥3 adverse events occurred in 26% of patients. Across all dose levels, one Grade 3 CRS event (none Grade ≥4) and no Grade ≥3 ICANS events occurred.

"Kite is dedicated to pushing the boundaries of CAR T-cell therapy to deliver even greater impact and curative potential," said Dr. Gallia Levy, Senior Vice President, Global Head of Development at Kite. "By combining CD19/CD20 targeting with dual co‑stimulation, along with a manufacturing process resulting in a fit product, we aim to improve outcomes. Our goal is to bring CAR T to more patients, such as those with advanced disease who have exhausted other options, and to those who prefer to be treated in outpatient and in community oncology practice settings."

Meanwhile, results for KITE-363 revealed that at a median follow-up of 17.5 months, there was a durable benefit at the highest dose level (2×106 CAR T cells/kg) among CAR-naïve patients, with more than 70% of complete responders evaluable at 12 months remaining in remission. KITE-363 was generally well tolerated with no dose-limiting toxicities or severe side effects that required stopping the study. Grade ≥3 CRS occurred in one patient; Grade 3 ICANS occurred in two patients; no Grade ≥4 CRS/ICANS occurred.

About LBCL

Globally, large B-cell lymphoma (LBCL) is the most common type of non-Hodgkin lymphoma. In the United States, more than 18,000 people are diagnosed with LBCL each year. About 30–40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to initial treatment.

About the Study

Thirty patients received KITE-753 and 37 received KITE-363. The open-label, multicenter umbrella Phase 1 study enrolled eligible adults with R/R LBCL after ≥2 lines of therapy (patients with LBCL could have second-line primary refractory disease) in dose escalation (1A) and expansion (1B; LBCL only) cohorts. Following leukapheresis and lymphodepletion, patients received dose level (DL) 1, 2, or 3 of KITE-753 (3.0×104, 1.0×105, or 2.0×105 CAR T cells/kg, respectively) or KITE-363 (0.5×106, 1×106, or 2×106 CAR T cells/kg, respectively). Primary endpoints were incidence of dose-limiting toxicities (DLTs; Phase 1A) and investigator-assessed objective response rate (ORR; per Lugano; Phase 1B).

About KITE-753 and KITE-363

KITE-753 and KITE-363 are investigational, bicistronic autologous CAR T-cell therapies engineered to overcome tumor antigen heterogeneity and prevent relapse. The KITE DuoCore construct uniquely combines anti-CD19 and anti-CD20 targeting with dual co-stimulation (CD28 and 4-1BB). KITE-753 is an enhanced KITE DuoCore CAR T utilizing a novel manufacturing process, aiming to preserve T-cell fitness. Additionally, KITE-363 is being investigated for refractory autoimmune conditions.

(Press release, Gilead Sciences, DEC 6, 2025, View Source [SID1234661211])

On December 6, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage precision oncology company developing highly differentiated targeted agents to treat hematologic malignancies, reported clinical data for its lead compound tuspetinib (TUS) combined with standard dosing of venetoclax (VEN) and azacitidine (AZA) in a poster presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Orlando, FL. Updated data from patients in the TUSCANY trial across all three cohorts, 40 mg, 80 mg or 120 mg TUS dose in TUS+VEN+AZA, reveal promising clinical safety and antileukemic activity and support the use of TUS in combination with standard of care treatment across a broad range of AML populations, including those with adverse mutations regardless of FLT3 mutation status.

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Poster title: "TUSCANY study demonstrates safety and efficacy of tuspetinib plus standard of care venetoclax and azacitidine in patients with newly diagnosed AML ineligible for induction chemotherapy"

Key Findings and Messages:

In newly diagnosed AML patients, TUS+VEN+AZA shows promising safety, tolerability and resilient efficacy, including MRD-negative remissions across a broad mutational spectrum
High-quality clinical responses (CR/CRh):
90% across 40, 80 and 120 mg dose levels
100% at the higher 80 mg and 120 mg dose levels
Observed in FLT3-WT, FLT3-ITD, and NPM1c genetic subgroups
Observed in biallelic TP53/complex karyotype and RAS adverse genetic subgroups
Observed in AML with MDS-related mutations
MRD negativity: 78% by central flow cytometry in responding subjects
TUS targets VEN resistance mechanisms; inhibits kinase-driven abnormal signaling
Two subjects transitioned to stem cell transplantation and both returned for TUS maintenance
TUS+VEN+AZA triplet therapy was well tolerated with no dose-limiting toxicities (DLTs) across all evaluable TUS dose levels
No DLTs including no prolonged myelosuppression for subjects in remission in Cycle 1
No drug-related deaths, differentiation syndrome, QTc prolongation, or CPK elevation reported
8/10 evaluable subjects experienced red cell and platelet transfusion independence for > 8 weeks after their best response
Febrile neutropenia was reported in 2 subjects (16.7%), with 1 subject related to TUS
At the recently enrolled 160 mg dose level, preliminary findings show patients achieving early blast clearance with MRD-negativity and formal responses in the first few weeks of treatment (not included in poster data cut).

"Tuspetinib, as part of a triple drug therapy, continues to perform well, achieving 100% clinical response in the two higher doses we have evaluated to date," said Rafael Bejar, MD, PhD, Chief Medical Officer at Aptose. "We recently commenced treating patients at the highest dose level of 160 mg TUS and have already achieved early responses. With no dose-limiting toxicities and activity across diverse mutations, TUS+VEN+AZA targets AML’s greatest unmet needs and largest populations."

The ASH (Free ASH Whitepaper) poster presentation is available here.

About Tuspetinib

Aptose’s lead compound tuspetinib is a convenient once daily oral agent that potently targets SYK, mutated and wild type forms of FLT3, mutated KIT, JAK1/2, and RSK2 kinases, while avoiding many typical toxicity concerns observed with other agents. The ongoing TUSCANY triplet Phase 1/2 study is designed to test various doses and schedules of TUS in combination with standard dosing of azacitidine and venetoclax in newly diagnosed patients with AML who are ineligible to receive induction chemotherapy. Data from the first three dose cohorts demonstrate safety, CRs and minimal residual disease (MRD) negativity across patients with diverse mutations. The early data showed that 9 out of 10 patients responded to the TUS triplet therapy, with 100% complete remission (CR/CRh) achieved in the 80mg and 120mg cohorts. Notably, patients with difficult-to-treat mutations in TP53, RAS and FLT3 genes also achieved a 100% CR/CRh rate.

(Press release, Aptose Biosciences, DEC 6, 2025, View Source [SID1234661210])

On December 6, 2025 Star Therapeutics, a late clinical-stage biotechnology company discovering and developing best-in-class antibodies for bleeding disorders and other diseases, reported interim data from its ongoing Phase 1/2 multidose study of VGA039 in von Willebrand disease (VWD). The data are being presented in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, Florida. VGA039 is a first-in-class monoclonal antibody therapy that targets Protein S, with dual actions promoting platelet attachment and enhancing fibrin deposition to restore hemostasis.

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In the Phase 1/2 multidose study, treatment with VGA039 administered subcutaneously once monthly resulted in a substantial reduction in annual bleeding rate (ABR) across all types of VWD and all types of bleeds, including meaningful improvement in bleed control for patients switching from prior von Willebrand factor (VWF)-containing intravenous (IV) prophylaxis. The study population includes patients with Types 1, 2, and 3 VWD who have high disease burden, including patients with serious gastrointestinal (GI) and hemophilia-like joint and muscle bleeds.

"The data presented at ASH (Free ASH Whitepaper) indicate that VGA039 could be transformative for people living with VWD, a condition with more than 130,000 diagnosed patients in the U.S. alone," said Allison Wheeler, M.D., MSCI, Associate Professor of Pediatrics at the University of Washington. "VWD can have a significant impact on quality of life, with patients experiencing frequent and severe bleeds that can require hospitalization. Current treatment options remain limited, with VWF-containing prophylaxis requiring multiple IV infusions per week. Data from the multidose trial support a once monthly subcutaneous dosing regimen for VGA039, which could meaningfully alleviate the current treatment burden with the potential for even better bleed control over the standard of care."

Key highlights from the presentation include:

As of November 14, 2025, interim data from all 16 patients enrolled in the Phase 1/2 multidose study were available, including safety data on all 16 patients and efficacy data on all 8 patients who had completed treatment with VGA039.
VGA039 once monthly subcutaneous prophylaxis was safe and well tolerated.
VGA039 demonstrated substantial reductions in ABR across all patients, with all types of VWD and all types of bleeds (including serious GI and hemophilia-like joint and muscle bleeds).
Bleed reductions were 73%-87% for all the participants enrolled who have the same ABR as the population being recruited into the Phase 3 trial (ABR ≥ 12, no prior IV prophylaxis).
In patients switching from prior VWF-containing prophylaxis (IV infusions multiple times per week), bleed reductions were 75%-100%, indicating potential efficacy and dosing improvement over standard-of-care.
All participants to date who have completed the multidose study have transitioned to the open-label extension (OLE) study.
"This dataset is compelling, encompassing a diverse patient population across multiple VWD types, a full spectrum of bleed profiles, and individuals transitioning from prior prophylaxis regimens. VGA039’s ability to consistently reduce bleeding across these groups along with its favorable safety and tolerability profile indicate that VGA039 has the potential to improve outcomes for all patients with VWD," said Steven Pipe, M.D., Professor of Pediatrics and Pathology at the University of Michigan. "Importantly, patients who transitioned from IV prophylaxis multiple times per week to once monthly subcutaneous VGA039 experienced marked improvements in bleed control, highlighting the potential to establish a new standard of care for people living with VWD."

"These interim data provide further validation of VGA039 as a potential once monthly subcutaneous treatment for multiple bleeding disorders, starting with VWD. All patients to date have opted to continue treatment as part of our open-label extension study after finishing the multidose trial," said Gary Patou, M.D., Chief Medical Officer of Star Therapeutics. "These data, along with the recent initiation of our pivotal Phase 3 study, VIVID-6, continue to add to the momentum surrounding this program, bringing us another step closer to achieving our mission of creating life-changing therapies for patients with bleeding disorders."
About VGA039
VGA039 is a monoclonal antibody therapy with a novel mechanism of action that targets Protein S, with dual actions promoting platelet attachment and enhancing fibrin deposition to restore hemostasis. VGA039 has potential to be a universal hemostatic therapy that can treat numerous bleeding disorders, starting with von Willebrand disease (VWD). As a subcutaneously self-administered antibody therapy with a convenient once monthly dosing regimen, VGA039 has the potential to dramatically reduce treatment burden for patients. VGA039 has received Fast Track and orphan drug designations from the U.S. Food and Drug Administration (FDA). VGA039 has advanced into a Phase 3 study (NCT07115004), VIVID-6, a global single arm cross-over study designed to investigate the safety and efficacy of subcutaneous administration of VGA039 as prophylaxis for bleeding in patients with every type of VWD. For additional information on our VIVID trials of VGA039, including how to enroll, please visit the website here.

About von Willebrand disease
Von Willebrand disease (VWD) is the most common inherited bleeding disorder in which the blood does not clot properly, caused by absent or defective von Willebrand factor (VWF). VWD patients may experience excessive bleeding with varying severity and frequency, negatively impacting their daily lives. Current therapies for VWD prophylaxis include factor replacement therapies requiring multiple intravenous (IV) infusions every week. More than 130,000 people in the U.S. are diagnosed with VWD.

(Press release, Star Therapeutics, DEC 6, 2025, View Source [SID1234661209])

On December 6, 2025 Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, reported new data presented on its lead investigational allogeneic T-cell immunotherapy, Orca-T, at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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Orca-T with Reduced Intensity Conditioning

The new results of a single-center, open-label Phase 1 investigator-sponsored trial evaluating Orca-T in patients aged 60-75 (median 68 years) with a reduced intensity conditioning regimen (RIC) for the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN) showed a low incidence of both acute and chronic graft versus host disease (aGvHD, cGvHD) while maintaining a low rate of disease relapse.

"Many older patients with hematological malignancies are not eligible for myeloablative allogeneic stem cell transplant due to the significant toxicities associated with it. A conventional reduced intensity alloHSCT can be safer and more tolerable, but it may also reduce the curative potential," said Everett Meyer, M.D., Ph.D., hematologist and associate professor of medicine in Blood and Marrow Transplantation and Cellular Therapy at Stanford Health Care. "These early results suggest Orca-T following reduced intensity conditioning may preserve a meaningful graft-versus-leukemia effect while achieving low rates of toxicities, including acute and chronic GvHD. While additional research is needed, these findings support Orca-T as a potentially feasible option for older adults with blood cancer."

Highlighted in an oral session, patients (n=46) with 8/8 matched donors were conditioned with fludarabine/melphalan/total body irradiation (TBI) (n=11) or fludarabine/thiotepa/TBI (n=12). Conditioning was further reduced where 23 patients were enrolled in a cohort eligible for outpatient treatment. Also included in the analyses was a cohort of patients (n=7) with 7/8 matched donors receiving fludarabine/thiotepa/TBI.

All patients (n=53) had successful neutrophil engraftment at a median of 15 days (range 9-39). At one year, there was no aGvHD grade 3-4 observed, and the rate of aGvHD grade 2 was 12.3% (95% CI, 5-23%). The rate of moderate-to-severe cGvHD was 9.6% (95% CI, 3-21%). At one year, relapse-free survival (RFS) and graft versus host disease relapse-free survival (GRFS) were 82% (95% CI, 72-94%) and 72% (95% CI, 60-87%), respectively. The overall survival (OS) was 88% (95% CI, 79-98%) and non-relapse mortality (NRM) was 10% (95% CI, 4-20%). The outpatient-eligible cohort experienced NRM of 0%, RFS of 80% (95% CI, 65-100%) and OS of 95% (95% CI, 87-100%).

"We are energized by these new data, which reinforce our belief that Orca-T has the potential to expand curative treatment options to many more people living with serious blood cancers, including those who may not be eligible for a myeloablative transplant today, and even patients treated in the outpatient setting," said Nate Fernhoff, Ph.D., co-founder and chief executive officer at Orca Bio. "Our Serene-T Phase 2 study evaluating Orca-T with RIC recently opened for enrollment and is the next step towards understanding if Orca-T may provide a path to treatment for more patients in need of therapeutic options."

New Analyses from the Precision-T Phase 3 Study

Retrospective Comparison of Orca-T versus PTCy-Based GvHD Prophylaxis

An observational analysis compared a dataset derived from patients who received Orca-T in the Precision-T Phase 3 study (n=45) to a historical PTCy patient cohort (n=475) derived from the Center for International Blood and Marrow Transplant Research (CIBMTR).

At one year, OS was 94% with Orca-T compared to 81% with PTCy. RFS was 86% and 70% for Orca-T and PTCy, respectively. There was 0% NRM with Orca-T and 9.7% with PTCy, which achieved statistical significance. There was 13.8% relapse in the Orca-T cohort and 21% in the PTCy cohort. The rate of cGvHD was 14.7% with Orca-T versus 8.2% with PTCy. Of note, the OS in patients over the age of 50 was 100% with Orca-T compared to 75% with PTCy.

These outcomes were achieved using only single-agent tacrolimus for pharmacological GvHD prophylaxis for Orca-T recipients, in contrast to the triple-agent regimen used with PTCy, implicating the potential role of immune reconstitution in both disease control and mitigating posttransplant complications.

Orca-T Improved GvHD-free Survival Across Patient Demographics

In subset analyses from the Precision-T Phase 3 study comparing Orca-T to a conventional alloHSCT plus tacrolimus and methotrexate (Tac/MTX), Orca-T demonstrated improved clinical outcomes overall and across subgroups with varied demographic and clinical features. For all patients, the rate of survival free from cGvHD (cGFS) was 78% and 38% for Orca-T and Tac/MTX, respectively. For patients over the age of 50, the rate of cGFS was 74% and 35% for Orca-T and Tac/MTX, respectively. For all patients, the rate of GRFS was 63% and 31% for Orca-T and Tac/MTX respectively, and 59% and 23% for patients over the age of 50 with Orca-T and Tac/MTX, respectively.

Notably, OS and NRM were similar for patients aged 51-65 as in the entire safety population. For patients over the age of 50 at one year, OS was 94% (77%, 98%) for Orca-T patients (n=31) versus 80% (61%, 91%) for Tac/MTX patients (n=32) (HR=0.48 [0.12, 1.89]). Rates of NRM were 6.5% (1.1%, 19%) with Orca-T vs 16% with Tac/MTX (5.7%, 31%) (HR=0.49 [0.11, 2.06]). Together, these data suggest that the results of Orca-T extend to older patients and those with high-risk disease.

Health-Related Quality of Life: Patient Reported Outcomes

An exploratory endpoint from the Precision-T Phase 3 study evaluating health-related quality of life (HRQoL) and hospitalization patterns showed that Orca-T delivered marked improvements over conventional alloHSCT. Patients receiving Orca-T experienced faster recovery to, and higher improvement above, baseline HRQoL, fewer ICU stays, lower likelihood of rehospitalization and higher rehospitalization-free survival, suggesting better early post-treatment recovery and a lower burden of GvHD symptoms.

FACT-BMT total scores were consistently higher for Orca-T recipients across all time points, with Orca-T recipients exceeding baseline scores across physical well-being, functional well-being and transplant-specific subscales by day 100, while the alloHSCT arm did not surpass baseline until day 365. By day 365, Orca-T scores across these domains were higher by a magnitude of two or more compared to the control arm.

Rehospitalizations due to adverse events occurred less frequently among Orca-T recipients (27.3% [24] vs. 45.7% [43]), with fewer total hospitalization days per patient (30.6 vs. 40.8). Rehospitalization-free survival at 18 months was also significantly improved with Orca-T, reaching 66.4% (95% CI: 54.0, 76.2) compared to 33.8% (95% CI: 18.5, 49.9) for conventional alloHSCT (p=0.0096; HR 0.53 [0.32, 0.86]).

"The additional analyses from our Phase 3 study further highlight Orca-T’s potential superiority across critical measures, from lower rehospitalization rates to improved outcomes in older patients," said Scott McClellan, M.D., chief medical officer at Orca Bio. "These results continue to strengthen our conviction that Orca-T has the potential to transform the transplant experience and meaningfully raise the standard of care for patients and providers."

The safety and efficacy of Orca-T have not been determined by any regulatory authority. Orca-T is currently being evaluated under Priority Review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

About Precision-T
Precision-T (NCT05316701) is a randomized, open-label multi-center study that evaluated the safety, efficacy and tolerability of Orca Bio’s lead investigational allogeneic T-cell immunotherapy, Orca-T, compared to conventional allogeneic hematopoietic stem cell transplant (alloHSCT). Orca Bio received guidance from the U.S. Food and Drug Administration on the design of Precision-T, which evaluated Orca-T in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), high-risk myelodysplastic syndrome (MDS) and mixed-phenotype acute leukemia (MPAL). There are 19 leading treatment centers participating in the trial, which enrolled 187 patients across the U.S.

About Orca-T
Orca-T is an investigational allogeneic T-cell immunotherapy under evaluation for the treatment of multiple hematologic malignancies including acute leukemias and myelodysplastic syndromes. Orca-T is composed of highly purified regulatory T-cells, hematopoietic stem cells and conventional T-cells derived from either related or unrelated matched donors. Orca-T has received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug Designation for the prevention of graft versus host disease or death in patients eligible for hematopoietic stem cell transplant from the U.S. Food and Drug Administration (FDA). The Biologics License Application (BLA) for Orca-T is currently under Priority Review with the FDA with a Prescription Drug User Fee Act (PDUFA) target action date of April 6, 2026.

(Press release, Orca Bio, DEC 6, 2025, View Source;utm_medium=rss&utm_campaign=orca-bio-to-present-new-clinical-data-on-its-high-precision-cell-therapies-at-the-67th-american-society-of-hematology-annual-meeting-2 [SID1234661205])

On December 6, 2025 Genmab A/S (Nasdaq: GMAB) reported updated results from two ongoing clinical trials evaluating the efficacy and safety of epcoritamab-bysp, a T-cell engaging antibody administered subcutaneously, as a monotherapy and in combination with other standard of care treatments in adult patients with diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Results from two arms of the EPCORE NHL-2 trial, evaluating first-line, fixed-treatment duration epcoritamab in combination with chemotherapies, demonstrated overall response rates (ORR) of 93% (Arm 8) and 98% (Arm 1) in patients with newly-diagnosed DLBCL, while a third arm (Arm 3) demonstrated a three-year overall survival (OS) rate of 96% in patients with FL following first-line combination treatment.

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In EPCORE DLBCL-3, the ORR was 73% in elderly patients with DLBCL treated with first-line, fixed-duration epcoritamab monotherapy who were unable to receive standard anthracycline-based chemotherapy. The study also showed that 54% of patients were progression free and 65% were alive at one year. The results from both studies were presented today in two oral presentations (abstracts 63 and 64) and two poster presentations (abstracts 1955 and 5357) at the 67th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), in Orlando, Florida.

EPCORE NHL-2, Arm 8 Results
Two-year follow up from Arm 8 of the EPCORE NHL-2 trial (abstract 64) showed fixed-duration epcoritamab plus rituximab plus dose-attenuated cyclophosphamide, doxorubicin, vincristine, and prednisone (R-mini-CHOP) demonstrated an ORR of 93% and complete response (CR) rate of 86% in elderly patients with newly diagnosed DLBCL ineligible for full-dose R-CHOP due to age or comorbidities (n=28). Responses were maintained at two years for an estimated 79% of all responders. Additionally, 20 out of 22 patients who completed the eight cycles of treatment had a CR at the end of treatment and 90% of them remained in CR nearly two years later. Minimal residual disease (MRD) negativity was reported in 20 out of 21 evaluable patients, including clinically relevant sub-groups; this was achieved in 16 patients by the start of cycle 3, and 12 maintained this status through the start of cycle 6.

Treatment-emergent adverse events (TEAEs) were consistent with previous studies evaluating epcoritamab and included Grade ≥3 infection in 32% (n=9) of patients, occurring within the first 6 cycles of treatment in the majority (7/9) of these patients. TEAEs led to epcoritamab discontinuation in 11% (n=3) of patients, including Grade 2 rhinitis, Grade 2 cytokine release syndrome (CRS), and Grade 5 confusional state and cytomegalovirus infection reactivation in a 90-year-old patient with a recent acute cerebrovascular accident.

"Despite an older population of newly diagnosed diffuse large B-cell lymphoma, the outcomes observed in Arm 8 of the EPCORE NHL-2 evaluating fixed-duration epcoritamab plus R-mini-CHOP are encouraging," said Chan Cheah, M.D., Sir Charles Gairdner Hospital and the University of Western Australia, Nedlands, Australia. "These results, along with those from other arms of the trial, support the potential for combinations of epcoritamab with standard of care treatment across a range of disease settings and patient populations."

EPCORE NHL-2; Arm 1 Results
In Arm 1 (abstract 1955), treatment with fixed-duration epcoritamab plus R-CHOP resulted in durable remissions lasting more than three years in most patients with newly diagnosed DLBCL and high International Prognostic Index (IPI) scores, an indicator of poor prognosis (n=47). After a median follow up of 44.2 months (95% CI, 38.9-44.4), the ORR was 98% and the CR rate was 85%. An estimated 74% of CRs were ongoing at three years. High CR rates were observed regardless of IPI score (IPI 3, 86% vs IPI 4-5, 83%). At three years, an estimated 69% of patients remained progression free and 83% were alive; survival outcomes were consistent regardless of IPI score (3 vs 4–5). Efficacy outcomes were also similar across subgroups based on age (≤60 vs >60 years), tumor size (<10 vs ≥10 cm), or cell of origin (germinal center B cell [GCB] vs non-GCB). By cycle 3, 86% of MRD evaluable patients were MRD negative and the reduction of circulating tumor DNA (ctDNA) levels was sustained through post-treatment follow-up in most patients with CR.

Serious and Grade ≥3 infections primarily occurred in the first six months of treatment, then rates decreased. Safety was consistent with prior reports. No new serious infections were reported in the post-treatment period. No new Grade 5 adverse events (AEs) were reported.

EPCORE NHL-2; Arm 3 Results
Data from Arm 3 (abstract 5357) showed that treatment with fixed-duration epcoritamab plus bendamustine and rituximab (BR) for the first-line treatment of FL resulted in deep and durable responses at a median follow-up of 41.3 months. Three-year estimates for duration of response (DOR), duration of CR (DOCR), progression-free survival (PFS) and OS were 87%, 87%, 83% and 96%, respectively. PFS was consistently high overall and in both low- and high-risk subgroups. These results underscore the potential for long-term efficacy of this first-line treatment combination in FL.

No new safety signals were reported after the data cutoff/additional 11 months of follow up. Grade ≥3 TEAEs and serious TEAEs, including neutropenia and infection, primarily occurred in the first 24 weeks of treatment, coinciding with the epcoritamab plus BR treatment period, and rates improved over time during the epcoritamab monotherapy treatment period. Since the prior data cutoff, three patients experienced new COVID-19 infection events (Grade 1-2). There was a sustained reduction in peripheral CD4+ T cells, whereas peripheral CD8+ T cells expanded after the first full dose, resulting in a reduced CD4:CD8 ratio.

"The ongoing epcoritamab development program continues to generate positive data supporting its potential as a core therapy alone and in combination across a range of B-cell malignancies, both as an initial treatment and in later lines of therapy," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "We look forward to progressing our research as we seek to advance treatment in these areas of critical need."

EPCORE DLBCL-3 Trial Results
Separately, new results from the ongoing Phase 2 EPCORE DLBCL-3 trial (abstract 63), for fixed-duration epcoritamab monotherapy in newly diagnosed elderly patients with DLBCL and comorbidities, were also presented.

An ORR of 73% was observed (n=60 response evaluable patients), and 62% of patients achieved a CR. Median time to response was 1.5 months, and median time to CR was 2.1 months; eight patients with a partial response or stable disease at first assessment achieved a CR at subsequent assessments. Median duration of response (mDOR) and median duration of CR (mDOCR) were not reached (NR). An estimated 70% of all responses and 78% of CRs were ongoing at one year. In the overall population (N=66), median PFS was 13.0 months (95% CI, 5.4–NR) and median OS was NR (95% CI, 13.0–NR). An estimated 54% of patients were progression free, and 65% were alive at one year. Additionally, MRD negativity in responders was also reached early and was maintained, with most becoming MRD negative by the third treatment cycle and sustained through post-treatment follow-up.

Safety was consistent with previous reports of epcoritamab monotherapy in this population. TEAEs occurred in 94% of patients, with CRS (71%), diarrhea (23%), and fatigue (23%) being most frequent (≥20%). CRS events were primarily low Grade (Grade 1: 38%; Grade 2: 29%; Grade 3: 5%), with most (92%) occurring in cycle 1; 98% of cases resolved by data cutoff. ICANS occurred in 18% of patients (Grade 1: 8%; Grade 2: 8%; Grade 3: 3%); 11/12 cases resolved by data cutoff. Neutropenia was reported in 16% of patients, 68% of patients had an infection of any Grade, and 23% had a Grade ≥3 infection. Two additional Grade 5 TEAEs (pneumonia, death) occurred since the previous disclosure.

"Elderly patients who are living with diffuse large B-cell lymphoma, particularly those with comorbidities, often are not able to tolerate standard treatment, creating a tremendous need for effective chemotherapy-free options," said Umberto Vitolo, M.D.,Candiolo Cancer Institute in Turin, Italy. "The study showed that treatment with fixed-duration epcoritamab as a monotherapy demonstrated encouraging results in this population that typically has poor outcomes."

The safety and efficacy of epcoritamab have not been established for these investigational uses.

About Diffuse Large B-Cell Lymphoma (DLBCL)
DLBCL is the most common type of non-Hodgkin lymphoma (NHL) worldwide, accounting for approximately 25-30 percent of all NHL cases.i In the U.S., there are approximately 25,000 new cases of DLBCL diagnosed each year.ii DLBCL can arise in lymph nodes as well as in organs outside of the lymphatic system, occurs more commonly in the elderly and is slightly more prevalent in men.iii,iv DLBCL is a fast-growing type of NHL, a cancer that develops in the lymphatic system and affects B-cell lymphocytes, a type of white blood cell. For many people living with DLBCL, their cancer either relapses, which means it may return after treatment, or become refractory, meaning it does not respond to treatment. Although new therapies have become available, treatment management can remain a challenge.

About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes and is the second most common form of NHL accounting for 20-30 percent of all cases.v About 15,000 people develop FL each year in the U.S.vi and it is considered incurable with current standard of care therapies.vii Patients often relapse and, with each relapse the remission and time to next treatment is shorter.viii Over time, transformation to diffuse large B-cell lymphoma (DLBCL), an aggressive form of NHL associated with poor survival outcomes, can occur in more than 25 percent of FL patients.ix

About the EPCORE NHL-2 Trial
EPCORE NHL-2 is a Phase 1b/2 open-label interventional trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab as a monotherapy and in combination with other standard of care agents in patients with B-cell non-Hodgkin lymphoma (B-NHL). The trial consists of two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). The primary objective of Part 1 is safety, and the primary goal of Part 2 is preliminary efficacy. The primary endpoint was overall response rate (ORR) based on best overall response per Lugano criteria. MRD negativity was assessed as a secondary endpoint.

More information on this trial can be found at View Source (NCT: 04663347).

About the EPCORE DLBCL-3 Trial
EPCORE DLBCL-3 is an open-label, randomized, global, Phase 2 trial to evaluate the efficacy and safety of epcoritamab as monotherapy or in combination with lenalidomide as first-line therapy for anthracycline-ineligible subjects with diffuse large B-cell lymphoma (DLBCL). This is a 2-stage trial. In Stage 1, eligible patients will be randomized to either epcoritamab monotherapy or epcoritamab plus lenalidomide. In Stage 2, additional patients may be enrolled at the treatment regimen selected for expansion. Each treatment cycle is 28 days. Patients will receive a maximum of 12 cycles (up to 1 year) of treatment. The primary objective is to evaluate the clinical efficacy of epcoritamab monotherapy or epcoritamab and lenalidomide. The primary endpoint is to achieve a complete response rate determined by Lugano criteria. Additional secondary endpoints include overall response rate, duration of response, duration of complete response, rate of minimal residual disease negativity, progression-free survival and overall survival.

More information on this trial can be found at View Source (NCT:05660967).

About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology and administered subcutaneously. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.x

Epcoritamab (approved under the brand name EPKINLY in the U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Where approved, epcoritamab is a readily accessible therapy. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational R/R FL indication and additional approvals for the R/R DLBCL indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes four ongoing Phase 3, open-label, randomized trials, among them a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with R2 compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744), and a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

(Press release, Genmab, DEC 6, 2025, View Source [SID1234661200])