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])

On December 6, 2025 Disc Medicine, Inc. (NASDAQ:IRON), a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of novel treatments for patients suffering from serious hematologic diseases, reported positive initial data from the RALLY-MF Phase 2 trial of DISC-0974 in anemia of MF at the ASH (Free ASH Whitepaper) Annual Meeting in Orlando, FL. The data demonstrated that treatment with DISC-0974 resulted in substantial reductions in hepcidin and increases in iron levels translating to positive impact on clinically meaningful measures of anemia across a broad range of patient types.

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"We are excited that we continue to see robust hematologic responses to DISC-0974 regardless of background JAK inhibitor therapy," said John Quisel, J.D., Ph.D., President and Chief Executive Officer of Disc Medicine. "It is also encouraging to see these hematologic improvements translating into reduced transfusion burden and fatigue. We look forward to advancing this program with the goal of addressing a significant unmet need as anemia is one of the key manifestations of MF and there is currently no therapy approved to treat anemia in this population."

This ongoing Phase 2 open-label study had enrolled 47 adult patients with MF and anemia as of the data cutoff date of October 16, including 34 patients with sufficient follow up to be included in the responder analysis (non-transfusion dependent receiving no transfusions (nTD, n=24), transfusion dependent with low transfusion burden (TD Low, n=7) and transfusion dependent with high transfusion burden (TD High, n=3)). The trial was comprised of both patients receiving concomitant JAK inhibitor therapy (n=18) and not receiving JAK inhibitor therapy (n=16). DISC-0974 was administered subcutaneously at 50 mg every 4 weeks for up to 6 treatments. Initial results demonstrated:

Consistent, substantial decreases in hepcidin reaching >75% reduction from baseline and corresponding increases in serum iron
63% of baseline nTD patients achieved a hemoglobin increase of ≥1 g/dL for ≥12 weeks (overall response) and 50% had an increase of ≥1.5 g/dL for ≥12 weeks (major response)
71% of TD Low patients achieved transfusion independence (TI, major response) over a 16-week period
67% of TD High patients with at least 85 days on study achieved a ≥50% reduction in transfusion requirement (overall response)
Initial data for additional n=3 TD High patients trending towards major response of TI >12 weeks
50% of patients receiving concomitant JAK inhibitor therapy achieved a major hematologic response
Dosing with DISC-0974 was associated with improvements in FACIT-Fatigue scores in nTD and TD Low participants
DISC-0974 was generally well-tolerated. Diarrhea and urinary tract infections, neither considered serious, were the only adverse events (AE) that were considered related to DISC-0974 and reported in two or more subjects. The majority of AEs were not considered related to DISC-0974.
Additional data to be shared in H2 2026
Disc also shared a poster overviewing the trial design for the ongoing Phase 2 study of the anti-TMPRSS6 antibody DISC-3405 in polycythemia vera requiring frequent phlebotomy.

Management will host a call during the ASH (Free ASH Whitepaper) meeting to review highlights of the presented data and plans for next steps in development on Sunday, December 7 at 7:30am EST. Please register for the event on the Events and Presentations page of Disc’s website (View Source).

(Press release, Disc Medicine, DEC 6, 2025, View Sourcenews-releases/news-release-details/disc-medicine-presents-positive-initial-data-rally-mf-phase-2 [SID1234661198])

On December 6, 2025 Cogent Biosciences, Inc. (NASDAQ: COGT) reported complete results from the registration-directed Part 2 of the SUMMIT clinical trial of bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM). As previously reported, bezuclastinib demonstrated clinically meaningful and highly statistically significant improvements across the primary and all key secondary endpoints. New results further highlight the benefit of bezuclastinib on patient-reported symptoms and objective measures of mast cell burden and demonstrate significant correlation between improvement in disease pathology and patient-reported symptom severity.

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"We are excited to present additional data from the SUMMIT trial that support our conviction that bezuclastinib will be the best-in-class treatment option for patients with nonadvanced systemic mastocytosis," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "We remain on track to submit our first New Drug Application for bezuclastinib in NonAdvSM with the FDA this month and are encouraged by the increased interest in our Expanded Access Program."

"Nonadvanced systemic mastocytosis patients currently have very limited treatment options, and the benefit bezuclastinib demonstrated in the SUMMIT trial across measures of disease pathology and symptomatic improvement is very exciting for this patient population," said Lindsay Rein, MD, Associate Professor of Medicine in the Division of Hematologic Malignancies and Cellular Therapy, Duke University. "The SUMMIT trial results match my clinical experience using bezuclastinib with NonAdvSM patients, delivering rapid and deep improvement in symptom control and objective measures of disease without tolerability challenges."

SUMMIT Trial Data

In the registration-directed Part 2 of the SUMMIT clinical trial, 118 patients received bezuclastinib once daily plus best supportive care (BSC) and 60 patients received placebo plus BSC. The study included adults with a NonAdvSM diagnosis confirmed by central pathology review, and moderate-to-severe symptom burden despite an optimized regimen of BSC.

Following completion of the 24-week treatment period, patients had the option to receive bezuclastinib in an open-label extension study. Baseline patient demographics were balanced between treatment arms and reflected significant disease burden. Disease symptoms were assessed using the Mastocytosis Symptom Severity Daily Diary (MS2D2).

Bezuclastinib delivered clinically meaningful and statistically significant symptomatic improvement

Outcome measure Bezuclastinib Placebo p-value
At 24 weeks of treatment (primary endpoint and key secondary endpoints)
Mean change TSS (%) -24.3 (-43%) -15.4 (-29%) p<0.001
Proportion of patients with ≥50% reduction in TSS 34.3% 18.1% p=0.01
Proportion of patients with ≥30% reduction in TSS 65.4% 38.6% p<0.001
For patients treated through 48 weeks (follow-up data cut off Nov 2025)
Mean change TSS (%) -32.0 (-54%) n/a n/a
Proportion of patients with ≥50% reduction in TSS 56.4% n/a n/a
Proportion of patients with ≥30% reduction in TSS 86.2% n/a n/a

Across several additional key secondary endpoints, bezuclastinib demonstrated rapid, deep and sustained improvement on objective disease markers of mast cell burden. At week 24, 87.4% of patients achieved ≥50% reduction in serum tryptase levels, 75.6% of patients demonstrated ≥50% reduction in bone marrow mast cells or clearance of aggregates and 85.7% of patients achieved ≥50% reduction in KIT D816V variant allele frequency or undetectable, each of which was statistically significant when compared to placebo. Additional pathobiology data from SUMMIT patients will be shared in an oral presentation on Monday, December 8th at ASH (Free ASH Whitepaper).

SUMMIT Subgroups

As part of the SUMMIT study, patients with Smoldering Systemic Mastocytosis (n=8 bezuclastinib arm, n=4 placebo arm) and patients who had previously been treated with avapritinib (n=11 bezuclastinib arm, n=3 placebo arm) were enrolled. Patients treated with bezuclastinib in these subgroups showed a mean change in TSS of -35.6 and -21.6, respectively. The response in objective measures of disease burden in these patients was consistent with results from the broader SUMMIT population, as were their related adverse events and overall tolerability.

Safety Data

As previously reported on July 7, 2025, the majority of treatment emergent adverse events (TEAEs) (98.3% in bezuclastinib arm vs. 88.3% in placebo arm) were of low grade. The most frequent TEAEs reported on bezuclastinib treatment were hair color change (69.5% bezuclastinib vs. 5.0% placebo), altered taste (23.7% bezuclastinib vs. 0% placebo), nausea (22.0% bezuclastinib vs. 13.3% placebo) and ALT/AST elevations (22.0% bezuclastinib vs. 6.6% placebo; ≥Gr 3, 5.9% vs. 0%). Serious AEs occurred in 4.2% of patients treated with bezuclastinib, compared to 5.0% of patients treated with placebo. Discontinuations due to treatment-related AEs occurred in 5.9% of patients treated with bezuclastinib, all due to ALT/AST elevations and all patients fully resolved. There were no hepatic AEs reported in any patient other than transient and manageable lab abnormalities.

SUMMIT Long Term Follow-up

Data from longer term follow-up in patients participating in the SUMMIT trial are expected to be presented at an upcoming scientific meeting in Q1 2026. Preliminary 48-week data will be shared during the investor call scheduled for Monday, December 8th.

(Press release, Cogent Biosciences, DEC 6, 2025, View Source [SID1234661197])

On December 6, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4") reported data from the non-pivotal dose-confirmation stage of the global randomized Phase 3 trial PRESERVE-003 (NCT05671510) for gotistobart (also known as BNT316 or ONC-392), a tumor microenvironment-selective regulatory T cell ("Treg") depletion candidate, targeting CTLA-4 in patients with metastatic squamous non-small cell lung cancer (sqNSCLC). Gotistobart demonstrated a clinically meaningful overall survival ("OS") benefit compared to standard-of-care chemotherapy and a manageable safety profile in sqNSCLC patients whose disease had progressed following anti-PD-(L)1 therapy and platinum-based chemotherapy. Data from the non-pivotal stage of the trial are being presented today in an oral presentation at the IASLC ASCO (Free ASCO Whitepaper) 2025 North America Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer in Chicago, Illinois, USA.

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"With a median survival of less than a year, advanced squamous NSCLC remains an aggressive and difficult-to-treat lung cancer1,2. Survival outcomes have improved in recent years due to advances in immunotherapy and combination regimens. However, patients who progress on anti-PD-(L)1 inhibitor treatment face a poor prognosis, leaving them only with the option of chemotherapy or palliative care," said Byoung Chul Cho, M.D., Ph.D., Lead Investigator and Professor at the Division of Medical Oncology, Yonsei Cancer Center, Seoul. "We are encouraged by the median overall survival still not being reached for patients treated with gotistobart at almost 15 months of follow-up, and we are excited to continue to investigate the candidate’s potential in the ongoing pivotal stage of the trial."

The analysis from the non-pivotal stage of the global Phase 3 trial included 45 metastatic sqNSCLC patients who received gotistobart as monotherapy, compared with 42 metastatic sqNSCLC patients who received chemotherapy (docetaxel) as second or later line of systemic therapy. At the data cut-off on August 8, 2025, 87 patients with sqNSCLC had been randomized to either gotistobart 6 mg/kg with two 10 mg/kg loading doses (N=45) or docetaxel 75 mg/m2 (N=42). The OS rate at 12 months was 63.1% for gotistobart compared to 30.3% for docetaxel. At a median follow-up of 14.5 months, patients in the gotistobart treatment arm had not yet reached the median OS, while the docetaxel treatment arm achieved a median OS of 10 months. The data showed that the gotistobart arm reduced the risk of death by 54% compared to the docetaxel treatment arm (HR=0.46, 95% CI: 0.25–0.84; nominal p-value 0.0102). The safety profile of gotistobart was consistent with previously established data and remained manageable. Grade ≥3 treatment-related adverse events ("AEs") were reported in 19/45 (42.2%) patients in the gotistobart treatment arm versus 20/41 (48.8%) patients in docetaxel treatment arm. The pivotal stage of the Phase 3 trial is ongoing in more than 160 sites globally.

"Gotistobart is designed to selectively deplete tumor-infiltrating regulatory T cells within the tumor microenvironment. The data presented today showed encouraging signals for our approach to translating our deep understanding of the immune system into meaningful survival benefits for patients with squamous NSCLC," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "With its unique mode of action, we are investigating gotistobart both as a monotherapy and in synergistic combinations with other modalities. Our goal is to deliver transformative treatment options that provide meaningful and durable benefits for patients."

"Gotistobart represents a step forward in our goal of offering a chemotherapy-free treatment option for patients with advanced squamous NSCLC, a population with limited therapeutic choices and a lack of actionable biomarkers to guide treatment," said Pan Zheng, M.D., Ph.D., Chief Medical Officer and Co-Founder at OncoC4. "The encouraging data presented today underscore the potential of gotistobart to address the unmet medical needs. We look forward to continuing to jointly explore the potential of the novel mechanism of action and advance clinical development for patients who have not benefited from currently approved immunotherapy."

About the PRESERVE-003 trial
PRESERVE-003 (NCT05671510) is a two-stage, open-label Phase 3 trial evaluating the efficacy and safety of gotistobart as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in sqNSCLC patients, who have progressed on PD-(L)1 inhibitors and platinum-based chemotherapy. The non-pivotal stage of the trial originally included all NSCLC patients. The ongoing pivotal stage is currently enrolling patients with sqNSCLC. During the ongoing pivotal stage, approximately 500 patients are planned to be enrolled at clinical sites in various countries and regions, including Australia, Belgium, Canada, China, Germany, Italy, the Netherlands, Spain, South Korea, Türkiye, the United Kingdom and the United States. The primary endpoint is overall survival. Secondary endpoints include overall response rate, progression-free survival and safety profile.

About gotistobart (BNT316/ONC-392)
Gotistobart (BNT316/ONC-392) is a tumor microenvironment-selective Treg depletion candidate developed jointly by BioNTech and OncoC4. As a pH-sensitive monoclonal antibody, gotistobart is designed to enable CTLA-4 protein recycling. After binding to the CTLA-4 receptor on the cell surface, the complex is internalized, and the pH change causes the antibody to unbind, allowing CTLA-4 to return to the surface to preserve the immune checkpoint function at peripheral organs and to enhance anti-tumor immunity in the tumor microenvironment3. Gotistobart is currently in late-stage clinical development as monotherapy and as a component of combination therapy in various cancer indications. Gotistobart has received Fast Track Designation from the U.S. Food and Drug Administration ("FDA") in 2022 for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy and Breakthrough Therapy Designation from China’s National Medical Products Administration ("NMPA") in 2025.

Multiple trials are ongoing, including a pivotal Phase 3 trial (PRESERVE-003; NCT05671510) in patients with metastatic squamous NSCLC, a Phase 2 trial (PRESERVE-004; NCT05446298) in patients with platinum-resistant ovarian cancer, a Phase 2 trial (PRESERVE-006; NCT05682443) in patients with metastatic castration-resistant prostate cancer, and a Phase 1/2 open-label dose escalation trial (PRESERVE-001; NCT04140526) in patients with advanced solid tumors. BioNTech also evaluates gotistobart in combination with its mRNA cancer immunotherapy candidate BNT116 in a signal seeking cohort of the ongoing Phase 1 trial (LuCa-MERIT-1; NCT05142189).

About NSCLC
Non-small cell lung cancer ("NSCLC") covers all epithelial lung cancers other than small cell lung cancer and includes squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung. It is the most common type of lung cancer, accounting for up to 85% of cases4, with risk factors ranging from smoking to asbestos exposure and pulmonary fibrosis5. Around 25% of all lung cancer cases are attributed to the subtype squamous cell carcinoma (SCC)6. With a 5-year relative survival rate of 15% and a median overall survival of 11 months in the United States (2000-2017), sqNSCLC is a devastating disease with limited treatment options7. Current standard-of-care includes surgery and radiotherapy in combination with chemotherapy8. Treatment options for second-line therapy after first-line immunotherapy and chemotherapy are limited to chemotherapy or palliative therapy in advanced/metastatic sqNSCLC, and remain more limited than for non-squamous NSCLC.

On December 6, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported preclinical data for ARV-393, a PROTAC BCL6 degrader, in combination with glofitamab, a CD20×CD3 bispecific antibody, presented in a poster at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, held December 6–9, 2025, in Orlando, Florida. In a humanized high-grade B-cell lymphoma (HGBCL) cell line–derived xenograft (CDX) model, the combination of ARV-393 and glofitamab resulted in significantly enhanced tumor growth inhibition (TGI) and increased rates of tumor regression compared with either agent alone. These preclinical data suggest mechanistic synergies between BCL6 degradation with ARV-393 and T-cell engagement.

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"Despite advances in treatment options, many patients with diffuse large B-cell lymphoma continue to face limited options once standard therapies fail. By pursuing a chemotherapy-free combination approach, we aim to address this significant unmet need and potentially offer patients a more targeted, better-tolerated therapeutic alternative," said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer, Arvinas. "The initiation of our Phase 1 combination clinical trial, planned for 2026, represents an important step toward defining the potential of ARV-393 in the treatment of this aggressive form of lymphoma."

Key highlights from the poster presentation include:

In a humanized HGBCL CDX model ARV-393 (3 mg/kg) combined with glofitamab (0.15 mg/kg) achieved 81% TGI with concomitant dosing and 91% TGI with sequential dosing (ARV-393 followed by glofitamab), versus 38% for single-agent ARV-393 and 36% for glofitamab alone.
At a higher ARV-393 dose (6 mg/kg) combined with glofitamab (0.15 mg/kg), an increase in tumor regressions was observed with concomitant (10/10 mice) and sequential dosing (7/8 mice) vs single-agent ARV-393 (5/11 mice) or glofitamab (0/11 mice).
RNA sequencing and biomarker analyses revealed that ARV-393 upregulated CD20 expression and genes that promote interferon signaling and antigen presentation, while downregulating proliferation-associated gene sets. These collective effects likely contributed to the observed synergistic antitumor activity.

"We believe these results underscore the potential for ARV-393 and provide a strong mechanistic rationale for exploring ARV-393 in combination with glofitamab as a chemotherapy-free treatment strategy for patients with diffuse large B-cell lymphoma," said Angela Cacace, Ph.D., Chief Scientific Officer, Arvinas. "These preclinical results support our belief in the clinical potential and combinability of ARV-393 and the possibility to provide real benefit to patients in need."

ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma and Arvinas plans to share clinical data from this trial at a medical congress in 2026. Additionally, Arvinas plans to add a glofitamab combination cohort in patients with DLBCL in the ongoing Phase 1 clinical trial of ARV-393 in 2026.

About ARV-393

ARV-393 is an investigational, orally bioavailable PROTAC designed to specifically target and degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. During B-cell development, tightly controlled BCL6 protein expression regulates >600 genes to facilitate rapid B-cell proliferation and tolerance of somatic hypermutation and gene recombination for antibody generation. Deregulated BCL6 expression is common in B-cell lymphoma and promotes cancer cell survival, proliferation, and genomic instability. PROTAC-mediated degradation has the potential to address the historically undruggable nature of BCL6.

(Press release, Arvinas, DEC 6, 2025, View Source [SID1234661193])