On December 8, 2024 Orca Bio, a late-stage biotechnology company committed to transforming the lives of patients through high-precision cell therapy, reported clinical findings on the use of Orca-Q, its investigational second-generation allogeneic T-cell immunotherapy, without the use of any graft versus host disease (GvHD) prophylaxis in patients with diverse hematological conditions at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Orca Bio, DEC 8, 2024, View Source;utm_medium=rss&utm_campaign=orca-bio-presents-three-year-survival-data-with-orca-t-in-patients-with-hematological-malignancies-at-the-66th-ash-annual-meeting [SID1234648873]).

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Preliminary data from a subset of the multicenter Phase 1 clinical trial of Orca-Q in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelofibrosis (MF) showed encouraging patient outcomes without the use of GvHD prophylaxis, including low rates of GvHD, infection and non-relapse mortality (NRM) in patients with fully matched donors.

"With a conventional allogeneic stem cell transplant, patients typically receive a mix of strong immunosuppressive drugs to control GvHD. These can also lead to poor immune reconstitution and increase the risk of infections, organ damage and relapse," said presenting author Mehrdad Abedi, MD, hematologist and professor of Medicine at UC Davis Comprehensive Cancer Center. "The possibility of achieving a cure without the need for preventative agents could expand the treatment landscape for patients with hematologic malignancies. While additional data is needed, these early findings suggest Orca-Q without GvHD prophylaxis may have the potential to transform our treatment approach."

This analysis evaluated 14 patients enrolled in the HLA-identical donor dose expansion arm who received myeloablative conditioning (MAC) with Orca-Q and either busulfan, fludarabine and thiotepa (BFT) or total body irradiation-based conditioning (TBI). Across all patients, the median time to engraftment of neutrophils and platelets was 11 days and rates of GvHD and serious infections were low. In the subgroup of patients who received Orca-Q and BFT, there was no chronic GvHD of any grade and two cases of grade 2 acute GvHD. There were no cases of non-relapse mortality (NRM) reported across all 14 patients. Relapse-free survival (RFS) and overall survival (OS) were both 85% among all patients, and both 90% in the BFT population. GvHD-free, relapse-free survival (GRFS) was 77% and 90% across all patients and in the BFT group, respectively.

Across all patients, Orca-Q was manufactured reliably and delivered with vein-to-vein times of 72 hours or less across the U.S.

"Our team is inspired by the possibility of developing a product that could eliminate the need for GvHD prophylaxis while preserving safety and efficacy, a concept representing a significant advancement for hematology and beyond," said Nate Fernhoff, PhD, co-founder and chief scientific officer at Orca Bio. "We are highly encouraged by these preliminary data which provide an early glimpse into the future therapeutic potential of Orca-Q."

About Orca-Q
Orca-Q is Orca Bio’s second-generation investigational allogeneic T-cell immunotherapy being evaluated in clinical trials for the treatment of multiple hematologic malignancies, including in patients with haploidentical donors. Orca-Q is a proprietary composition of stem cells combined with specific T-cell subsets derived from healthy donors and engineered by Orca Bio’s high-precision platform.

On December 8, 2024 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported positive updated data from Part 1 of the Company’s ongoing Phase 2 APEX clinical trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2024) Annual Meeting & Exposition taking place December 7-10, 2024 in San Diego, CA (Press release, Cogent Biosciences, DEC 8, 2024, View Source [SID1234648872]).

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"Bezuclastinib has the potential to transform the treatment landscape for people living with advanced systemic mastocytosis," said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and Professor of Medicine, Harvard Medical School. "The impressive clinical data presented today from APEX Part 1 demonstrates a combination of rapid and deep clinical responses, with a safety profile that avoids several of the most concerning side effects for AdvSM patients today."

"We are excited to share today the updated clinical data from APEX Part 1 studying bezuclastinib in patients with advanced systemic mastocytosis," said Andrew Robbins, Cogent’s President and Chief Executive Officer. "These results show the enormous promise that a highly potent, highly selective, non-brain penetrant KIT inhibitor may provide to this patient population. We look forward to completing enrollment in APEX Part 2 and sharing the results from that study in mid-2025."

Patient Demographics
APEX is a global, open-label, multi-center, two-part Phase 2 clinical trial in patients with AdvSM evaluating the safety, efficacy, pharmacokinetic, and pharmacodynamic profiles of bezuclastinib. Thirty-two patients were treated in Part 1 at one of four dose levels (50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). Earlier this year, Cogent announced APEX Part 2 would be conducted at the optimized 150mg QD dose, which closely matches the exposure from 100 mg BID dose in APEX Part 1. The median age of patients at study entry was 68 years (ranging from 33-87 years). Patients were enrolled with the following sub-types: seven patients with aggressive systemic mastocytosis (ASM), 23 patients with systemic mastocytosis with associated hematologic neoplasm (SM-AHN), and two patients with mast cell leukemia (MCL). Five patients had received prior avapritinib and 10 patients had received prior midostaurin treatment.

Clinical Activity Data
As of the data cutoff date of October 11, 2024, 32 patients enrolled were evaluated for signs of clinical activity, 27 of whom were mIWG-MRT-ECNM evaluable. Clinical activity analyzed across dose levels and focused on 100 mg BID cohort showed:

52% ORR (CR+CRh+PR+CI) per mIWG-MRT-ECNM criteria, including 61% ORR for TKI-treatment-naïve patients
83% ORR for patients treated at 100 mg BID dose cohort
88% ORR (CR+PR) per pure pathological response (PPR) criteria
100% ORR for patients treated at 100 mg BID dose cohort
Median time to achieve response was 2.2 months and median duration of response has not yet been reached
Median PFS was not yet reached at median follow-up of 20 months; PFS rate at 24 months was 82%
Pharmacodynamic Data
Nearly all patients demonstrated a significant improvement in biomarkers associated with disease burden. Patients without post baseline biomarker data were excluded from relevant analyses.

94% of patients achieved ≥50% reduction in serum tryptase levels
100% of patients receiving ≥2 cycles achieved ≥50% reduction
66% of patients achieved reduction of serum tryptase below 20 ng/mL

93% of KITD816V-positive patients achieved ≥50% reduction in KIT D816V variant allele fraction (VAF)

100% of evaluable patients achieved a ≥50% reduction in bone marrow mast cell burden
83% achieved complete clearance of mast cell aggregates by central review
Safety Data
As of the data cutoff date of October 11, 2024, bezuclastinib continues to demonstrate a differentiated safety and tolerability profile across doses. The majority of hematological adverse events were low grade and reversible. There have been no new treatment related serious adverse events or discontinuations reported since ASH (Free ASH Whitepaper) 2023. Due to confounding medical issues, one patient previously reported with DILI has been reassessed and reported as a Grade 4 gamma-glutamyl transferase (GGT) elevation case. Twelve patients required dose reduction, eight of whom were treated at a 400 mg daily dose.

Bezuclastinib in Systemic Mastocytosis
Cogent is actively enrolling patients into APEX Part 2 which is anticipated to complete enrollment in Q1 2025 with top-line results expected in mid-2025.

Cogent will present 24-week follow-up data from patients who participated in the Open Label Extension portion of the ongoing SUMMIT trial on Monday, December 9, 2024 at ASH (Free ASH Whitepaper). SUMMIT is a randomized, double-blind, placebo-controlled, global, multicenter Phase 2 trial evaluating bezuclastinib in patients with Nonadvanced Systemic Mastocytosis (NonAdvSM).

Webcast Information and ASH (Free ASH Whitepaper) Posters
Cogent will host a webcast on Monday, December 9, 2024 at 8:00 a.m. ET to discuss updated clinical results from both the APEX and SUMMIT ASH (Free ASH Whitepaper) presentations. The live event will be available on the Investors & Media page of Cogent’s website at investors.cogentbio.com. A replay of the webcast will be available approximately two hours after the completion of the event and will be archived for up to 30 days. The ASH (Free ASH Whitepaper) posters will be available to registered conference attendees and will also be in the Posters and Publications section of Cogent’s website at www.cogentbio.com/research.

On December 8, 2024 Novartis reported positive, longer-term results from the pivotal Phase III ASC4FIRST trial with Scemblix (asciminib) showing superior major molecular response (MMR) rates at week 961. The study compared the MMR rate of Scemblix to investigator-selected standard-of-care (SoC) tyrosine kinase inhibitors (TKIs) (imatinib, nilotinib, dasatinib and bosutinib) and to imatinib alone in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) at the week 96 evaluation, the study’s key secondary endpoints (Press release, Novartis, DEC 8, 2024, View Source [SID1234648869]). The longer-term results showed an increasing difference in Scemblix MMR rate vs. SoC, vs. imatinib and vs. 2G TKIs (nilotinib, dasatinib and bosutinib)1. Results were presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper)1.

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"These 96-week results are very encouraging for clinicians who aspire to obtain a balance of efficacy and tolerability profiles to help newly diagnosed adult CML patients achieve and maintain treatment goals," said Jorge Cortes, M.D., Director, Georgia Cancer Center. "The sustained superior efficacy, deeper and more durable responses, and favorable safety and tolerability profile compared to standard of care TKIs continue to support the promise of Scemblix as a potentially practice-changing treatment option."

The median follow-up was 2.2 years for Scemblix and investigator-selected SoC TKIs1. Over 22% more patients treated with once-daily Scemblix achieved MMR at week 96 vs. all investigator-selected SoC TKIs, and nearly 30% more patients achieved MMR at week 96 vs. imatinib alone1. The Scemblix MMR rate was 15.1% (95% CI: 2.3, 28.0; not crossing zero) higher vs. 2G TKIs (72% vs. 56.9%)1. Patients treated with Scemblix also achieved deeper rates of molecular responses (MR4 and MR4.5) compared with investigator-selected SoC TKIs1.

Overalla
Scemblix (n=201)
vs. IS SoC TKIs
(n=204) Imatinib stratumb
Scemblix (n=101)
vs. imatinib (n=102) 2G TKI stratumc
Scemblix (n=100)
vs. 2G TKIs
(n=102)
Key secondary endpoints MMR rates
at week 96 74.1% vs. 52% 76.2% vs. 47.1%
Secondary endpointsd MMR rates
at week 96 72% vs. 56.9%
MR4
at week 96 48.8% vs. 27.5% 52.5% vs. 23.5% 45% vs. 31.4%
MR4.5
at week 96 30.9% vs. 17.7% 35.6% vs. 11.8% 26% vs. 23.5%
a All patients receiving Scemblix (n=201) or investigator-selected SoC TKIs (n=204). Treatment difference after adjusting for pre-randomization selected TKI and EUTOS long-term survival (ELTS) risk groups at baseline.
b The 203 patients within the pre-randomization-selected imatinib stratum were randomized to receive either Scemblix (n=101) or imatinib (n=102). Treatment difference after adjusting for ELTS risk groups at baseline.
c The 202 patients within the pre-randomization selected 2G TKIs stratum were randomized to receive either Scemblix (n=100) or 2G TKIs (n=102: nilotinib, 48%; dasatinib, 41%; bosutinib, 11%).
d Secondary endpoints were not powered for statistical significance.
The safety profile of Scemblix at 96-weeks was consistent with the 4-year follow-up of the Phase III ASCEMBL trial, with no new safety concerns observed to date1,2,4. Fewer grade ≥3 AEs and dose adjustments to manage AEs were reported for Scemblix, and discontinuation due to AEs was more than 50% lower for Scemblix vs. both imatinib and 2G TKIs1. The most frequent AEs (≥15%) were diarrhea, headache, fatigue, musculoskeletal pain, and rash1.

Week 96 Scemblix
n=200 Imatinib
n=99 2G TKIs
n=102
Grade ≥ AEsa 44.5% 49.5% 59.8%
Discontinuation due to AEsa 5.5% 13.1% 12.7%
AEs leading to dose adjustments/interruptionsa 33% 41.4% 57.8%
aIn patients who experienced ≥1 adverse event.
Novartis also presented today at ASH (Free ASH Whitepaper) interim data from the Phase II ASC2ESCALATE dose-escalation study in both the second line (2L) and newly diagnosed Ph+ CML-CP settings5. In the analysis of 2L patients at week 24 (n=28) Scemblix demonstrated MMR rates of 42.9% and deep molecular responses (MR4 25% and MR4.5 10.7%), with a consistent safety and tolerability profile5. The most common AEs (>15%) were nausea, hypertension, and vomiting5.

"Novartis’ decades-long work in CML and deep relationships within the community have informed our Scemblix clinical trial program of over 10 years, the centerpiece of our continuing drive to address ongoing unmet medical needs for people with CML," said Jeff Legos, Executive Vice President, Global Head of Oncology Development, Novartis. "These latest findings reinforce the differentiated efficacy, safety and tolerability profile of Scemblix in newly diagnosed and previously treated adult CML patients."

Scemblix was recently granted accelerated approval in the US to treat newly diagnosed adults with Ph+ CML-CP, which together with its approval in previously treated adult patients with Ph+ CML-CP expands the population of Scemblix-eligible patients by four-fold 2. In addition, the National Comprehensive Cancer Network (NCCN) updated its Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of CML, recommending asciminib as a category 1 – preferred treatment for newly diagnosed Ph+ CML-CP and across all risk categories3.

About the ASC4FIRST Phase III Clinical Trial
ASC4FIRST (NCT04971226) is a Phase III, head-to-head, multi-center, open-label, randomized study of oral Scemblix 80 mg QD vs. IS first- or second-generation TKIs (imatinib, nilotinib, dasatinib or bosutinib) in 405 adult patients with newly diagnosed Ph+ CML-CP2,6. The trial met both primary endpoints with Scemblix demonstrating superior MMR rates at week 48 vs. investigator-selected SoC TKIs (imatinib, nilotinib, dasatinib and bosutinib) (67.7% vs. 49.0%) and imatinib alone (69.3% vs. 40.2%) as well as the secondary, non-powered endpoint for the 2G TKI stratum of (66% vs 57.8%)1,6. The study remains ongoing with further efficacy and safety readouts planned.

About the ASC2ESCALATE Phase II Study
ASC2ESCALATE (NCT05384587) is a Phase II, multicenter, single-arm, dose-escalation study of oral Scemblix 80 mg QD in both the second line (2L) and newly diagnosed (1L) Ph+ CML-CP settings in the US 5,7. While Scemblix is already approved across lines of therapy, this is the first prospective trial to assess asciminib in the 2L setting and a dose-escalation strategy of asciminib as 2L and 1L treatment for patients with CML-CP not meeting molecular milestones 5. The proportion of patients achieving MMR at 12 months in the 2L setting will be measured as the primary endpoint 5. The study remains ongoing and has completed enrollment with 196 patients (100 patients in 2L, 96 patients in 1L)5.

About Scemblix (asciminib)
Scemblix is the first CML treatment that works by Specifically Targeting the ABL Myristoyl Pocket (referred to as a STAMP inhibitor in scientific literature)4,8,9. Other currently approved CML treatments are TKIs that target the ATP-binding site (ATP-competitive)9.

In the US, Scemblix was granted accelerated approval to treat newly diagnosed adults with Ph+ CML-CP and is also approved for previously treated adult patients with Ph+ CML-CP. Outside the US, it is approved in more than 75 countries, including the EU, to treat those who have previously been treated with two or more TKIs with Ph+ CML-CP2,10,11. In some countries, including the US, Scemblix is also approved in patients with Ph+ CML-CP with the T315I mutation2,3,10.

Scemblix is being studied across multiple treatment lines for Ph+ CML-CP, both as a monotherapy and in combination2,4,6,8,10,12-24.

Patient Access and Support
Novartis, with its 20+ year history in CML, is committed to continuing to address areas of unmet patient need and reducing barriers to patient access and affordability that prevent patients from benefiting from innovation. Novartis Patient Support is available to help guide eligible patients through the various aspects of getting started on treatment including help understanding insurance coverage and identifying potential financial assistance options. Patients or providers can call 866-433-8000 or visit support.scemblix.com to learn more.

On December 8, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported the first presentation of data from the Phase 2 waveLINE-007 trial evaluating zilovertamab vedotin, Merck’s investigational antibody drug conjugate (ADC) that targets receptor tyrosine kinase-like orphan receptor 1 (ROR1), in combination with cyclophosphamide, doxorubicin and prednisone plus rituximab (R-CHP) for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, Merck & Co, DEC 8, 2024, View Source [SID1234648868]). At a pre-planned analysis, zilovertamab vedotin in combination with R-CHP achieved a 100% (n=15) complete response (CR) rate in patients treated with zilovertamab vedotin at 1.75 mg/kg. Based on the data, the study has established 1.75 mg/kg as the recommended Phase 3 dose of zilovertamab vedotin. These data are being presented for the first time today in an oral presentation (Abstract #578) at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition.

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"There is a need for additional first-line treatment options to help patients with diffuse large B-cell lymphoma, since, unfortunately, approximately 40% still experience relapsed or refractory disease after initial treatment with the current standard of care," said Dr. Muhit Ozcan, the study’s principal investigator, Ankara University School of Medicine. "These data from the Phase 2 waveLINE-007 trial are promising and support further research in the first-line setting in a larger patient population to help address this significant unmet need for patients."

"We are pleased to see these early positive results from the Phase 2 waveLINE-007 trial, in which zilovertamab vedotin demonstrated a highly promising response rate and a manageable safety profile in combination with standard of care," said Dr. Gregory Lubiniecki, vice president, oncology clinical research, Merck Research Laboratories. "We look forward to advancing our research of this investigational ROR1-directed antibody drug conjugate, which we believe has strong potential in multiple hematologic malignancies."

As announced, data from more than 20 abstracts are being presented from across a broad range of hematologic malignancies from Merck’s hematology pipeline, which includes a diverse range of investigational assets with novel modalities, at the 66th ASH (Free ASH Whitepaper) Annual Meeting and Exposition.

Study design and additional data from waveLINE-007

WaveLINE-007 is a non-randomized, open-label Phase 2 trial (ClinicalTrials.gov, NCT05406401) evaluating zilovertamab vedotin (MK-2140) in combination with R-CHP in patients with previously untreated DLBCL. The primary endpoints are safety (number of patients with dose limiting toxicity, adverse events and discontinuation due to adverse events) and CR rate based on investigator review per Lugano Response Criteria. Secondary endpoints include objective response rate (ORR) and duration of response (DOR) per Lugano Response Criteria. As of data cut-off, 36 patients were enrolled in the study to receive zilovertamab vedotin plus R-CHP intravenously on day 1 of each 21-day cycle (Q3W) for up to eight cycles. The treatment arms of the study included:

1.75 mg/kg (n=15); all 15 patients in this arm completed the trial (none discontinued)
2.0 mg/kg (n=15); 14 patients in this arm completed treatment and one patient discontinued after cycle 1 due to physician decision and was entered to safety follow-up, or
2.25 mg/kg (n=6); 5 patients in this arm completed treatment and one patient discontinued due to physician decision
The efficacy results showed a CR was achieved in combination with R-CHP in 100% (n=15) of patients receiving the 1.75 mg/kg dose of zilovertamab vedotin (CI: 95%, 78.2-100.0), 93.3% (n=14) of patients receiving the 2.0 mg/kg dose (CI: 95%, 68.1-99.8) and 100% (n=6) of patients receiving the 2.25 mg/kg dose (CI: 95%, 54.1-100.0). The total CR rate at the end of treatment was 97.2% (CI: 95%, 85.5-99.9). The median follow-up for all patients was 17.6 months (range, 7.1-24.6). The ORR was 100% (CI: 95%, 78.2-100.0) for patients receiving the 1.75 mg/kg dose, 93.3% (CI: 95%, 68.1-99.8) for patients receiving the 2.0 mg/kg dose, and 100% (CI: 95%, 54.1-100.0) for patients receiving the 2.25 mg/kg dose, all in combination with R-CHP. The median DOR has not been reached for all patients, and the total 12-month DOR was 93.5%. Based on the data, the recommended zilovertamab vedotin dose was determined to be 1.75 mg/kg.

Serious treatment-related adverse events (TRAEs) occurred in 11% (n=4) of all patients (1.75 mg/kg [n=1], 2.0 mg/kg [n=1], 2.25 mg/kg [n=2]). Grade 3-4 TRAEs occurred in 58% (n=21) of all patients. The most common of these events were neutropenia, nausea, anemia and diarrhea.

About diffuse large B-cell lymphoma

Lymphoma is cancer beginning in the lymphatic system – the network of organs, vessels and tissues that protects the body from infection. There are many subtypes of lymphoma, which are often categorized into two main types – Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). DLBCL, the most common form of NHL, is derived from white blood cells that grow rapidly and uncontrollably, enlarging the lymph nodes and often migrating to other parts of the body. DLBCL accounts for approximately 25-30% of all non-Hodgkin lymphomas worldwide. In the U.S., it is estimated that approximately 25,000 patients are diagnosed with DLBCL each year. The five-year relative survival rate for DLBCL is 60-70%.

About zilovertamab vedotin (MK-2140)

Zilovertamab vedotin is an investigational ADC that targets ROR1. ROR1 is a transmembrane protein that is overexpressed in multiple hematologic malignancies. Merck is committed to research with zilovertamab vedotin across B-cell malignancies and is establishing a robust program of clinical trials under the name waveLINE. The waveLINE program includes a Phase 2/3 study in patients with relapsed or refractory DLBCL (waveLINE-003, NCT05139017) and a Phase 3 study in treatment naïve patients with DLBCL (waveLINE-010, NCT06717347).

On December 8, 2024 Genmab (Nasdaq: GMAB) reported results from the Phase 1b/2 EPCORE CLL-1 clinical trial evaluating epcoritamab (Abstract #883), a T-cell engaging bispecific antibody administered subcutaneously, demonstrated an overall response rate (ORR) of 61 percent and a complete response (CR) rate of 39 percent in difficult-to-treat adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) treated with epcoritamab monotherapy (Press release, Genmab, DEC 8, 2024, View Source [SID1234648866]). These results, from the monotherapy expansion (EXP) cohort (n=23) of the trial, along with the first safety data from the optimization (OPT) cohort, were presented at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH) (Free ASH Whitepaper), during the ASH (Free ASH Whitepaper) Annual Meeting Press Program. The data will be presented during an oral session on December 9, 2024.

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In the EXP cohort, the median time to response was two (2.0) months and the median time to CR was 5.6 months. Among all patients in the cohort, median progression-free survival (PFS) was 12.8 months and median overall survival (OS) was not reached (median follow-up was 22.8 months). An estimated 65 percent of patients were alive at 15 months. Among 12 responders evaluable for minimal residual disease (MRD) by next-generation sequencing in peripheral blood, nine patients (75 percent) had undetectable MRD.

The most frequent non-hematologic treatment-emergent adverse events (TEAEs) in the EXP cohort were cytokine release syndrome (CRS; 96 percent), diarrhea (48 percent), peripheral edema (48 percent), fatigue (43 percent), and injection-site reaction (43 percent). Cytopenias were common (anemia, 65 percent; thrombocytopenia, 65 percent; neutropenia, 48 percent); however, most patients had baseline anemia and thrombocytopenia, suggesting that these events were largely disease-related. Three cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported (one Grade 1; two Grade 2), and there was one clinical tumor lysis syndrome (CTLS) case (Grade 2). These cases did not lead to treatment discontinuation. Four fatal TEAEs occurred – two cases of pneumonia, one case of sepsis and one case of squamous cell carcinoma of the skin.

The EXP cohort followed a 2-step step-up dose regimen, and CRS was manageable and primarily low grade (9 percent Grade 1, 70 percent Grade 2, 17 percent Grade 3). In the first data from the separate OPT cohort, which followed a 3-step step-up dose regimen, CRS severity was substantially reduced with only low-grade events (71 percent Grade 1, 12 percent Grade 2). In both cohorts, CRS events primarily occurred following the first full dose, and none led to treatment discontinuation. No ICANS or CTLS cases were reported in the OPT cohort.

"These EPCORE CLL-1 data are encouraging, especially as the majority of patients were heavily pre-treated with at least four lines of therapy," said Alexey Danilov, MD, PhD, Marianne and Gerhard Pinkus, Professor and Director of Early Clinical Therapeutics and Associate Director of the Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope. "Despite progress in treating chronic lymphocytic leukemia, there remains a tremendous need for additional therapeutic options for high-risk patients whose disease has progressed following standard chemoimmunotherapy and targeted therapies."

Additional data from the EXP cohort showed high response rates in patients with high-risk factors treated with epcoritamab, including TP53 aberrations, IGHV-unmutated disease and double-exposed disease – prognostic markers that are associated with disease progression and decreased survival.i,ii,iii In patients with TP53 aberrations (n=15), the ORR was 67 percent with a CR of 33 percent. Among patients with IGHV-unmutated disease (n=16), the ORR was 63 percent, and the CR was 44 percent. In double-refractory patients, the ORR was 53 percent, and the CR was 37 percent.

All patients in the trial had prior chemoimmunotherapy, and most patients had previously received targeted therapies such as BTK and BCL2 inhibitors (double-exposed) and had high-risk disease characteristics.

"Chronic lymphocytic leukemia is incurable, and patients often need a variety of treatments throughout their lifetime, especially if their disease has high-risk prognostic factors, has relapsed or has become refractory to the current standard-of-care, including targeted therapies," said Dr. Judith Klimovsky, Executive Vice President & Chief Development Officer, Genmab. "These early data show the potential therapeutic applicability of epcoritamab in relapsed or refractory chronic lymphocytic leukemia, and further reinforce the potential of epcoritamab as a core therapy for the treatment of B-cell malignancies."

Use of epcoritamab in CLL is not approved in the U.S. or in the EU or in any other territory. The safety and efficacy of epcoritamab for use in CLL have not been established.

About Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia, affecting over 200,000 people in the United States alone.iv Chronic lymphocytic leukemia can be classified as either slow growing (indolent) or fast growing (aggressive).v CLL is incurable, and many patients will likely relapse and progress on frontline therapies.vi Most patients will experience consecutive episodes of disease progression and will require several lines of treatment in their lifetime.vii,viii

About the EPCORE CLL-1 Trial
EPCORE CLL-1 is a Phase 1b/2, open-label, multi-center trial to evaluate the safety and preliminary efficacy of epcoritamab as a monotherapy and in combination with standard of care agents in patients with difficult-to-treat relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), R/R small lymphocytic lymphoma (SLL) and Richter’s Syndrome (RS). The trial consists of two parts: a dose-escalation phase (Phase 1b) and an expansion phase (Phase 2). Patients with RS are only included in the expansion phase. The primary objective of Phase 1b is to determine the recommended Phase 2 dose and the maximum tolerated dose as well as establish the safety profile of epcoritamab monotherapy and epcoritamab plus venetoclax in participants with R/R CLL. The purpose of Phase 2 is to assess and evaluate the preliminary efficacy, safety and tolerability profiles of epcoritamab monotherapy and epcoritamab plus venetoclax for patients with R/R CLL and SLL. Additionally, epcoritamab monotherapy and combination therapy will be evaluated in patients with RS to assess their efficacy, safety and tolerability profiles. More information on this trial can be found at View Source (NCT: 04623541).

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.ix

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. 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 five ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigator’s 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 rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (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.