On December 11, 2022 CTI BioPharma Corp. (Nasdaq: CTIC) reported an oral presentation and two poster presentations from the Company’s pacritinib program at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place in New Orleans, Louisiana and virtually December 10-13, 2022 (Press release, CTI BioPharma, DEC 11, 2022, View Source [SID1234625017]).

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A new post-hoc data analysis from the Phase 3 PERSIST-2 trial of pacritinib, a novel JAK2/IRAK1 inhibitor approved by the U.S. Food and Drug Administration (FDA) for patients with myelofibrosis and severe thrombocytopenia (platelet count below 50 x 109/L), highlights pacritinib’s potential anemia benefit in patients with myelofibrosis through its inhibition of Activin A receptor type 1 (ACVR1).

"The ACVR1/hepcidin pathway has a major role in the control of anemia in patients with myelofibrosis. Importantly, pacritinib has now been shown to be a potent ACVR1 inhibitor that reduces hepcidin levels in vitro. Furthermore, in the PERSIST-2 trial, at the approved dose of 200 mg twice daily (BID), treatment with pacritinib led to transfusion independence in patients with myelofibrosis who required red blood cell (RBC) transfusions," said Dr. Stephen Oh, MD, PhD, Associate Professor of Medicine, Hematology Division at Washington University School of Medicine in St. Louis. "As anemia poses a substantial burden for patients with myelofibrosis, the potential role of pacritinib in addressing anemia is highly encouraging."

"As our understanding of the mechanism of action of pacritinib expands, the full potential of pacritinib as a therapy for cytopenic myelofibrosis is emerging," said Adam Craig, MD, PhD, President and Chief Executive Officer of CTI BioPharma. "We continue in our commitment to meaningfully change the treatment paradigm for cytopenic myelofibrosis."

Presentation materials will be available at ctibiopharma.com.

The details of the oral presentation are as follows:

Pacritinib Is a Potent ACVR1 Inhibitor with Significant Anemia Benefit in Patients with Myelofibrosis

Abstract Number: 628
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Towards Personalized Medicine in Myeloproliferative Neoplasms and Mastocytosis: New and Repurposed Drugs for Unmet Clinical Needs
Session Date: Sunday, December 11, 2022
Presentation Time: 5:15–5:30 p.m. CST/6:15–6:30 p.m. EST
Presenter: Dr. Stephen Oh

Pacritinib is a novel JAK2/IRAK1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and severe thrombocytopenia (platelet count <50 x 109/L) and can be administered at the full approved dose (200 mg BID) regardless of cytopenias. Pacritinib demonstrated hemoglobin improvement in the randomized Phase 3 PERSIST-2 study, though the mechanism behind and the extent of pacritinib’s anemia benefit has not been fully described. A retrospective analysis of the Phase 3 PERSIST-2 study was performed to assess pacritinib’s in vitro potency against ACVR1 and its ability to reduce hepcidin and to describe the impact of pacritinib 200 mg BID on RBC transfusion independence.

Results from in vitro testing suggest pacritinib is a potent ACVR1 inhibitor that reduces hepcidin expression. Analysis of the clinical data shows that pacritinib therapy results in transfusion independence in patients with myelofibrosis who require RBC transfusions. Given this unique mechanism of action, pacritinib may provide a therapeutic option that provides spleen, symptom and anemia benefits to patients with myelofibrosis.

The details of the poster presentations are as follows:

Differential Impact of Thrombocytopenia and Anemia on Myelofibrosis (MF) Symptom Burden

Abstract Number: 1712
Session Name: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Session Date: Saturday, December 10, 2022
Presentation Time: 5:30–7:30 p.m. CST/6:30–8:30 p.m. EST
Presenter: Dr. Jeanne Palmer

Patients with myelofibrosis and thrombocytopenia (platelet count <50 x 109/L) report worse fatigue, inactivity, early satiety and quality of life compared to patients with higher platelet counts. Because thrombocytopenia and anemia frequently co-occur in myelofibrosis, the relative impact of thrombocytopenia and anemia on myelofibrosis symptoms is unknown. A retrospective analysis of baseline data from the Phase 3 PERSIST-1 and Phase 2 PAC203 trials was performed to describe the differential impact of thrombocytopenia and anemia on symptom burden by analyzing symptom data from patients with myelofibrosis who have isolated thrombocytopenia (platelet count <100 x 109/L and hemoglobin ≥8 g/dL) versus isolated anemia (platelet count ≥100 x 109/L and hemoglobin <8 g/dL).

Results showed that patients with isolated thrombocytopenia had more severe symptom burden than those with isolated anemia, particularly with physical function- and spleen-related symptoms. While amelioration of anemia is an important therapeutic goal for patients with cytopenic myelofibrosis, these data suggest that additional efforts aimed at the control of platelet count and underlying disease should be implemented to achieve optimal symptom control.

PACIFICA: A Randomized, Controlled Phase 3 Study of Pacritinib Versus Physician’s Choice in Patients with Primary or Secondary Myelofibrosis and Severe Thrombocytopenia

Abstract Number: 4316
Session Name: 631. Myeloproliferative Syndromes and Chronic Myeloid Leukemia: Basic and Translational: Poster III
Session Date: Monday, December 12, 2022
Presentation Time: 6:00–8:00 p.m. CST/7:00–9:00 p.m. EST
Presenter: Dr. John Mascarenhas

Pacritinib is a novel JAK2/IRAK1/ACVR1 inhibitor approved by the U.S. FDA for patients with myelofibrosis and severe thrombocytopenia (platelet count <50 x 109/L). So far, treatment options for patients with myelofibrosis and severe thrombocytopenia are limited due to the high incidence of treatment-related thrombocytopenia when other JAK inhibitors are used. Previously, pacritinib demonstrated clinical activity in myelofibrosis in two Phase 3 studies (PERSIST-1 and PERSIST-2) and a Phase 2 dose-finding study (PAC203), all of which included patients with severe thrombocytopenia. PACIFICA is a multinational, multicenter, 2:1 randomized, controlled Phase 3 trial (NCT03165734) designed to confirm the efficacy and safety of pacritinib 200 mg twice daily vs physician’s choice therapy in patients with myelofibrosis and severe thrombocytopenia.

About VONJO (pacritinib)
Pacritinib is an oral kinase inhibitor with activity against wild type Janus Associated Kinase 2 (JAK2), mutant JAK2V617F form, IRAK1, ACVR1 (ALK2) and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Myelofibrosis is often associated with dysregulated JAK2 signaling. At clinically relevant concentrations, pacritinib does not inhibit JAK1.

VONJO is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 x 109/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). CTI is conducting the Phase 3 PACIFICA study of VONJO in patients with myelofibrosis and severe thrombocytopenia as a post-marketing requirement.

Important VONJO Safety Information
Hemorrhage:
Serious (11%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <100 x 109/L. Serious (13%) and fatal (2%) hemorrhages have occurred in VONJO-treated patients with platelet counts <50 x 109/L. Grade ≥3 bleeding events (defined as requiring transfusion or invasive intervention) occurred in 15% of patients treated with VONJO compared to 7% of patients treated on the control arm. Due to hemorrhage, VONJO dose reductions, dose interruptions, or permanent discontinuations occurred in 3%, 3%, and 5% of patients, respectively.

Avoid use of VONJO in patients with active bleeding and hold VONJO seven days prior to any planned surgical or invasive procedures. Assess platelet counts periodically, as clinically indicated. Manage hemorrhage using treatment interruption and medical intervention.

Diarrhea:
VONJO causes diarrhea in approximately 48% of patients compared to 15% of patients treated on the control arm. The median time to resolution in VONJO-treated patients was two weeks. The incidence of reported diarrhea decreased over time, with 41% of patients reporting diarrhea in the first eight weeks of treatment, 15% in weeks 8 through 16, and 8% in weeks 16 through 24. Diarrhea resulted in treatment interruption in 3% of VONJO-treated patients. None of the VONJO-treated patients reported diarrhea that resulted in treatment discontinuation. Serious diarrhea adverse reactions occurred in 2% of patients treated with VONJO compared to no such adverse reactions in patients in the control arm.

Control pre-existing diarrhea before starting VONJO treatment. Manage diarrhea with antidiarrheal medications, fluid replacement, and dose modification. Treat diarrhea with antidiarrheal medications promptly at the first onset of symptoms. Interrupt or reduce VONJO dose in patients with significant diarrhea despite optimal supportive care.

Thrombocytopenia:
VONJO can cause worsening thrombocytopenia. VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre-existing moderate to severe thrombocytopenia (platelet count <100 x 109/L). VONJO dosing was reduced due to worsening thrombocytopenia in 2% of patients with pre-existing severe thrombocytopenia (platelet count <50 x 109/L).

Monitor platelet count prior to VONJO treatment and as clinically indicated during treatment. Interrupt VONJO in patients with clinically significant worsening of thrombocytopenia that lasts for more than seven days. Restart VONJO at 50% of the last given dose once the toxicity has resolved. If toxicity recurs hold VONJO. Restart VONJO at 50% of the last given dose once the toxicity has resolved.

Prolonged QT interval:
VONJO can cause prolongation of the QTc interval. QTc prolongation of >500 msec was higher in VONJO-treated patients than in patients in the control arm (1.4% vs 1%). QTc increase from baseline by 60 msec or higher was greater in VONJO-treated patients than in control arm patients (1.9% vs 1%). Adverse reactions of QTc prolongation were reported for 3.8% of VONJO-treated patients and 2% of control arm patients. No cases of torsades de pointes were reported.

Avoid use of VONJO in patients with a baseline QTc of >480 msec. Avoid use of drugs with significant potential for QTc prolongation in combination with VONJO. Correct hypokalemia prior to and during VONJO treatment. Manage QTc prolongation using VONJO interruption and electrolyte management.

Major Adverse Cardiac Events (MACE):
Another JAK)-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with VONJO, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

Thrombosis:
Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which VONJO is not indicated.

Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

Secondary Malignancies:
Another JAK-inhibitor has increased the risk of lymphoma and other malignancies, excluding non-melanoma skin cancer (NMSC) (compared to those treated with TNF blockers), in patients with rheumatoid arthritis, a condition for which VONJO is not indicated. Patients who are current or past smokers are at additional increased risk.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with VONJO, particularly in patients with a known malignancy (other than a successfully-treated NMSC), patients who develop a malignancy, and patients who are current or past smokers.

Risk of Infection:
Another JAK-inhibitor has increased the risk of serious infections compared to best available therapy (BAT) in patients with myeloproliferative neoplasms. Serious bacterial, mycobacterial, fungal and viral infections may occur in patients treated with VONJO. Delay starting therapy with VONJO until active serious infections have resolved. Observe patients receiving VONJO for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

Interactions with CYP3A4 Inhibitors or Inducers:
Co-administration of VONJO with strong CYP3A4 inhibitors or inducers is contraindicated. Avoid concomitant use of VONJO with moderate CYP3A4 inhibitors or inducers.

Drug interruptions due to an adverse reaction occurred in 27% patients who received VONJO 200 mg twice daily compared to 10% of patients treated with BAT. Dosage reductions due to an adverse reaction occurred in 12% of patients who received VONJO 200 mg twice daily compared to 7% of patients treated with BAT. Permanent discontinuation due to an adverse reaction occurred in 15% of patients receiving VONJO 200 mg twice daily compared to 12% of patients treated with BAT.

Please visit View Source for full Prescribing Information and the Medication Guide.

About Myelofibrosis
Myelofibrosis is bone marrow cancer that results in formation of fibrous scar tissue and can lead to thrombocytopenia and anemia, weakness, fatigue and an enlarged spleen and liver. Within the United States, there are approximately 21,000 patients with myelofibrosis, 7,000 of which have severe thrombocytopenia (defined as blood platelet counts of less than 50 x 109/L). Severe thrombocytopenia is associated with poor survival and high symptom burden and can occur as a result of disease progression or from drug toxicity with other JAK2 inhibitors, such as JAKAFI and INREBIC.

On December 11, 2022 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported positive updated clinical data from its ongoing Phase 2 APEX clinical trial evaluating the selective KIT D816V inhibitor bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) (Press release, Cogent Biosciences, DEC 11, 2022, View Source [SID1234625014]). The data are being presented in an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in New Orleans, LA.

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"Advanced systemic mastocytosis is a rare and life-threatening disease," said Daniel J. DeAngelo, M.D., Ph.D., Chief of the Division of Leukemia at the Dana-Farber Cancer Institute and APEX clinical trial investigator. "Updated results from the APEX trial demonstrate rapid and deep responses with bezuclastinib while maintaining an impressive safety and tolerability profile."

"We are very encouraged by the clinical profile that bezuclastinib has shown to date," said Andrew Robbins, President and Chief Executive Officer at Cogent Biosciences. "We are especially excited that a growing body of data supports bezuclastinib’s differentiated safety and tolerability profile enabling therapeutic exposures that could support key differentiation for both AdvSM patients and non-advanced systemic mastocytosis patients."

Updated Data from Ongoing Phase 2 APEX Clinical Trial
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. As of the data cutoff date of October 26, 2022, 16 patients had been treated in Part 1 at one of four dose levels (50 mg BID, 100 mg BID, 200 mg BID or 400 mg QD). The median age of patients at study entry was 69 years (ranging from 33-87 years). Patients were enrolled with the following sub-types: three patients with aggressive systemic mastocytosis (ASM), 12 patients with systemic mastocytosis with associated hematologic neo-plasm (SM-AHN), and one patient with mast cell leukemia (MCL). Three patients had received prior avapritinib and midostaurin treatment.

Updated Safety Data
As of the cutoff date October 26, 2022, bezuclastinib was generally well-tolerated at all doses. The majority of adverse events were Grade 1/2 and occurred in no more than one patient. Grade 3 events reported as at least possibly related to bezuclastinib were neutropenia (2 patients), thrombocytopenia (1 patient), anemia (1 patient) and hypersensitivity/mediator flare (1 patient). Importantly, there were no related cases of cognitive impairment and no reported intracranial bleeding events, which have been associated with other KIT inhibitors. Limited low-grade edema was observed, and analysis of platelet counts in bezuclastinib-treated patients showed no trend in platelet reduction at any dose.

Updated Clinical Activity Data
As of the cutoff date of October 26, 2022, 11 patients were evaluable for response per the modified IWG-MRT-ECNM criteria, and 12 patients were evaluable for response using pure pathological response (PPR) criteria. Reported ORR per mIWG-MRT-ECNM criteria includes centrally adjudicated confirmed and unconfirmed CR, CRh, PR, and CI.

89% ORR in TKI therapy naïve patients, including 67% of patients achieving CR, CRh or PR, and 22% of patients achieving CR or CRh
73% ORR in all patients, regardless of prior treatment
75% ORR in all patients by PPR criteria, regardless of prior treatment
Additionally, results of key markers of clinical activity were reported from 16 patients.

14/16 patients achieved ≥ 50% reduction in serum tryptase levels by central assessment
85% median reduction in serum tryptase
Eight of these patients achieved reduction to <20 ng/mL
13/13 patients with ≥2 cycles of treatment achieved ≥50% reduction in bone marrow mast cells by central review
10 of these patients achieved complete clearance of bone marrow mast cell aggregates
11/12 patients with baseline D816V mutation and ≥2 cycles of treatment achieved ≥50% reduction in KIT D816V variant allele fraction (VAF) by droplet digital polymerase chain reaction (ddPCR)
Bezuclastinib Clinical Development
Based on the continued favorable safety and tolerability profile and clinical activity observed to date in the Phase 2 APEX clinical trial with bezuclastinib for patients with AdvSM, Cogent will continue enrolling patients in Part 1 of APEX to determine a recommended dose for use in Part 2 of the trial.

In addition, Cogent continues to actively enroll patients in SUMMIT, a Phase 2 clinical trial with bezuclastinib for patients with non-advanced systemic mastocytosis (NonAdvSM), and PEAK, a registrational randomized, open-label, global, Phase 3 clinical trial in patients with imatinib-resistant Gastrointestinal Stromal Tumors (GIST). Cogent plans to present initial clinical efficacy results from the PEAK lead-in study during the first half of 2023 and present initial clinical data from SUMMIT in the second half of 2023.

Webcast Information & ASH (Free ASH Whitepaper) Poster
Cogent will host a webcast on December 12, 2022 at 8:00 a.m. ET (7:00 a.m. CT) to discuss today’s updated clinical data from the ongoing APEX trial. The live event can be accessed on the Investor 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) poster is available to registered conference attendees as well as on the Posters and Publications section of Cogent’s website at www.cogentbio.com/research.

On December 11, 2022 Boston Scientific Corporation (NYSE: BSX) and Acotec Scientific Holdings Limited ("Acotec" and 6669.HK) reported that Boston Scientific will make a partial offer to acquire a majority stake, up to a maximum of 65%, of shares of Acotec, a Chinese medical technology company that offers solutions designed for a variety of interventional procedures (Press release, Boston Scientific, DEC 11, 2022, View Source [SID1234625013]). The proposed price is HK$20 per share, which represents a total upfront cash payment consideration of approximately US$523 million for the 65% stake at current exchange rates.i

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Acotec is a leader in innovative medical solutions, including drug-coated balloons (DCBs), which are used in the treatment of vascular and other diseases. In 2016, the company launched the first peripheral DCB in China after receiving approval from the National Medical Products Administration. The Acotec portfolio also includes radiofrequency ablation technologies and thrombus aspiration catheters, as well as more than 20 other products in various stages of development across a range of specialties. In the 12-month period ending June 30, 2022, Actotec generated sales of RMB 339 million (approximately US$53 million), growing 25% year-over-year in the first six months of 2022 with strong double-digit growth in each of the two years prior.ii

"Acotec is a profitable, fast-growing company with a strong portfolio and innovative pipeline of medical technologies, and we believe this investment will generate growth opportunities for both companies," said Art Butcher, executive vice president and group president, MedSurg and Asia Pacific, Boston Scientific. "We expect completion of the partial offer to further strengthen our presence in China and create the potential for commercialization of Acotec products globally, providing an increased number of physicians and patients access to our robust and complementary product portfolios."

Boston Scientific expects the impact to adjusted earnings per share to be immaterial in 2023 and the impact to GAAP earnings per share to be less accretive, or dilutive, as the case may be, due to amortization expense and acquisition-related net charges.

The completion of the transaction, which is anticipated in the first half of 2023, is subject to acceptance and approval by Acotec shareholders and other conditions set forth in related filings.

Additional information about this investment is available on the Events and Presentations section of the Boston Scientific investor relations website.

On December 11, 2022 Bellicum Pharmaceuticals, Inc. (Nasdaq: BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported a poster presentation by the University of North Carolina Lineberger Comprehensive Cancer Center (UNC Lineberger) team at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held in New Orleans December 10-13, 2022 (Press release, Bellicum Pharmaceuticals, DEC 11, 2022, View Source [SID1234625011]). The presentation, scheduled for today at 6 p.m. CT, will provide data on four patients who received rimiducid to activate the CaspaCIDe safety switch in an investigator sponsored trial.

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The poster titled "Abrogation of Immune Effector Cell Neurotoxicity Syndrome (ICANS) By Rimiducid (RIM) in Patients Treated with CD19-Specific Chimeric Antigen Receptor Modified T-Cells (CAR-T) Engineered with an Inducible Caspase 9 (iC9 CAR.19)" will also be available on Bellicum’s website.

The UNC Lineberger research team reported the clinical and pharmacodynamic courses of ICANS for four patients treated with rimiducid in an ongoing cell dose expansion cohort of a Phase I/II trial of iC9 CAR.19 cells to treat B-lymphoblastic leukemia (B-ALL). According to the poster, rimiducid administration to these patients experiencing corticosteroid-unresponsive grade 3-4 ICANS was associated with abrupt reduction of circulating iC9 CAR.19 cells and lower ICANS grade within 24 hours. The UNC Lineberger research team concluded that iC9 holds promise as a tool to potentially abrogate the most severe CAR T-cell toxicities.

"There is an unmet need in the management of severe ICANS, and these results suggest that the iC9 switch may mitigate such life-threatening toxicities," commented Natalie Grover, M.D., clinical director of UNC Lineberger’s cellular therapy program. "We look forward to further studies to explore ways to manage adverse reactions and improve patient outcomes for cellular immunotherapy regimens."

"These encouraging findings from UNC reinforce the potential benefit of the CaspaCIDe safety switch and rimiducid in resolving CAR T-cell related adverse events," said Rick Fair, President & CEO of Bellicum Pharmaceuticals. "We continue to support further clinical evaluation of the technology and remain committed to incorporating this important safety feature more broadly in additional cell therapies."

The UNC Lineberger team is exploring lower doses of rimiducid to determine if—by preserving a higher percentage of CAR-T cells—toxicity may be mitigated without diminishing the therapeutic benefit.

On December 11, 2022 AbbVie (NYSE: ABBV) reported data from multiple clinical trials evaluating epcoritamab (DuoBody-CD3xCD20), an investigational subcutaneous bispecific antibody, alone or in combination for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL), previously untreated FL, R/R diffuse large B-cell lymphoma (DLBCL), as well as Richter’s syndrome at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, AbbVie, DEC 11, 2022, View Source [SID1234625009]).

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Notably, initial results of investigational epcoritamab in patients with R/R FL and previously untreated FL are featured during session 623 on Sunday, December 11 starting at 4:30 p.m. CST. The results are part of the EPCORE NHL-2 study, a Phase 1b/2, open-label trial to assess the safety and preliminary efficacy of epcoritamab in combination with other agents in patients with B-cell non-Hodgkin’s lymphoma, including FL. Approximately 2.7 per 100,000 people in the U.S. are newly diagnosed with FL every year and the median age of patients at diagnoses with FL is 63.1,2,3 FL is typically a slow-growing or indolent form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.4 Although FL is a slow-growing lymphoma, it is considered incurable with conventional therapy.5,6

"These data at this year’s ASH (Free ASH Whitepaper) meeting are promising as they support continued investigation of epcoritamab for patients in need of new treatment options for follicular lymphoma and other B-cell lymphomas," said Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie. "Along with Genmab, we look forward to continuing to build on our promise of exploring a potential core therapy for patients with B-cell malignancies in a variety of treatment settings."

Additional results from the EPCORE NHL-2 study as well as the EPCORE CLL-1 study were presented for investigational epcoritamab in R/R DLBCL and Richter’s syndrome respectively. The EPCORE CLL-1 study is an open-label, multi-center, safety and efficacy trial of epcoritamab in R/R chronic lymphocytic leukemia (CLL) and Richter’s syndrome. The trial consists of two parts, a dose escalation Phase (Phase Ib) and an expansion Phase (Phase II).7

Abstract #609: Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update

Oral Presentation: Sunday, December 11, 2022 at 5:00 p.m. CST

In the R/R FL arm of the EPCORE NHL-2 trial, 95 percent (63/66) of efficacy-evaluable patients treated with subcutaneous epcoritamab in combination with rituximab and lenalidomide achieved an overall response rate (ORR) and 80 percent (53/66) achieved complete metabolic response (CMR). The majority of patients achieved a response at first tumor response assessment and most continued to respond through the latest assessment at the time of data collection.

A manageable cytokine release syndrome (CRS) occurrence was observed with only low-grade events, mainly following the first full dose, all of which resolved. The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (47%), CRS (43%), injection-site reactions (32%), fatigue (31%), constipation (25%), COVID-19 (25%), pyrexia (25%) and infusion-related reaction (21%).

Abstract #611: Subcutaneous Epcoritamab in Combination with Rituximab + Lenalidomide for First-Line Treatment of Follicular Lymphoma: Initial Results from Phase 1/2 Trial

Oral Presentation: Sunday, December 11, 2022 at 5:30 p.m. CST

In the previously untreated FL patient arm of the EPCORE NHL-2 trial, 94 percent (34/36) of efficacy-evaluable patients who received subcutaneous epcoritamab in combination with rituximab and lenalidomide achieved an ORR, including 86 percent (31/36) achieving CMR as their best overall response. In the trial, the investigational combination therapy showed a manageable CRS occurrence with only low-grade events, all of which resolved.

The most common TEAEs of any grade were CRS (54%), neutropenia (47%), pyrexia (44%), fatigue (37%), injection-site reaction (37%), headache (34%), COVID-19 (33%), diarrhea (32%), constipation (29%), rash (27%), increased alanine aminotransferase (ALT) (22%), and vomiting (22%).

Abstract #443: Subcutaneous Epcoritamab + R-Dhax/C in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Eligible for Autologous Stem Cell Transplant: Updated Phase 1/2 Results

Oral Presentation: Sunday, December 11, 2022 at 10:30 a.m. CST

Results from the EPCORE NHL-2 arm evaluating 27 patients with R/R DLBCL who were eligible for autologous stem cell transplant, showed an 85 percent (23/27) ORR and 67 percent (18/27) CMR following treatment with the combination of subcutaneous epcoritamab plus standard rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C) salvage therapy.

The most common TEAEs of any grade were thrombocytopenia (69%), anemia (51%), neutropenia (44%), CRS (41%), nausea (31%), fatigue (28%), constipation (24%), diarrhea (24%), headache (24%), pyrexia (24%) and increased aspartate aminotransferase (AST) (21%). All CRS events were low-grade and resolved.

Abstract #348: Subcutaneous Epcoritamab in Patients with Richter’s Syndrome: Early Results from Phase 1b/2 Trial (EPCORE CLL-1)

Oral Presentation: Saturday, December 10, 2022 at 5:15 p.m. CST

Preliminary results from the EPCORE CLL-1 trial showed that treatment with subcutaneous epcoritamab monotherapy had promising antitumor activity in 10 patients with Richter’s syndrome, with a 60 percent ORR and a 50 percent CMR rate. Most responses were observed by the first assessment at week six. In the trial, patients experienced only low-grade CRS events, mostly associated with the first full dose, all of which resolved.

The most common TEAEs of any grade were CRS (90%), anemia (50%), neutropenia (50%), injection-site reaction (40%), thrombocytopenia (40%), hypophosphatemia (30%), Hypokalemia (30%), hyperglycemia (30%), COVID-19 (30%), diarrhea (30%), fatigue (30%), and nausea (30%).

About Diffuse Large B-Cell Lymphoma (DLBCL)
DLBCL is a fast-growing type of NHL that affects B-cell lymphocytes, a type of white blood cell.8 It is the most common type of NHL worldwide and accounts for approximately 30 percent of all NHL cases.8 DLBCL can arise in lymph nodes, as well as in organs outside of the lymphatic system.8 The disease occurs more commonly in the elderly and is slightly more prevalent in men.8

About Richter’s Syndrome
Richter’s syndrome, also known as Richter’s transformation, is defined as the transformation of CLL into an aggressive lymphoma, most commonly DLBCL.9,10 Richter’s syndrome occurs in approximately 2 percent to 10 percent of CLL patients during the course of their disease.9

About the EPCORE NHL-2 Trial
EPCORE NHL-2 is a Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard-of-care agents in subjects with B-cell non-Hodgkin’s lymphoma. The trial consists of two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion).11

The primary objective of Part 1 is safety, and it includes Arm 1–5. Part 2 includes all 8 arms (Arm 1–8) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Patients in Arm 1–5 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities will be assessed in Part 1 and for a selected number of patients in Arm 8 during a 28-day period (safety-run Phase). The arms are conducted in parallel.11

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. 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.12 CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, FL, mantle cell lymphoma and CLL.13,14

AbbVie recently announced that the Biologics License Application (BLA) for epcoritamab for the treatment of adult patients with R/R large B-cell lymphoma after two or more lines of systemic therapy was accepted for priority review by the U.S. Food and Drug Administration. Additionally, the European Medicines Agency has validated a Marketing Authorization Application for epcoritamab for the treatment of adult patients with R/R DLBCL after two or more lines of systemic therapy.

Epcoritamab is being co-developed by AbbVie and Genmab 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. The companies are committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes an ongoing Phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) and a Phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R FL (NCT: 05409066).