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ISA to Present First Clinical Trial Data from the Phase II Study of ISA101b and Libtayo® (cemiplimab) Combination in Head and Neck Cancer at the ASCO Annual Meeting 2023

On May 25, 2023 ISA reported that it will present the first clinical data of the combination of ISA101b and Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in patients with recurrent metastatic Human Papilloma Virus type 16 (HPV16) induced head and neck cancers who progressed on pembrolizumab or nivolumab (Press release, ISA Pharmaceuticals, MAY 25, 2023, View Source [SID1234632062]).

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Patients with recurrent and/or metastatic HPV16 positive OPC who experienced disease progression during or within 6 months after prior anti-PD1 therapy were to be treated until disease progression or withdrawal. Patients that never responded to prior treatment were also included. Further information can be found on clinicaltrials.gov (NCT04398524). Recruitment in this study is ongoing; results of the complete trial will become available mid-2024.

Presentation Title: Phase 2 study of ISA101b (peltopepimut-S) and cemiplimab in patients with advanced HPV16+ oropharyngeal cancer who failed anti-PD-1 therapy
Presentation Details: Monday 5th June 2023, 1:15-4:15pm CDT
Presenting Author: Dr. Anthony Kong, Principal Investigator
Session (poster): Head and Neck Cancer
ISA101b immunotherapy targets human papillomavirus type 16 (HPV16) positive cancers. It induces strong and specific immune responses to the HPV16 virus, and (re-)establishes a powerful and targeted T-cell immune response against infected and/or cancerous cells and tissues. Re-ignition of an anti-tumor effect of anti-PD1 therapy after failure of checkpoint inhibition by the addition of a therapeutic vaccine is a unique feature.

Head-and-neck cancer can be a severe and life-threatening disease. HPV16 is a major cause of head-and-neck cancer. Recurrent and metastatic HPV16 positive OPC is a form of head-and-neck cancer with a high unmet medical need. In September 2021 the U.S. Food and Drug Administration (FDA) granted Fast Track designation to ISA101b for the treatment of recurrent and metastatic HPV16 positive OPC.

For more information, please contact us at [email protected].

INOVIO to Present at the 2023 Jefferies Healthcare Conference

On May 25, 2023 INOVIO (NASDAQ: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported that Dr. Jacqueline Shea, President and CEO, and Dr. Michael Sumner, CMO, will present at the 2023 Jefferies Healthcare Conference (Press release, Inovio, MAY 25, 2023, View Source [SID1234632061]).

2023 Jefferies Healthcare Conference
Date: Friday, June 9, 2023
Time: 8:00 AM ET
Format: Fireside Chat

During the conference, Dr. Shea and members of INOVIO’s management team will conduct one-on-one meetings with registered investors.

A webcast of the presentation will be available on the INOVIO Investor Relations Events page at View Source A replay of the webcast will be available for 90 days after the date of the presentation.

Geron Oral Presentation at Upcoming ASCO Annual Meeting to Highlight Meaningful Continuous Transfusion Independence Observed in Imetelstat-Treated Lower Risk MDS Patients in IMerge Phase 3

On May 25, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported acceptance of its IMerge Phase 3 abstract as an oral presentation at the upcoming 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Geron, MAY 25, 2023, View Source [SID1234632060]). This abstract describes statistically significant positive efficacy and safety data from the pivotal IMerge Phase 3 clinical trial evaluating the Company’s first-in-class telomerase inhibitor, imetelstat, in lower risk myelodysplastic syndromes (MDS). These data support the Company’s planned New Drug Application (NDA) submission to the U.S. FDA which is on track for June 2023, to support a potential U.S. commercial launch of imetelstat in lower risk MDS in the first half of 2024.

"We believe that imetelstat has the potential to be practice-changing in lower risk MDS based on the unprecedented durability of transfusion independence, as well as broad activity across a range of disease subtypes in IMerge Phase 3," said Faye Feller, M.D., Executive Vice President, Chief Medical Officer of Geron. "We are thrilled that these data will be featured in an oral presentation at ASCO (Free ASCO Whitepaper), where we will have a significant medical affairs presence to bring more awareness to the continuing unmet need in lower risk MDS and very much look forward to meaningful engagement with the medical community."

Details for the oral presentation are as follows:

Abstract #:7004

Title:IMerge: "Results from a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Imetelstat in Patients (pts) With Heavily Transfusion Dependent (TD) Non-Del(5q) Lower-Risk Myelodysplastic Syndromes (LR-MDS) Relapsed/Refractory (R/R) to Erythropoiesis Stimulating Agents (ESA)."

Date/Time:June 2, 2023 at 2:12 p.m. CT

Session:"Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant"

Presenter:Amer Methqal Zeidan, Yale School of Medicine

The abstract recaps top-line results from IMerge Phase 3 with a data cut-off of October 2022. As reported in January 2023, the primary endpoint of 8-week transfusion independence (TI) was met with high statistical significance (P<0.001) for imetelstat-treated patients (39.8%) vs. placebo (15.0%). Key secondary endpoint of 24-week TI and hematologic improvement erythroid (HI-E) under 2018 IWG criteria were also met with high statistical significance (P<0.001 for each) for imetelstat-treated patients vs. placebo.

In addition, the rate of 8-week TI was significantly higher with imetelstat vs. placebo across subgroups, including ring sideroblast (RS) negative patients. Median TI duration was significantly longer for imetelstat-treated patients vs. those on placebo (51.6 vs 13.3 weeks, P< 0.001). Patients receiving imetelstat had significantly higher mean hemoglobin (P < 0.001) and fewer transfusions (P = 0.042) over time than those on placebo.

In three of four genes frequently mutated in MDS, variant allele frequency (VAF) reduction was significantly greater in patients treated with imetelstat than placebo: SF3B1 (P< 0.001), TET2 (P= 0.032), DNMT3A (P= 0.019) and ASXL1 (P= NS). SF3B1 VAF reduction correlated with longer TI duration (P< 0.001).

No new safety signals were identified. The most common Grade 3/4 adverse events (AEs) were thrombocytopenia and neutropenia, with similar rates of Grade ≥3 bleeding and infections on imetelstat and placebo. In patients treated with imetelstat, cytopenias were manageable, of short duration, and > 80% were reversible to Grade ≤2 within 4 weeks.

The abstract concludes that for this lower risk MDS patient population: imetelstat demonstrated statistically significant and clinically meaningful efficacy with high 8- and 24-week TI rates, prolonged TI duration and increased hemoglobin. Also, VAF reduction and its correlation to clinical endpoints support imetelstat’s disease-modifying potential, and safety results were consistent with prior reported experience.

Full text of the abstract is available at www.asco.org.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron plans to submit a New Drug Application (NDA) in the U.S. in June 2023 and a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication.

Genprex Publishes Positive Clinical Data from Phase 1 Portion of Acclaim-1 Clinical Trial Evaluating REQORSA® Immunogene Therapy in Non-Small Cell Lung Cancer at the 2023 ASCO Annual Meeting

On May 25, 2023 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that positive data from the Phase 1 portion of its Acclaim-1 clinical trial evaluating REQORSA Immunogene Therapy in combination with Tagrisso in late-stage non-small cell lung cancer (NSCLC) were published in an abstract at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, taking place June 2-6, 2023 in Chicago, IL and online (Press release, Genprex, MAY 25, 2023, View Source [SID1234632059]).

"We are thrilled to have our abstract, which reports positive results from the Phase 1 portion of our Acclaim-1 clinical trial, published at the ASCO (Free ASCO Whitepaper) Annual meeting," said Mark Berger, MD, Chief Medical Officer at Genprex. "We are encouraged by the favorable safety profile of REQORSA, as well as the preliminary efficacy data we have observed, and we believe this data will support our advancement to the Phase 2 portion of the clinical trial."

Details of the abtract are below:

Abstract Number: e15081

Title: ACCLAIM-1 dose escalation: Determination of quaratusugene ozeplasmid and osimertinib recommended phase 2 dose (RP2D)

Session Title: Publication Only: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

Track: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

The abstract reports preliminary results from eight patients in Genprex’s Phase 1 portion of its Acclaim-1 clinical trial evaluating REQORSA Immunogene Therapy (quaratusugene ozeplasmid) with Tagrisso (osimertinib) in patients with advanced, EGFR mutant NSCLC whose disease progressed after Tagrisso. REQORSA was generally well tolerated, as there were no dose limiting toxicities. Full safety and efficacy data on the Phase 1 portion of the study will be presented at an upcoming medical meeting.

While the Phase 1 portion of the clinical trial is designed primarily to assess safety, promising efficacy results were also observed. One patient at the 0.06 mg/kg dose level, previously treated with carboplatin, pemetrexed, and osimertinib, had a partial remission (PR) by investigator evaluation and treatment is ongoing after 16 cycles, which is approximately 10.5 months. Another patient at the 0.09 mg/kg dose level, previously treated with osimertinib, has stable disease and treatment is ongoing after 14 cycles, or approximately 9 months. The extended and ongoing progression free survival (PFS) of each of these patients is significantly greater than the median PFS observed from treatment with osimertinib alone in this treatment setting in several prior clinical trials1 and is consistent with long-term PFS seen in prior clinical trials of REQORSA. PFS is the primary endpoint of both the Phase 2 expansion portion and the Phase 2 randomized portion of the Acclaim-1 trial.

"Demonstrating a favorable safety profile substantially de-risks the REQORSA development program and is a major accomplishment for Genprex," said Rodney Varner, Chairman, President and Chief Executve Officer of Genprex. "It is encouraging that several patients who were progressing on their previous therapy are now having long periods of response and stable disease in the Phase 1 portion of the study. We wish to thank the patients and investigators participating in our clinical trials and our investors who make it possible to move our drug candidates forward toward availability for patients in need."

1. CHRYSALIS-2 NSCLC clinical trial data reported at ASCO (Free ASCO Whitepaper) 2022

About Acclaim-1

The Acclaim-1 clinical trial is an open-label, multi-center Phase 1/2 clinical trial evaluating the Company’s lead drug candidate, REQORSA, in combination with Tagrisso in patients with late-stage NSCLC with activating epidermal growth factor receptor ("EGFR") mutations whose disease progressed after treatment with Tagrisso.

The enrollment of the dose escalation Phase 1 portion of the Acclaim-1 trial has been completed. The Phase 2 expansion portion of the study is expected to enroll approximately 66 patients, half of whom will have received only Tagrisso treatment and the other half will have received Tagrisso treatment and chemotherapy, to determine toxicity profiles of patients with different eligibility criteria, as well as efficacy and other endpoints. There will be an interim analysis following the treatment of 19 patients in each cohort. The Phase 2 randomized portion of the study is expected to enroll approximately 74 patients to be randomized 1:1 to receive either REQORSA and Tagrisso combination therapy or platinum-based chemotherapy. The primary endpoint of the Phase 2 portion of the trial is progression-free survival, which is defined as time from randomization to progression or death. An interim analysis will be performed at 25 events.

About REQORSA Immunogene Therapy

REQORSA Immunogene Therapy (quaratusugene ozeplasmid) for non-small cell lung cancer (NSCLC) uses Genprex’s unique, proprietary ONCOPREX Nanoparticle Delivery System, which is the first systemic gene therapy delivery platform used for cancer in human clinical trials. The active agent in REQORSA is a plasmid that expresses the TUSC2 tumor suppressor gene. REQORSA consists of the TUSC2 gene expressing plasmid encapsulated in non-viral lipid nanoparticles made from lipid molecules with a positive electrical charge. REQORSA is injected intravenously and specifically targets cancer cells. Once REQORSA is taken up into a cancer cell, the TUSC2 gene is expressed, and the TUSC2 protein is capable of restoring certain defective functions arising in the cancer cell. REQORSA has a multimodal mechanism of action whereby it interrupts cell signaling pathways that cause replication and proliferation of cancer cells, re-establishes pathways for programmed cell death, or apoptosis, in cancer cells, and modulates the immune response against cancer cells.

Tagrisso is a registered trademark of AstraZeneca plc and is its top-selling drug with 2022 sales of more than $5 billion.

Genmab Announces Multiple Abstracts to be Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and European Hematology Association (EHA) Congress

On May 25, 2023 Genmab A/S (Nasdaq: GMAB) reported that multiple abstracts evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, will be presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, being held in Chicago, IL and virtually, June 2-6, 2023, and at the 2023 European Hematology Association (EHA) (Free EHA Whitepaper) Congress, being held in Frankfurt, Germany and virtually, June 8-11, 2023 (Press release, Genmab, MAY 25, 2023, View Source [SID1234632058]).

Presentations will include data from clinical trials evaluating the efficacy of epcoritamab in combination with standard-of-care therapies for the treatment of various types of B-cell non-Hodgkin lymphoma (NHL), including first-line, high-risk diffuse large B-cell lymphoma (DLBCL), relapsed or refractory large B-cell lymphoma (LBCL), and relapsed or refractory follicular lymphoma (FL). The safety and efficacy of epcoritamab has not been established for these investigational uses.

All abstracts accepted for presentation have been published and may be accessed online via the ASCO (Free ASCO Whitepaper) Meeting Library and EHA (Free EHA Whitepaper) Open Access Library.

"The data being presented this year at ASCO (Free ASCO Whitepaper) and EHA (Free EHA Whitepaper) demonstrate Genmab’s significant progress towards our mission to develop targeted antibody therapies with the goal of improving the lives of people impacted by hematologic malignancies," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "Together with AbbVie, we are committed to evaluating epcoritamab as a potential therapy for a variety of B-cell lymphomas through a robust clinical development program."

Genmab has also submitted abstracts evaluating epcoritamab, for potential presentation at the International Conference on Malignant Lymphoma, taking place June 13-17, 2023, in Lugano, Switzerland.

Abstracts accepted for presentation at ASCO (Free ASCO Whitepaper) include:

Epcoritamab:

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
7506 Epcoritamab + R2 regimen and responses in high-risk follicular lymphoma, regardless of POD24 status. R. W. Merryman, et al. Oral Tuesday, June 6, 2023, 11:45 AM CDT
7525 Effect of follow-up time on the ability of subcutaneous epcoritamab to induce deep and durable complete remissions in patients with relapsed/refractory large B-cell lymphoma: Updated results from the pivotal EPCORE NHL-1 trial; Y. Karimi, et al. Poster Monday, June 5, 2023, 08:00 AM – 11:00 AM CDT
7519 Metabolic response rates of epcoritamab + R-CHOP in patients with previously untreated (1L) high-risk diffuse large B-cell lymphoma, including double-hit/triple-hit lymphoma: Updated EPCORE NHL-2 data; L. Falchi, et al. Poster Discussion Monday, June 5, 2023, 1:15 PM CDT
7592 Phase 3 trial of subcutaneous epcoritamab + R-CHOP versus R-CHOP in patients (pts) with newly diagnosed diffuse large B-cell lymphoma (DLBCL): EPCORE DLBCL-2. L. Sehn, et al. Poster Monday, June 5, 2023, 08:00 AM – 11:00 AM CDT
e18919 Practice efficiency of treatment with epcoritamab versus glofitamab in relapsed/refractory diffuse large B-cell lymphoma. D. Huang, et al. Publication NA
Real-World Evidence:

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
7552 Real-world outcomes with novel therapies in R/R DLBCL. J. Crombie, et al. Poster Monday, June 5, 2023, 08:00 AM – 11:00 AM CDT
e19530 Racial and ethnic representation in large B-cell lymphoma trials and real-world databases. J. Munoz, et al. Publication NA
Abstracts accepted for presentation at EHA (Free EHA Whitepaper) include:

Epcoritamab:

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
S222 Epcoritamab with rituximab + lenalidomide (R2) provides durable responses in patients with high-risk follicular lymphoma, regardless of POD24 status. A. Sureda, et al. Oral Friday, June 9, 2023, 15:15 PM – 15:30 PM CEST
P1116 High complete metabolic response rates with epcoritamab + R-CHOP in previously untreated (1L) patients with high-risk diffuse large b-cell lymphoma, including double/triple-hit: EPCORE NHL-2 update. M. Clausen, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1118 Longer follow-up from the pivotal EPCORE NHL-1 trial reaffirms subcutaneous epcoritamab induces deep, durable complete remissions in patients with relapsed/refractory large B-cell lymphoma. W. Jurczak, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1149 Comparison of the efficacy of epcoritamab versus chimeric antigen receptor therapies, polatuzumab-based regimens, and tafasitamab-based regimens. A. Rosenthal, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1154 Efficacy of subcutaneous epcoritamab vs axi-cel in R/R DLBCL CAR T-naive and CAR T-eligible patients: an indirect comparison. G. Salles, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1169 Comparison of real-world clinical outcomes in patients with relapsed/refractory large B-cell lymphoma treated with epcoritamab vs chemoimmunotherapy. A. Mutebi, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
P1176 Clinical outcomes of novel therapies in relapsed/refractory diffuse large B-cell lymphoma. T. Wang, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
GEN3014 (HexaBody-CD38):

Abstract Number Abstract Title Type of Presentation Date/Time of Presentation
P816 Pharmacodynamic activity of GEN3014 (Hexabody-CD38) in patients with multiple myeloma supports enhanced complement dependent cytotoxicity of GEN3014 compared to daratumumab. I. Hiemstra, et al. Poster Friday, June 9, 2023, 6:00 PM – 7:00 PM CEST
About Epcoritamab
Epcoritamab-bysp 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 towards 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.i Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ oncology collaboration.

Epcoritamab was recently approved in the U.S. under the brand name EPKINLYTM and is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after 2 or more lines of systemic therapy.

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In October 2022, Genmab announced that AbbVie submitted a Marketing Authorization Application for epcoritamab for the treatment of patients with R/R DLBCL after two or more lines of systemic therapy, which was validated by the European Medicines Agency. Additionally, in December 2022, Genmab announced that the company submitted a Japan new drug application to the Ministry of Health, Labor and Welfare of Japan for epcoritamab for the treatment of patients with R/R LBCL after two or more lines of systemic therapy.

Genmab and AbbVie are continuing to evaluate the use of 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), an ongoing phase 3, open-label, randomized trial evaluating epcoritamab in combination in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R follicular lymphoma (FL) (NCT: 05409066). Please visit clinicaltrials.gov for more information.

U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNINGS

Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving EPKINLY (epcoritamab-bysp). Initiate treatment with the EPKINLY step-up dosing schedule to reduce the incidence and severity of CRS. Withhold EPKINLY until CRS resolves or permanently discontinue based on severity.
Immune effector cell–associated neurotoxicity syndrome (ICANS), including life-threatening and fatal reactions, can occur with EPKINLY. Monitor patients for neurological signs or symptoms of ICANS during treatment. Withhold EPKINLY until ICANS resolves or permanently discontinue based on severity.
Cytokine Release Syndrome (CRS)

EPKINLY can cause CRS, including serious or life-threatening reactions. CRS occurred in 51% of patients at the recommended dose in the clinical trial (37% grade 1, 17% grade 2, and 2.5% grade 3). Recurrent CRS occurred in 16% of patients. Of all the CRS events, most (92%) occurred during cycle 1. In cycle 1, 9% of CRS events occurred after the 0.16 mg dose (cycle 1, day 1), 16% after the 0.8 mg dose (cycle 1, day 8), 61% after the 48 mg dose (cycle 1, day 15), and 6% after the 48 mg dose (cycle 1, day 22). The median time to onset of CRS from the most recently administered EPKINLY dose across all doses was 24 hours (range, 0-10 days). The median time to onset after the first full 48 mg dose was 21 hours (range, 0-7 days). CRS resolved in 98% of patients; the median duration of CRS events was 2 days (range, 1-27 days).
Signs and symptoms of CRS can include pyrexia, hypotension, hypoxia, dyspnea, chills, and tachycardia. Concurrent neurological adverse reactions associated with CRS occurred in 2.5% of patients and included headache, confusional state, tremors, dizziness, and ataxia.
Initiate EPKINLY according to the step-up dosing schedule. Administer pretreatment medications to reduce the risk of CRS and monitor patients for potential CRS. Following administration of the first 48 mg dose, patients should be hospitalized for 24 hours. At the first signs or symptoms of CRS, immediately evaluate patients for hospitalization, manage per current practice guidelines, and administer supportive care as appropriate. Withhold or discontinue EPKINLY based on the severity of CRS.
Patients who experience CRS (or other adverse reactions that impair consciousness) should be evaluated and advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
Immune Effector Cell–Associated Neurotoxicity Syndrome (ICANS)

EPKINLY can cause life-threatening and fatal ICANS. ICANS occurred in 6% (10/157) of patients in the clinical trial (4.5% grade 1, 1.3% grade 2, 0.6% fatal: 1 event). Of the 10 ICANS events, 9 occurred in cycle 1 of treatment. The median time to onset was 16.5 days (range, 8-141 days) from the start of treatment. Relative to the most recent administration, the median time to onset was 3 days (range, 1-13 days). The median duration of ICANS was 4 days (range, 0-8 days), with ICANS resolving in 90% of patients with supportive care.
Signs and symptoms of ICANS can include confusional state, lethargy, tremors, dysgraphia, aphasia, and nonconvulsive status epilepticus. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor for potential ICANS. At the first signs or symptoms of ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or discontinue EPKINLY per recommendations and consider further management per current practice guidelines.
Patients who experience signs or symptoms of ICANS or any other adverse reactions that impair cognition or consciousness should be evaluated, including potential neurology evaluation, and patients at increased risk should be advised not to drive and to refrain from operating heavy or potentially dangerous machinery until resolution.
Infections

EPKINLY can cause serious and fatal infections. In the clinical trial, serious infections, including opportunistic infections, were reported in 15% of patients treated with EPKINLY at the recommended dose (14% grade 3 or 4, 1.3% fatal). The most common grade 3 or greater infections were sepsis, COVID-19, urinary tract infection, pneumonia, and upper respiratory tract infection.
Monitor patients for signs and symptoms of infection prior to and during treatment with EPKINLY and treat appropriately. Avoid administration of EPKINLY in patients with active infections.
Prior to starting EPKINLY, provide Pneumocystis jirovecii pneumonia (PJP) prophylaxis and consider prophylaxis against herpes virus.
Withhold or consider permanent discontinuation of EPKINLY based on severity.
Cytopenias

EPKINLY can cause serious or severe cytopenias, including neutropenia, anemia, and thrombocytopenia. Among patients who received the recommended dose in the clinical trial, grade 3 or 4 events occurred in 32% (decreased neutrophils), 12% (decreased hemoglobin), and 12% (decreased platelets). Febrile neutropenia occurred in 2.5%.
Monitor complete blood counts throughout treatment. Based on severity of cytopenias, temporarily withhold or permanently discontinue EPKINLY. Consider prophylactic granulocyte colony-stimulating factor administration as applicable.
Embryo-Fetal Toxicity

EPKINLY may cause fetal harm. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating EPKINLY. Advise females of reproductive potential to use effective contraception during treatment with EPKINLY and for 4 months after the last dose.

Adverse Reactions

The most common (≥20%) adverse reactions were CRS, fatigue, musculoskeletal pain, injection site reactions, pyrexia, abdominal pain, nausea, and diarrhea. The most common grade 3 to 4 laboratory abnormalities (≥10%) were decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

Lactation

Advise women not to breastfeed during treatment and for 4 months after the last dose of EPKINLY.

Please see the full Prescribing Information and Medication Guide, including Boxed Warnings.