On June 27, 2023 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage precision oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with genetically defined cancers, reported initial clinical data from the dose escalation portion of the Phase 1 clinical study of BDTX-1535 (Press release, Black Diamond Therapeutics, JUN 27, 2023, View Source [SID1234632928]). BDTX-1535 is an investigational fourth-generation epidermal growth factor receptor (EGFR) MasterKey inhibitor being developed for the treatment of non-small cell lung cancer (NSCLC) and glioblastoma multiforme (GBM). The new data from the dose escalation portion of the Phase 1 study demonstrated clinical proof of activity of BDTX-1535 in NSCLC patients harboring both acquired resistance and intrinsic driver EGFR mutations.

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"These initial safety and clinical activity data support the continued development of BDTX-1535 as a potential first and best-in-class treatment option for osimertinib-resistant NSCLC patients. Importantly, BDTX-1535 is the first EGFR TKI to show radiographic responses across NSCLC patients whose cancers are driven by diverse mutation families including acquired resistance mutations after osimertinib therapy, as well as in patients whose cancers are driven by classical and intrinsic driver mutations, providing clinical validation for our MasterKey approach of targeting families of mutations with a single drug," said Sergey Yurasov, M.D., Ph.D., Chief Medical Officer of Black Diamond Therapeutics. "With a favorable tolerability profile in dose escalation, a long half-life to support once-daily dosing and ease of administration, we believe that BDTX-1535 has the potential to become an important treatment option for patients suffering from EGFR-mutated NSCLC. With these data in hand, we look forward to working with the FDA to define our recommended Phase 2 dose selection strategy and, ultimately, discussing a path to potential accelerated approval in NSCLC patients with newly diagnosed and recurrent intrinsic and acquired resistance EGFR mutations."

"Intrinsic and acquired resistance to osimertinib remains a significant challenge for patients with EGFR-mutant lung cancers. There is a large unmet need to personalize therapies based on acquired EGFR resistance mechanisms post treatment with osimertinib but also an equally important unmet need to address intrinsic resistance, with a focus on EGFR mutation subtypes that do worse with current therapies such as EGFR L858R or atypical EGFR mutations such as EGFR exon 18 mutations. That is why a fourth-generation EGFR TKI that addresses intrinsic and acquired resistance by effectively targeting these EGFR alterations – combined with ease of administration and brain penetrance – may be an impactful treatment option for patients. I am eager to see BDTX-1535 continue to advance in the clinic," said Helena Yu, M.D., Associate Attending Physician at Memorial Sloan Kettering Cancer Center.

BDTX-1535 Phase 1 Study Design

This Phase 1 first-in-human, open-label clinical trial of BDTX-1535 consists of dose escalation followed by dose expansion cohorts. The dose escalation part is based on a Bayesian Optimal Interval adaptive design to evaluate the safety, pharmacokinetics (PK), and preliminary anti-tumor activity of BDTX-1535 in adult patients with either advanced/metastatic NSCLC harboring EGFR mutations with or without central nervous system (CNS) disease, or recurrent GBM expressing EGFR alterations. Following the dose escalation portion, the study includes several disease specific expansion cohorts to assess objective response rate (ORR), CNS ORR and progression-free survival and further evaluate safety, tolerability and PK.

Initial Phase 1 Dose Escalation Data

As of the data cutoff date of May 20, 2023, a total of 51 patients (24 patients with recurrent EGFR+ NSCLC and 27 patients with recurrent GBM with EGFR alterations) were treated with BDTX-1535 in the dose-escalation portion of the Phase 1 clinical trial at seven dose levels ranging from 15mg to 400mg once-daily (QD). NSCLC patients (n=24) were heavily pretreated with a median of two prior therapies (range 1-9); all patients received prior treatment with EGFR TKI with the majority receiving osimertinib (79%) as first- or second-line treatment, 67% of patients receiving prior chemotherapy, and 42% of patients receiving prior anti-angiogenesis drug or checkpoint inhibitors. All glioblastoma patients had a recurrent disease after standard of care surgery, radiation and chemotherapy. The Company will provide a clinical update on BDTX-1535 Phase 1 dose escalation data in recurrent GBM patients in the fourth quarter of 2023.

The BDTX-1535 PK profile obtained during dose escalation in NSCLC and GBM patients showed a linear increase in exposure with an average half-life of approximately 15 hours that supports a daily dosing schedule with sufficient and sustained steady state target mutation coverage achieved at 100 mg QD dose level and above.
BDTX-1535 was generally well tolerated by NSCLC and GBM patients and the overall safety profile was consistent with the EGFR tyrosine kinase inhibitor (TKI) class of drugs. The most common drug-related adverse events were mild to moderate rash, diarrhea, stomatitis, paronychia, nausea and fatigue. No patients experienced dose limiting toxicity at 15-200 mg QD doses. One of 15 patients treated at the 300 mg QD dose experienced dose limiting diarrhea and 5 of 12 patients at the 400 mg QD dose experienced dose limiting toxicity (diarrhea, 2 patients; rash, stomatitis, fatigue and decreased appetite, 1 patient each). No unexpected safety signal was identified during dose escalation.
Based on additional data updates as of June 16, 2023, 5 of 12 NSCLC patients in a subgroup, who had measurable disease at study start, and underwent post baseline tumor assessment by RECIST1.1, demonstrated radiographic confirmed partial response (PR). One additional patient demonstrated unconfirmed PR awaiting confirmation, while the remaining six patients had stable disease.
Confirmed PRs were observed in NSCLC patients with a wide range of EGFR mutations including classical and intrinsic driver mutations and acquired C797S resistance mutation, as well as complex mutations that include a combination of classical, intrinsic, and acquired resistance mutations. Radiographic improvement of CNS metastasis was documented in 2 NSCLC patients.
Based on emerging PK, safety, tolerability and radiographic response data, enrollment will commence at the BDTX-1535 200 mg QD dose in two expansion cohorts of NSCLC patients with acquired resistance or intrinsic driver mutations who received up to two prior lines of therapy including a third-generation EGFR TKI. Additional doses may be further evaluated after review of the totality of dose escalation data during a meeting with the U.S. Food and Drug Administration (FDA) later in 2023. The objective of expansion cohorts will be ORR by RECIST 1.1 and durability of response to support future discussion with the FDA of a potential accelerated approval path in EGFR-mutated NSCLC. In addition, BDTX plans to open an expansion cohort in newly diagnosed NSCLC patients with intrinsic driver mutations after discussion with the FDA.
Black Diamond anticipates the following key milestones for BDTX-1535:

Initiation of the dose expansion cohorts of NSCLC patients with EGFR acquired resistance and intrinsic driver mutations after progression on third generation EGFR TKI with the objective of ORR by RECIST 1.1 in the second half of 2023
Presentation of the full BDTX-1535 dose escalation data in NSCLC at a medical conference in the fourth quarter of 2023
Meeting with the FDA in the fourth quarter of 2023 to align on dosing strategy to enable a potential accelerated approval pathway in NSCLC
Initiation of an expansion cohort in newly diagnosed NSCLC patients with intrinsic driver mutations after discussion with the FDA
Clinical update on BDTX-1535 Phase 1 dose escalation data in recurrent GBM patients in the fourth quarter of 2023
Conference Call Information

Black Diamond will host a conference call and webcast on Tuesday, June 27, 2023, at 8:00 a.m. ET to discuss the initial results from the Phase 1 dose escalation study of BDTX-1535 in patients with NSCLC. The webcast may be accessed online here or by visiting the Events page in the Investors section of the Company’s website at www.blackdiamondtherapeutics.com.

A replay of the webcast will be available for 30 days on the Investors section of Black Diamond’s website.

On June 27, 2023 Biodesix, Inc. (Nasdaq: BDSX), a leading data-driven diagnostic solutions company with a focus in lung disease, reported that the large multi-center observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) has completed enrollment of 5,000 patients with non-small cell lung cancer (NSCLC) (Press release, Biodesix, JUN 27, 2023, View Source [SID1234632927]). The study was designed to further validate the utility of the VeriStrat test, a novel predictive and prognostic blood-based host immune classifier, and its ability to support treatment decisions for patients with NSCLC across different therapeutic approaches.

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"The INSIGHT study gives us a unique opportunity to examine real world treatment patterns for lung cancer, the deadliest of all cancers, in the context of patients’ immune response," said Dr. James Jett, co-Chief Medical Officer at Biodesix. "Five-year survival for patients with non-small cell lung cancer is approximately 25 percent, but now we are seeing that with use of this proteomic test, we are able to identify treatment options, particularly those utilizing Immune Checkpoint Inhibitors in addition to standard chemotherapy, that may extend overall survival in select groups of patients."

Results from prior analyses of the INSIGHT study demonstrated that the VeriStrat test stratifies immune checkpoint inhibition (ICI) treatment response in patients with advanced NSCLC. This data demonstrated that those classified as Host Immune Classifier Cold (HIC-C), also known as VeriStrat Poor, had superior median overall survival when receiving ICI plus chemotherapy versus ICI alone, independent of PD-L1 status.

A recent analysis from this study has been accepted for presentation at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer in Singapore in September 2023. Future analyses of the INSIGHT study are planned in 2024, as monitoring of patient outcomes continues.

On June 27, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of its TLR-3 agonist Ampligen (rintatolimod) as a novel and potentially powerful therapeutic in locally advanced pancreatic cancer ("LAPC") and metastatic pancreatic cancer, reported the required approvals from the Netherlands for Erasmus Medical Center ("Erasmus MC") to begin a Phase 1b/2 study under the previously announced external sponsored collaborative clinical research agreement with AstraZeneca and Erasmus MC (Press release, AIM ImmunoTech, JUN 27, 2023, View Source [SID1234632925]).

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The authorizations are from the Central Committee on Research Involving Human Subjects, which is the Competent Authority for the review of clinical trials in the Netherlands, and the Medical Ethics Review Committee Erasmus MC, which is the governing ethics board.

The investigator-initiated clinical study, entitled "Combining anti-PD-L1 immune checkpoint inhibitor durvalumab with TLR-3 agonist rintatolimod in patients with metastatic pancreatic ductal adenocarcinoma for therapy effect" (the "DURIPANC Study"), is an exploratory, open-label, single center, Phase 1b/2 study which will use Study Drugs provided by AstraZeneca and AIM ImmunoTech. The primary objective of the Phase 1b portion of the study is to determine the safety of combination therapy with durvalumab and Ampligen. The primary objective of the Phase 2 portion of the trial is to determine the clinical benefit rate of combination therapy with durvalumab and Ampligen.

"We continue to successfully advance the synergistic potential of Ampligen with checkpoint blockade therapeutics. The DURIPANC Study is an important step forward in our strategic development plan. This plan expands the reach of Ampligen with another type of checkpoint blockade therapy we believe to be ideally suited for the treatment of pancreatic cancer," commented AIM Chief Executive Officer Thomas K. Equels.

Prof. Casper H.J. van Eijck, MD, PhD, Pancreato-biliary Surgeon at Erasmus MC, added, "With this authorization now in hand, we are working to get the clinical study up and enrolling patients as quickly as possible. At Erasmus MC, we see the promise of combining Ampligen with durvalumab and believe this approach has the potential for synergistic anti-tumor activity."

The DURIPANC Study is expected to enroll between 9 and 18 subjects in the Phase 1b portion and between 13 and 25 patients in the Phase 2 portion of the study. All included patients will receive combination therapy with Ampligen and durvalumab. Patients will start with Ampligen 200mg via IV infusion twice per week for a total of 6 weeks (12 doses). Ampligen dose will be escalated to 400mg according to a 3+3 DLT design. The first dose of Ampligen will be administered preferably 4-6 weeks after the last chemotherapy FOLFIRINOX dose. After two doses of Ampligen, the first dose of durvalumab 1500mg via IV infusion will be introduced in week 2. Patients will continue to receive 1500 mg durvalumab via IV infusion every 4 weeks for up to a maximum of 48 weeks (up to 12 doses/cycles) with the last administration on week 48 or until confirmed disease progression according to Response Evaluation Criteria in solid Tumors (RECIST 1.1), unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

On June 27, 2023 AIM ImmunoTech Inc. (NYSE American: AIM) ("AIM" or the "Company"), an immuno-pharma company focused on the research and development of its TLR-3 agonist Ampligen (rintatolimod) as a novel and potentially powerful therapeutic in locally advanced pancreatic cancer ("LAPC") and metastatic pancreatic cancer, reported the publication of pre-clinical data that suggests Ampligen has the potential to act directly on tumor cells to reduce tumor cell growth in pancreatic cancer patients with sufficient tumor levels of TLR-3, suggesting a potential biomarker to identify patients who may respond to Ampligen (Press release, AIM ImmunoTech, JUN 27, 2023, View Source [SID1234632924]). The anti-tumor analysis was published in the peer-reviewed journal American Journal of Cancer Research in the paper "Rintatolimod: A potential treatment in patients with pancreatic cancer expressing Toll-like receptor 3."

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Ampligen is a dsRNA product candidate that acts via the TLR-3 receptor present on several immune cells, epithelial cells and tumors. Researchers at the Erasmus University Medical Center ("Erasmus MC") evaluated TLR-3 protein and mRNA expression in thirteen pancreatic ductal adenocarcinoma (PDAC) tissue samples as well as in the human PDAC (hPDAC) cell lines CFPAC-1, MIAPaCa-2 and PANC-1 using immunohistochemistry and multiplexed gene expression analysis. The direct anti-tumor effects of Ampligen were investigated using proliferation and migration assays after different incubation time points with increasing concentrations of Ampligen (ranging from 0.05 to 0.4 mg/ml).

After treating these three cell lines with Ampligen, researchers observed significantly lower cell numbers (amount of DNA per well, representing proliferation) and lower migration rates only in the high TLR-3 expressing CFPAC-1 cells, suggesting that the variating TLR-3 abundance of the three hPDAC cell lines influences the effect of Ampligen on cell proliferation and cell migration.

Prof. Casper H.J. van Eijck, MD, PhD, Pancreato-biliary Surgeon at Erasmus MC and co-author of the published paper, states: "An immune-modulating TLR-3 agonist such as Ampligen is considered a promising novel treatment option for pancreatic cancer and might have additional anti-tumoral effects on epithelial tumor cells expressing TLR-3. Based on our findings, we believe Ampligen is likely an agent offering anti-tumor effects and potentially meeting the critical need for more effective therapies to treat pancreatic cancer."

AIM has a diverse clinical and business portfolio concerning the treatment of pancreatic cancer:

The AMP-270 Phase 2 clinical trial is a randomized, open-label, controlled, parallel-arm study with the primary objective of comparing the efficacy of Ampligen versus a no treatment control group following FOLFIRINOX for subjects with locally advanced pancreatic adenocarcinoma. Secondary objectives include comparing safety and tolerability. (ClinicalTrials.gov: NCT05494697)
AIM entered into an external sponsored collaborative clinical research agreement to support a clinical trial at Erasmus MC combining AstraZeneca’s anti-PD-L1 immune checkpoint inhibitor durvalumab with Ampligen in patients with metastatic pancreatic ductal adenocarcinoma. The study launch is expected in Q4 2023.
In March 2021, AIM was granted a patent by the Netherlands Patent Office with granted patent claims that include, but are not limited to, the use of Ampligen as a combination cancer therapy with checkpoint blockade inhibitors (e.g., pembrolizumab, durvalumab).
AIM has been granted U.S. Food and Drug Administration orphan drug designation status and European Medicines Agency orphan medicinal product designation status for Ampligen in the treatment of pancreatic cancer.
AIM CEO Thomas K. Equels states: "We remain committed to establishing a new standard of care for pancreatic cancer where there remains a significant unmet need. The data generated to date, including the findings from this pre-clinical study, continue to bolster our confidence in the potential of Ampligen for the treatment of pancreatic cancer. These positive results provide further validation as we continue to focus on advancing our pancreatic cancer development program and execute on our path forward."

On June 27, 2023 AbbVie (NYSE: ABBV) and Genmab (Nasdaq: GMAB) reported topline results from the follicular lymphoma (FL) cohort of the Phase 1/2 EPCORE NHL-1 clinical trial evaluating epcoritamab (DuoBody-CD3xCD20), an investigational T-cell engaging bispecific antibody administered subcutaneously (Press release, AbbVie, JUN 27, 2023, View Source [SID1234632923]). The study cohort includes 128 adult patients with relapsed or refractory (R/R) FL who received at least two or more lines of systemic therapy. 70.3 percent of patients were double refractory to an anti-CD20 monoclonal antibody and an alkylating agent. Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies’ oncology collaboration.

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"We are encouraged by these topline results, which further support the clinical profile of epcoritamab as a potential therapeutic option for patients with relapsed or refractory follicular lymphoma," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "Together with our partner Genmab, these results may bring us one step closer to our goal of advancing a potential core therapy for patients with B-cell malignancies."

EPCORE NHL-1 is an open-label trial evaluating the safety and preliminary efficacy of epcoritamab and consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a optimization part. The topline results from this cohort showed an overall response rate (ORR) of 82 percent as confirmed by an independent review committee (IRC), which exceeded the protocol prespecified threshold for efficacy. The observed median duration of response (DOR) was not reached, and longer follow-up will be required. The median number of lines of prior therapy in this cohort was three (range: two to four lines of therapy).

No new safety signals were observed with epcoritamab in this study at the time of this analysis. The most common treatment-emergent adverse event was cytokine release syndrome (CRS) with 66.4 percent (1.6 percent Grade 3 or higher). The optimization part of the trial is continuing to evaluate alternative step-up dosing regimens to help further mitigate the risk of CRS, preliminary data are encouraging.

Full results from the study will be submitted for presentation at a future medical meeting.

About the Phase 1/2 EPCORE NHL-1 trial
EPCORE NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin’s lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a expansion part, additional patients are being enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed or refractory (R/R) B-cell NHLs who have limited therapeutic options. The dose optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 CRS and mitigate Grade ≥3 cytokine release syndrome. The primary endpoint of the expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were evaluated as secondary efficacy endpoints.

About Follicular Lymphoma
Follicular lymphoma (FL) is typically an indolent, or slow growing, form of NHL that arises from B-cell lymphocytes.1 FL is the second most common form of NHL overall, accounting for 20 to 30 percent of all NHL cases, and representing 10 to 20 percent of all lymphomas in the western world.2,3 Although FL is an indolent lymphoma, it is considered incurable with conventional therapy.4,5

About Epcoritamab
Epcoritamab is an investigational 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.6

Epcoritamab-bysp (EPKINLY) was recently approved in the United States (U.S.) and is indicated for the treatment of adult patients with R/R diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two 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). Please see U.S. Important Safety Information below.

In October 2022, a Marketing Authorization Application was submitted 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, a Japan new drug application was submitted to the Ministry of Health, Labor and Welfare of Japan for epcoritamab for the treatment of patients with R/R large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Epcoritamab is not approved in the European Union and Japan.

The companies will share commercial responsibilities in the United States and Japan, with AbbVie responsible for further global commercialization. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets excluding the United States and Japan throughout the year.

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 FL (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.

EPKINLY (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop symptoms of CRS, including fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, trouble breathing, chills, fast heartbeat, feeling anxious, headache, confusion, shaking (tremors), or problems with balance and movement, such as trouble walking.

Due to the risk of CRS, you will receive EPKINLY on a "step-up" dosing schedule. The step-up dosing schedule is when you receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of your first cycle of treatment (cycle 1). You will receive your first full dose of EPKINLY on day 15 of cycle 1. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule. Before each dose in cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.

Neurologic problems. EPKINLY can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any symptoms of neurologic problems, including trouble speaking or writing, confusion and disorientation, drowsiness, tiredness or lack of energy, muscle weakness, shaking (tremors), seizures, or memory loss.
Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will monitor you for symptoms of CRS and neurologic problems during treatment with EPKINLY, as well as other side effects, and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with EPKINLY if you develop CRS, neurologic problems, or any other side effects that are severe.

Do not drive or use heavy or potentially dangerous machinery if you develop dizziness, confusion, tremors, drowsiness, or any other symptoms that impair consciousness until your symptoms go away. These may be symptoms of CRS or neurologic problems.

EPKINLY can also cause other serious side effects, including:

Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for symptoms of infection before and during treatment. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
Low blood cell counts. Low blood cell counts are common during treatment with EPKINLY and can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cell counts (neutropenia), which can increase your risk for infection; low red blood cell counts (anemia), which can cause tiredness and shortness of breath; and low platelet counts (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. EPKINLY may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with EPKINLY. You should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY.
are breastfeeding or plan to breastfeed. It is not known if EPKINLY passes into your breast milk. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea.

These are not all the possible side effects of EPKINLY. Call your doctor for medical advice about side effects.

You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see the Full Prescribing Information and Medication Guide, including Important Warnings.