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Vincerx Pharma Presents Data on PTEFb/CDK9 Inhibitor VIP152 in DLBCL and CLL at the 63rd American Society of Hematology Annual Meeting

On December 11, 2021 Vincerx Pharma, Inc. (Nasdaq: VINC) a biopharmaceutical company aspiring to address the unmet medical needs of patients with cancer through paradigm-shifting therapeutics, reported data on VIP152, the Company’s PTEFb/CDK9 inhibitor, in high-grade B-cell lymphoma (HGBL), formerly referred to as double-hit lymphoma (DHL), and chronic lymphocytic leukemia (CLL), in two presentations at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held December 11-14, 2021 in Atlanta GA (Press release, Vincerx Pharma, DEC 11, 2021, View Source [SID1234596816]).

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"The data presented at ASH (Free ASH Whitepaper) show that VIP152 has increased selectivity and potency as compared with other CDK9 inhibitors in development across high-grade B cell lymphoma and chronic lymphocytic leukemia models of disease," said Ahmed Hamdy M.D., Chief Executive Officer of Vincerx, "The consistency of preclinical data are noteworthy, with robust effects on key biomarkers of CDK9 inhibition including the durable downregulation of RNA polymerase II as well as the sustained reduction, and near clearance of, MYC and MCL-1 mRNA and protein. These results also translate through to primary samples from patients, with VIP152 demonstrating cytotoxic activity that overcomes stromal protection in primary CLL samples, and pharmacodynamic effects on key transcriptional targets observed in blood of patients with HGBL treated with VIP152. These results suggest that the demonstrated effects of VIP152 may translate to the clinic to provide new treatment options for patients with MYC and MCL-1- driven malignancies. With these expanded mechanism data in hand, we are currently enrolling two studies, a Phase 1b expansion study in relapsed/refractory aggressive lymphoma and advanced solid tumors, and a Phase 1b dose-escalation in CLL relapsed/refractory to venetoclax and BTK inhibitors."

Key Presentation Highlights:

Poster presentation, titled, "VIP152, a selective CDK9 inhibitor, induces complete regression of high-grade B-cell lymphoma (HGBL) models and depletion of short-lived oncogenic driver transcripts, MYC and MCL1, with a once weekly schedule" presented by Melanie Frigault, Ph.D., Vice President of Translational Medicine, Vincerx, include:

Compared with two oral CDK9 inhibitors in development, KB-0742 and atuveciclib, at equimolar concentrations, VIP152 demonstrated more potent and durable downregulation of phospho-Serine 2 on RNA polymerase II, a key biomarker for evaluating the mechanism of action of CDK9 inhibitors (50% reduction for 24–48 hours). Additionally, depletion of short half-life MYC and MCL-1 transcript levels up to 48 hours was observed.
VIP152 treatment conferred a shift in transcriptional program, supporting an oncogenic shock mechanism of action, and sustained robust reduction and near clearance of MYC and MCL-1 proteins in MYC overexpressing lymphoma cell lines.
Once weekly VIP152 treatment showed antitumor efficacy as demonstrated by dose-dependent tumor regression and tumor-outgrowth control in the SU-DHL-10 (a MYC overexpressing cell line) xenograft model.
The pharmacodynamic effect demonstrated in the blood of HGBL patients treated with VIP152 suggests that the effect may translate to the clinic. Tumor-based pharmacodynamic studies are planned to confirm these findings.
VIP152 is currently being evaluated in HGBL patients and other MYC expressing indications in the clinic (ClinicalTrials.gov Identifier: NCT02635672).
Oral presentation titled, "VIP152 Is a Novel CDK9 Inhibitor with Efficacy in Chronic Lymphocytic Leukemia" presented by Steven Sher, The Ohio State University Comprehensive Cancer Center, include:

VIP152 shows selective CDK9 inhibition with improved activity over other CDK9 inhibitors in development including dinaciclib, KB-0742 and atuveciclib.
VIP152 induces apoptosis in CLL cell lines and demonstrates cytotoxic activity that overcomes stromal protection of primary CLL samples.
VIP152 disrupts transcriptomics of patient samples after a two-hour treatment, alters cellular programming and disrupts binding of CDK9 to canonical binding partners, thereby inhibiting its function.
VIP152 weekly dosing decreases peripheral disease in a circulating tumor CLL mouse model and improves survival.
Data support the ongoing clinical trial in CLL (ClinicalTrials.gov Identifier: NCT04978779).
Vincerx will be hosting a KOL webinar today, at 7:30pm Eastern Standard Time. The webinar will feature presentations from KOLs John C. Byrd, M.D. (University of Cincinnati) and Rosa Lapalombella, Ph.D. (The Ohio State University) who will discuss the current treatment landscape and unmet medical need in treating patients suffering from CLL and the VIP152 data presented earlier that day at the ASH (Free ASH Whitepaper) Annual Meeting. Vincerx Pharma’s Vice President of Translational Medicine, Melanie Frigault, Ph.D., will also discuss the VIP152 mechanism of action in lymphoma poster presented at ASH (Free ASH Whitepaper)

A live Q&A session will follow the formal presentations. To register for the webinar, please click here.

The poster can be accessed on the presentations section of the Vincerx website.

IGM Biosciences Presents Clinical Data from IGM-2323 in Patients with Advanced B Cell Malignancies at 2021 American Society of Hematology Annual Meeting

On December 11, 2021 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company focused on creating and developing engineered IgM antibodies, reported the presentation of clinical results from the Company’s Phase 1 trial evaluating IGM-2323, a novel bispecific IgM antibody targeting CD20 x CD3, at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (Press release, IGM Biosciences, DEC 11, 2021, View Source [SID1234596814]). The data was featured today in an oral presentation titled "A Phase 1 Dose Escalation Study of IGM-2323, a Novel Anti-CD20 x Anti-CD3 IgM T Cell Engager (TCE) in Patients with Advanced B-Cell Malignancies".

The multicenter, open-label Phase 1 dose escalation trial was intended to assess the safety, pharmacokinetics and preliminary efficacy of intravenous IGM-2323 in patients with advanced B cell malignancies. As of September 10, 2021, the data cutoff date for the presentation, 40 patients were enrolled and treated at escalating dose levels of IGM-2323.

All 40 patients received at least one dose and were evaluable for safety. There were no dose limiting toxicities (DLTs), no neurotoxicity adverse events (AEs), a relatively low rate of cytokine release syndrome (CRS) and no patients discontinued due to an AE.

Of the 10 patients treated in the 100 mg cohort, 3 of 6 diffuse large B cell lymphoma (DLBCL) patients had a complete response and 2 of 3 follicular lymphoma (FL) patients had a complete response. Additionally, the one mantle cell patient treated in the 100 mg dose cohort had a partial response. Overall, of the 38 patients evaluable for efficacy, 11 patients showed a response, 8 of which were complete responses.

Based on these promising results, two Phase 2 studies are being initiated to assess the safety and efficacy of two doses of IGM-2323, 100 mg and 300 mg, in patients with DLBCL and FL. If supportive, the data from this Phase 2 multicenter, open-label study could potentially be used as the basis for accelerated review and approval of IGM-2323.

"Data presented today demonstrate that IGM-2323 is highly active against multiple subtypes of relapsed/ refractory non-Hodgkin’s lymphoma and shows an excellent safety profile with low rates of CRS, no CRS-associated neurotoxicity and minimal neutropenia," said Dr. Elizabeth Budde, M.D., Ph.D., Assistant Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center. "Results to date from this Phase 1 study are encouraging, and I look forward to continuing to investigate this important novel therapy’s potential in these difficult-to-treat disease areas. Patients with non-Hodgkin’s lymphoma need efficacious and well-tolerated treatments, and IGM-2323 is potentially well-suited to help with this unmet need."

"We are pleased to show multiple complete responses in patients with diffuse large B cell lymphoma and follicular lymphoma at the 100 mg dose level and encouraging, consistent safety data," said Chris Takimoto, M.D., Ph.D., F.A.C.P., Chief Medical Officer of IGM Biosciences. "We are excited to continue the development of IGM-2323 by moving forward with our Phase 2 expansion studies and by initiating combination studies in earlier lines of treatment. We believe these clinical results are also encouraging for the development of the IgM T cell engagers targeting CD38 and CD123 in our hematologic pipeline."

Conference Call and Webcast
The conference call may be accessed by dialing (866) 649-1996 (domestic) or (409) 217-8769 (international) and referring to conference ID 9695193. A live webcast of the presentation will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at View Source A replay of the webcast will be archived on the Company’s website for 90 days following the presentation.

About IGM-2323
IGM-2323 is a CD20 x CD3 bispecific IgM antibody designed to treat patients with B cell non-Hodgkin’s lymphoma (NHL) and other B cell malignancies. CD20 is a protein that is frequently expressed on the surface of malignant B cells, while CD3 is a protein that is expressed on the surface of T cells and is an essential activating molecule of the T cell. IGM-2323 has 10 binding domains to CD20 and a single binding domain to CD3 (specifically CD3ɛ).

IGM-2323 is designed to simultaneously and stably bind a CD20 expressing cancer cell as well as CD3 on a cytotoxic T cell, bringing both cells into close proximity. This interaction mimics the normal T cell activation pathway leading the T cell to recognize and kill the cancer cell by releasing cytotoxic biochemicals (perforins and granzymes) that penetrate and perforate the cancer cell. In contrast to other bispecific antibody formats that bind to one or two CD20 molecules on the surface of the cancer cell and to one CD3 molecule on the surface of the T cell, IGM-2323 has 10 binding units to CD20 and one binding unit to CD3. The Company believes that IGM-2323 with its 10 binding units for CD20 may successfully bind to CD20 expressing cancer cells with more avidity compared to an IgG bispecific antibody with only one binding unit for CD20.

IGM-2323 also employs an additional mechanism to kill CD20 expressing cancer cells, known as complement dependent cytotoxicity (CDC). CDC is a mechanism by which antibodies can mediate specific targeted cell killing by activating the complement system. Components of the complement system are naturally present in humans, and IgM antibodies are the most efficient antibodies at engaging the complement system for CDC, with an approximately 100-fold increase in CDC relative to comparable IgG CD20 antibodies.

Imago BioSciences Presents Positive Data from Ongoing Phase 2 Study of Bomedemstat in Advanced Myelofibrosis at ASH 2021

On December 11, 2021 Imago BioSciences, Inc. ("Imago") (Nasdaq: IMGO), a clinical stage biopharmaceutical company discovering new medicines for the treatment of myeloproliferative neoplasms (MPNs), today presented positive data from its ongoing global Phase 2 clinical study evaluating bomedemstat in patients with advanced myelofibrosis (MF) (Press release, Imago BioSciences, DEC 11, 2021, View Source [SID1234596813]). The data were presented in an oral session during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place December 11-14, 2021. Previously, a Phase 2 data set with a cut-off date of May 17, 2021 was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress.

Updated Highlights (as of November 1, 2021 cutoff):

Of the evaluable patients at 24 weeks:
74% (17/23) showed a decrease in Total Symptom Score (TSS).
26% (6/23) showed a ≥50% decrease in TSS.
75% (30/40) showed spleen volume reductions.
81% (103/127) of mutant allele frequencies (MAFs) were either stable (45%) or reduced (36%), including driver and high molecular risk (HMR) mutations such as ASXL1.
89% (32/36) of patients who were transfusion-independent at baseline had stable or improved hemoglobin at 12 weeks.
No new mutations or transformation to acute myeloid leukemia (AML) in more than 600 days of follow-up in patients with high risk of progression.
"Today’s ASH (Free ASH Whitepaper) 2021 data further demonstrates the potential of bomedemstat as a unique and differentiated treatment option for patients living with advanced myelofibrosis," said Wan-Jen Hong, M.D., CMO, Imago BioSciences. "We were gratified to reach full enrollment in our myelofibrosis trial earlier this year and remain pleased with the safety and tolerability profile observed to date. Looking ahead, we anticipate continued momentum in this program through an investigator-sponsored trial evaluating bomedemstat in combination with ruxolitinib in MF patients who are either treatment naïve or respond sub-optimally to ruxolitinib treatment."

Safety & Tolerability

Bomedemstat was generally well-tolerated to date in patients with myelofibrosis.
The most common non-hematologic AE related to bomedemstat was dysgeusia (altered taste), which occurred in 27 patients (30%).
"Bomedemstat continues to show strong potential as a monotherapy that may offer distinct clinical benefits for patients living with advanced myelofibrosis," said Hugh Y. Rienhoff, Jr., M.D., CEO, Imago BioSciences. "A large majority of the patients enrolled in this trial saw improvements in symptom scores, spleen volumes and occurrence of anemia. Altogether, these data show that bomedemstat may have a significant impact on this progressive and often debilitating disease."

Details on Imago’s ASH (Free ASH Whitepaper) Presentation

Oral Presentation Title: A Phase 2 Study of the LSD1 Inhibitor IMG-7289 (Bomedemstat) for the Treatment of Advanced Myelofibrosis
Session: Myeloproliferative Syndromes: Clinical and Epidemiological: Novel Therapies for MPNs and JAK inhibitors for Myelofibrosis
Presenter: Harinder Gill, M.D., study investigator and presenter of the data, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
Date and Time: December 11, 2021, at 12:00 PM ET

For further details, please see the ASH (Free ASH Whitepaper) 2021 abstract and presentation on the Imago website here.

About Imago’s Phase 2 Advanced Myelofibrosis Program

Myelofibrosis (MF) is a progressive cancer in which the bone marrow is gradually replaced by fibrous, scar-like tissue. There is a significant unmet need for a disease-modifying therapy. The need is greatest in patients with MF whose disease is not adequately managed with current JAK inhibitors, the current standard of care.

This Phase 2b multi-center, open-label study is designed to assess the safety, efficacy, pharmacodynamics, and spleen volume reduction of bomedemstat, an oral inhibitor of the lysine-specific demethylase 1 (LSD1). Eligible patients aged 18 or over with MF who are refractory or resistant to, intolerant of, are inadequately controlled by or ineligible for approved therapies were considered for the study. Exploratory assessments include symptom reduction, changes in cytokine profiles, changes in the frequency of mutant alleles and bone marrow fibrosis. The trial is being conducted in the United States, United Kingdom, European Union and Hong Kong. This ongoing 24-week study completed enrollment in May 2021 for a total of 89 patients.

MorphoSys and Incyte Announce Additional Real-World Evidence Results from RE-MIND2 Study of Tafasitamab (Monjuvi®) in Combination with Lenalidomide for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma

On December 11, 2021 MorphoSys US Inc., a fully owned subsidiary of MorphoSys AG (FSE: MOR; NASDAQ: MOR), and Incyte (NASDAQ:INCY) reported additional real-world evidence results from the RE-MIND2 study comparing tafasitamab (Monjuvi) in combination with lenalidomide against the most frequently used treatments in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (Press release, Incyte, DEC 11, 2021, View Source [SID1234596812]). These treatments include polatuzumab vedotin plus bendamustine and rituximab (Pola-BR), rituximab plus lenalidomide (R2), and CD19 chimeric antigen receptor T-cell (CAR-T) therapies. The data, which builds on the primary analysis presented at the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO 2021), will be presented as an oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition (ASH 2021), held December 11-14, 2021 in Atlanta, Georgia and virtually.

"In this retrospective cohort analysis, a statistically significant OS difference was observed, favoring tafasitamab plus lenalidomide over pola-BR and R2 in patients with relapsed or refractory DLBCL who are ineligible for transplant – a traditionally difficult-to-treat population," said Grzegorz Nowakowski, M.D., Professor of Medicine and Oncology at the Mayo Clinic, and lead investigator for the RE-MIND2 study*. "I am encouraged by the OS difference favoring tafasitamab plus lenalidomide and the comparable OS between tafasitamab and lenalidomide and CAR-T, specifically the potential prolonged survival benefit the tafasitamab plus lenalidomide combination may offer my patients."

Findings from the RE-MIND2 study presented at ASH (Free ASH Whitepaper) 2021 indicated that tafasitamab plus lenalidomide resulted in statistically significant differences across several endpoints. Specifically, results showed:

The primary endpoint, overall survival (OS), was met with significant improvement observed for tafasitamab plus lenalidomide at 20.1 months compared to Pola-BR at 7.2 months (p=0.038), and 24.6 months for tafasitamab plus lenalidomide compared to 7.4 months for R2 (p=0.014).
A comparable median OS benefit was observed with tafasitamab plus lenalidomide at 22.5 months compared to CAR-T at 15 months without statistical significance.
Objective response rate (ORR), a key secondary endpoint, was observed with statistical significance for tafasitamab plus lenalidomide at 63.6% versus R2 at 30.3% (p=0.013).
Tafasitamab plus lenalidomide also achieved significantly higher complete response rate (CR), a key secondary endpoint, at 39.4% versus 15.2% for R2 (p=0.0514).
While safety endpoints were not included in this study, the most common adverse events (AEs) associated with tafasitamab plus lenalidomide are feeling tired or weak, diarrhea, cough, fever, swelling of lower legs or hands, respiratory tract infection and decreased appetite.
Of 3,454 patients enrolled from 200 sites, 106, 106 and 149 patients were treated with pol-BR, R2 and CAR-T, respectively. For the comparative analysis, matched patient pairs were created using 1:1 nearest neighbor matching with a caliper. Matched pairs consisted of: tafasitamab + len vs pol-BR, n=24 pairs; vs R2, n=33; and vs CAR-T, n=37 pairs.

"The RE-MIND 2 Study is an example of our continued commitment to generating practice relevant real-world evidence which, in general, more realistically captures the clinical heterogeneity in cancer and allows us expanded opportunities to dynamically assess the patient experience. These data indicate that tafasitamab plus lenalidomide is a meaningful option for patients and has the potential to become a future backbone therapy in DLBCL," said Nuwan Kurukulasuriya, Ph.D., Senior Vice President, Global Head of Medical Affairs, MorphoSys.

"We are pleased to see the survival benefit for patients with relapsed or refractory DLBCL in the data from the RE-MIND2 study," said Peter Langmuir, M.D., Group Vice President, Oncology Targeted Therapies, Incyte. "As we continue to establish tafasitamab in combination with lenalidomide as the standard of care in second-line treatment for DLBCL, we look forward to exploring the body of clinical evidence and bringing this novel treatment to patients with DLBCL and potentially even to other indications."

Presentations are available on the ASH (Free ASH Whitepaper) website at View Source; #183 (oral presentation).

In July 2020, the U.S. Food and Drug Administration (FDA) approved Monjuvi (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for ASCT. This indication is approved under accelerated approval based on ORR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). The U.S. approval is based on an efficacy subgroup of 71 patients confirmed by central lab. The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide1, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about 40% of patients not responding to initial therapy or relapsing thereafter2, leading to a high medical need for new, effective therapies3, especially for patients who are not eligible for an autologous stem cell transplant in this setting.

About RE-MIND2

The RE-MIND2 study is an observational, retrospective cohort study (NCT04697160) that compares outcomes with those from the L-MIND study for autologous stem cell transplant (ASCT)-ineligible patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), who are treated with therapies recommended by the National Comprehensive Cancer Network/European Society for Medical Oncology (NCCN/ESMO). The study utilized real-world data to generate external comparators for patients in the L-MIND trial. The primary analysis of the study compared patient outcomes from L-MIND with matched patient populations treated with gemcitabine-oxaliplatin plus rituximab (R-GemOx), bendamustine and rituximab (BR) and pooled systemic NCCN/ESMO recommended therapies. The additional analysis evaluated tafasitamab in combination with lenalidomide versus Pola-BR, R2 and CAR-T therapies. Patients enrolled in the study were aged 18 years or older with histologically confirmed DLBCL and had received two or more systemic therapies for DLBCL, including one or more anti-CD20 therapy. The study’s primary endpoint is overall survival (OS). Secondary outcome measures include overall response rate (ORR), complete response rate (CRR), duration of response (DoR), event-free survival (EFS), progression-free survival (PFS), time to next treatment (TTNT), treatment discontinuation rate due to adverse events and duration of treatment exposure.

For more information about RE-MIND2, visit View Source

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional marketing authorization in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Monjuvi and Minjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in the EU.

XmAb is a registered trademark of Xencor, Inc.

Important Safety Information

What are the possible side effects of MONJUVI?

MONJUVI may cause serious side effects, including:

Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get fever, chills, rash, flushing, headache, or shortness of breath during an infusion of MONJUVI.
Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or any bruising or bleeding.
Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4°F (38°C) or above, or develop any signs and symptoms of an infection.
The most common side effects of MONJUVI include:

Feeling tired or weak
Diarrhea
Cough
Fever
Swelling of lower legs or hands
Respiratory tract infection
Decreased appetite
These are not all the possible side effects of MONJUVI.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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

Have an active infection or have had one recently.
Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.
You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.
Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.
Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.
You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Please see the full Prescribing Information for Monjuvi, including Patient Information, for additional Important Safety Information.

Karyopharm Announces Presentation of Updated Phase 2 Selinexor Data in Patients with Myelofibrosis at the American Society of Hematology 2021 Annual Meeting and Exposition

On December 11, 2021 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported an oral presentation highlighting updated data from the Phase 2 ESSENTIAL study, an investigator-sponsored study evaluating single-agent selinexor, a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, in patients with myelofibrosis (MF) previously treated with JAK inhibition (Press release, Karyopharm, DEC 11, 2021, View Source [SID1234596811]). These updated results were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 Annual Meeting and Exposition taking place in Atlanta, GA on December 11-14, 2021.

"The results presented at ASH (Free ASH Whitepaper) this year demonstrate that once weekly single-agent oral selinexor resulted in an impressive spleen volume reduction rates in myelofibrosis patients who received at least 24 weeks of treatment, with 40% and 60% of those patients achieving a response, defined as spleen volume reduction (SVR) of at least 35% and 25%, respectively. The durable responses and well-tolerated safety profile highlight selinexor’s potential in patients with JAK-refractory myelofibrosis," said Srinivas Tantravahi, MBBS, MRCP, University of Utah Hospital and principal investigator of the Phase 2 ESSENTIAL study. "With JAK inhibitors being the only class of drugs approved for this disease and with less than half of patients responding, there remains a high unmet need for patients who either progress following treatment with a JAK inhibitor or are intolerant."

"Following the encouraging data from the Phase 2 ESSENTIAL trial, we recently dosed the first patient in Karyopharm’s new Phase 2 study evaluating single-agent selinexor versus physician’s choice in patients with previously treated myelofibrosis," said Sharon Shacham, PhD, MBA, Co-Founder and Chief Scientific Officer of Karyopharm. "As part of our strategic imperatives and pipeline priorities, we remain focused on diseases with the highest unmet needs and greatest potential to make an impact in patient outcomes."

Results from the Phase 2 ESSENTIAL Study Evaluating Single-Agent Selinexor in Patients with MF Refractory or Intolerant to JAK Inhibitors

The results were based on the open label, prospective, investigator-initiated single center ESSENTIAL study in adult patients with primary or secondary MF with resistance or intolerance to JAK inhibitor therapy (NCT03627403). Selinexor was administered orally at a dose of 80mg or 60mg once weekly to 12 patients. The primary endpoint of the study is to assess the efficacy of selinexor on SVR. Median duration of prior JAK inhibitor therapy was 22 months (range 0.5 to 96 months) and 92% (11 of 12) patients had MF refractory to ruxolitinib.

As of the data cutoff, the median duration of treatment was 11 months (range 2.8 to 28.8 months). Of the ten patients who were on treatment for at least 24 weeks, four (40%) patients achieved SVR of ≥35% and six (60%) patients achieved SVR of ≥25%. Of the five patients who were transfusion dependent at screening, two (40%) achieved transfusion independence. Of the three patients with hemoglobin <10g/dL at screening, improvement was observed in two (67%) patients. Reduction in marrow reticulin fibrosis from MF grade 3 to MF grade 1 was observed in a patient who had an assessment at week 72 demonstrating disease modification potential with longer treatment. While median overall survival was not yet reached, the two-year survival probability was assessed to be 91.7%. This compares favorably with a historical survival of 13-14 months in this population.

The most common grade ≥3 treatment emergent adverse events were anemia (33%) and fatigue (33%). These were manageable with treatment interruption and dose reduction, except in one patient who discontinued treatment.

Details for the ASH (Free ASH Whitepaper) 2021 presentation are as follows:

Title: A Phase 2 Study to Evaluate the Efficacy and Safety of Selinexor in Patients with Myelofibrosis Refractory or Intolerant to JAK Inhibitors
Presenter: Srinivas Tantravahi, University of Utah
Abstract #: 143
Session Type: Oral Presentation
Session: Myeloproliferative Syndromes: Clinical and Epidemiological: Non-JAK Inhibitor Therapies for Myelofibrosis

A PDF copy of the presentation is available here.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.