On September 10, 2025 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that it has completed enrollment in the Phase 3 SENTRY trial, which is evaluating selinexor in combination with ruxolitinib in JAKi-naïve myelofibrosis patients (Press release, Karyopharm, SEP 10, 2025, View Source [SID1234655924]).

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"We are excited to announce that we have completed enrollment of our Phase 3 SENTRY trial and look forward to sharing top-line data from this pivotal trial in March 2026," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "Selinexor plus ruxolitinib has the potential to be the first combination therapy approved for the treatment of myelofibrosis, depending on the outcome of the data. By combining selinexor with the current standard of care, we believe we have the potential to redefine the way people living with myelofibrosis are treated."

"I am grateful for the patients, their families and caregivers, the investigators and their clinical trial staff, as well as the extraordinary efforts of the Karyopharm team and our external partners for their help in successfully achieving this important milestone," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research of Karyopharm. "This trial is advancing our understanding of the treatment of myelofibrosis and the potential role that XPO1 inhibition may play in this disease. People living with myelofibrosis deserve new treatment options and everyone involved in SENTRY is making an important contribution towards our common goal of providing additional options to patients with this disease."

"We are encouraged by the work that Karyopharm is doing in myelofibrosis and eagerly await data from the Phase 3 SENTRY trial," said Kapila Viges, Chief Executive Officer of MPN Research Foundation. "The myelofibrosis community is in need of new, more effective therapies that can help a greater number of patients beyond what is available with currently approved options. Efforts to develop new therapies bring hope to the myelofibrosis community and open the potential for patients to have more treatment options. For patients, options matter."

SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 109/L. Patients are randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume response rate ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline. The Phase 3 trial enrolled 353 patients.

About Myelofibrosis

Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 17,000 patients in the European Union1. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib. Patients treated with the most commonly prescribed JAK inhibitor often require blood transfusions, and more than 30% will discontinue treatment due to anemia.2 Anemia and transfusion dependence are strongly correlated with poor prognosis and shortened survival.3

1. Clarivate/DRG (2023)
2. Palandri, F., Palumbo, G.A., Elli, E.M. et al. Ruxolitinib discontinuation syndrome: incidence, risk factors, and management in 251 patients with myelofibrosis. Blood Cancer J. 11, 4 (2021).
3. Pardanani, A., & Tefferi, A. (2011). Prognostic relevance of anemia and transfusion dependency in myelodysplastic syndromes and primary myelofibrosis. Haematologica, 96(1), 8–10.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with VELCADE (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma; and (iii) under accelerated approval in adult patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO/NEXPOVIO is marketed in these respective ex-U.S. territories by Karyopharm’s partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.

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 two 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.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or www.fda.gov/medwatch.

On September 10, 2025, Intensity Therapeutics, Inc. (the "Company") reported an update on it’s INVINCIBLE-4 study (Press release, Intensity Therapeutics, SEP 10, 2025, View Source [SID1234655923]). The update reported that a pathological complete response ("pCR") was observed in the first patient evaluated in Cohort A, where each patient received two doses of INT230-6 eight days apart, followed by the standard of care immunochemotherapy, and that to date, the safety profile looks favorable in Cohort A. However, some patients in Cohort A experienced localized skin irritation near the tumor site and therefore, new patient enrollment has been paused to evaluate the data collected and to implement necessary adjustments prior to reopening patient enrollment.

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On September 10, 2025 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing a pipeline of novel therapies, reported that ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX Code: 1541.HK) ("ImmuneOnco") presented preliminary efficacy and safety data of ‘2510 (IMM2510/AXN-2510) as monotherapy in a Phase 1 study of patients in China with previously treated squamous non-small cell lung cancer (sq-NSCLC) at the 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain on September 9, 2025 (Press release, Instil Bio, SEP 10, 2025, View Source [SID1234655922]).

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ImmuneOnco reported that 23 patients with sq-NSCLC had been treated with monotherapy ‘2510 as of June 13, 2025. All patients had failed previous PD-(L)1 inhibitor plus platinum-doublet chemotherapy, and 6 patients had previously received VEGF-directed therapy. Patients were treated with ‘2510 at different dose levels (3, 6, 10, or 20 mg/kg Q2W), with the majority of patients treated at the 20 mg/kg Q2W dose level. In the 17 efficacy evaluable patients, the objective response rate ("ORR") was 35.3%, with the majority of responses seen in patients with negative and low PD-L1 TPS scores. Most patients remain on treatment with the opportunity for additional tumor assessments, including multiple patients currently with stable disease. In general, ‘2510 was safe and well tolerated across the Phase 1 trial, with mostly manageable low grade infusion reactions in the first cycle as previously reported. In the squamous subset there were two Grade 3 VEGF-related adverse events of proteinuria and bleeding. Enrollment is continuing at the 20 mg/kg Q2W dose level in this study.

"’2510 was designed for potential best-in-class activity with a VEGF trap for broader neutralization of VEGF ligands and ADCC enhancement for direct tumor killing," said Jamie Freedman, M.D., Ph.D., Chief Medical Officer of Instil. "ImmuneOnco’s promising preliminary monotherapy data for ‘2510 in patients with sq-NSCLC who have failed prior therapies compares favorably with other molecules in the PD-(L)1xVEGF bispecific class."

On September 10, 2025 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company focused on keeping cancer patients alive, reported to share updated overall survival data in first-line pancreatic cancer patients treated with atebimetinib + mGnP (N=34) with 9 months median follow up on Thursday, September 25, 2025 (Press release, Immuneering, SEP 10, 2025, View Source [SID1234655921]). The Company additionally shared plans for two presentations at upcoming scientific conferences.

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Presentations:

Updated Overall Survival Data in First-Line Pancreatic Cancer Patients Treated with Atebimetinib + mGnP (N=34), with 9 Month Median Follow Up. Immuneering plans to host an investor call at 8 a.m. ET on September 25, 2025. The conference call will be webcast live and archived in the Investor Relations section of Immuneering’s website at Events & Presentations | Immuneering Corporation.
Encore Presentation of Updated Overall Survival Data in First-Line Pancreatic Cancer Patients Treated with Atebimetinib + mGnP at the PanCAN Scientific Summit. Immuneering plans to present a poster titled "Atebimetinib + mGnP: Overall Survival and Safety in First Line Pancreatic Cancer Patients" on Sunday September 28 at the Pancreatic Cancer Action Network (PanCAN) Scientific Summit 2025 in Boston MA. The presentation will be made from 7:30 – 8:20am and from 12:20 – 1:10pm ET.
Review of Preclinical Data on Deep Cyclic Inhibitors. The Company additionally plans to make an oral presentation titled "Deep Cyclic Inhibition of MEK: A Transformational Approach to Durable and Safe Combinations in RAS-Mutant Cancers" on September 17 at the 7th RAS-Targeted Drug Development Summit taking place September 16-18, in Boston, MA at 4:15pm ET.
"We are excited to share updated overall survival data from our ongoing Phase 2a trial of atebimetinib in combination with mGnP in first-line pancreatic cancer patients. Nine months median follow up is an important milestone because, sadly, less than half of the patients treated with standard of care gemcitabine/nab-paclitaxel in this setting survive 9 months," said Ben Zeskind, Ph.D., Co-founder and Chief Executive Officer of Immuneering. "We previously reported an exceptional 94% OS observed at 6 months in first-line pancreatic cancer patients treated with atebimetinib in combination with mGnP. To put that in perspective, in the pivotal study of standard of care GnP, the 6-month OS was only 67%, and dropped rapidly to approximately 47% by 9 months."

Zeskind continued: "Atebimetinib was designed for durability and tolerability, and we believe it has the potential to deliver what has long been missing in pancreatic cancer care: a drug that helps patients live longer and thrive without serious side effects. PanCAN is a world-class organization dedicated to making life better for pancreatic cancer patients, and so we are excited to share these updates with the oncology community at the PanCAN Scientific Summit 2025."

On September 10, 2025 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on its Phase III clinical trial, FLAMINGO-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences, reported that FDA has granted Fast Track designation for GLSI-100 in the HLA-A*02 patient population (Press release, Greenwich LifeSciences, SEP 10, 2025, View Source [SID1234655920]).

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The designation specifically states that "GLSI-100 for the treatment of patients with HLA-A*02 genotype and HER2-positive breast cancer who have completed treatment with standard of care HER2/neu targeted therapy to improve invasive breast cancer free survival meets the criteria for Fast Track designation."

The Fast Track designation for GLSI-100 may lead to earlier drug approval as the Company and the FDA can communicate more frequently to expedite the Biologic License Application (BLA) filing of the clinical and manufacturing data from FLAMINGO-01. The Company may be able to utilize a rolling review process, where completed parts of the BLA can be submitted for review, even though other parts of the application are still being completed.

Dr. Jaye Thompson, VP Clinical and Regulatory Affairs, commented, "Greenwich is pleased that the FDA sees the potential of GLSI-100 to change important clinical outcomes in this population of breast cancer patients. We continue to work earnestly to collect data to support a BLA filing demonstrating this benefit."

CEO Snehal Patel commented, "We are excited to have received Fast Track designation. The FDA review of our Fast Track application included a review of the potential of GLSI-100 as a new drug to treat serious conditions and to fill unmet medical need. By showing the potential of GLSI-100 to prevent metastatic breast cancer recurrence in the patient population that we are studying, we were able to estimate the potential lives that could be saved. The Company plans to continue discussions with the FDA, and potentially the European regulatory authorities, to explore additional ways to make GP2 and GLSI-100 available to larger populations."

A description of the Fast Track criteria and process is available on the FDA website:
View Source

As described by the FDA website:

"Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions…Filling an unmet medical need is defined as providing a therapy where none exists or providing a therapy which may be potentially better than available therapy…Once a drug receives Fast Track designation, early and frequent communication between the FDA and a drug company is encouraged throughout the entire drug development and review process. The frequency of communication assures that questions and issues are resolved quickly, often leading to earlier drug approval and access by patients."

The FDA website further states:

"Any drug being developed to treat or prevent a condition with no current therapy obviously is directed at an unmet need. If there are available therapies, a fast track drug must show some advantage over available therapy, such as:

Showing superior effectiveness, effect on serious outcomes or improved effect on serious outcomes
Avoiding serious side effects of an available therapy
Improving the diagnosis of a serious condition where early diagnosis results in an improved outcome
Decreasing a clinical significant toxicity of an available therapy that is common and causes discontinuation of treatment
Ability to address emerging or anticipated public health need
A drug that receives Fast Track designation is eligible for some or all of the following:

More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA"
Previously Published Phase IIb Data

In the prospective, randomized, single-blinded, placebo-controlled, multi-center (16 sites led by MD Anderson Cancer Center) Phase IIb clinical trial of HLA-A*02 breast cancer patients, 46 HER2/neu 3+ over-expressor patients were treated with GLSI-100, and 50 placebo patients were treated with GM-CSF alone. After 5 years of follow-up, there was an 80% or greater reduction in cancer recurrences in the HER2/neu 3+ patients who were treated with GLSI-100, followed, and remained disease free over the first 6 months, which we believe is the time required to reach peak immunity and thus maximum efficacy and protection. The Phase IIb results can be summarized as follows:

80% or greater reduction in metastatic breast cancer recurrence rate over 5 years of follow-up compared to 20-50% reduction in recurrence rate by other approved products
Peak immune response at 6 months
No reported serious adverse events attributable to treatment
Well-tolerated safety profile
Full immunization was received in the Primary Immunization Series (PIS), which included the first 6 GLSI-100 injections over the first 6 months. The PIS elicited a potent immune response as measured by local skin tests and immunological assays. Further, booster injections given every 6 months prolonged the immune response, thereby providing longer-term protection. In the Phase IIb and three Phase I clinical trials, where 146 patients were treated, the GP2 immunotherapy was well tolerated, and there were no reported serious adverse events related to GLSI-100.

About FLAMINGO-01 and GLSI-100

FLAMINGO-01 (NCT05232916) is a Phase III clinical trial designed to evaluate the safety and efficacy of GLSI-100 (GP2 + GM-CSF) in HER2 positive breast cancer patients who had residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab based treatment. The trial is led by Baylor College of Medicine and currently includes US and European clinical sites from university-based hospitals and academic and cooperative networks with plans to open up to 150 sites globally. In the double-blinded arms of the Phase III trial, approximately 500 HLA-A*02 patients will be randomized to GLSI-100 or placebo, and up to 250 patients of other HLA types will be treated with GLSI-100 in a third arm. The trial has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater.

For more information on FLAMINGO-01, please visit the Company’s website here and clinicaltrials.gov here. Contact information and an interactive map of the majority of participating clinical sites can be viewed under the "Contacts and Locations" section. Please note that the interactive map is not viewable on mobile screens. Related questions and participation interest can be emailed to: [email protected]

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 300,000 new breast cancer patients and 4 million breast cancer survivors. HER2 (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.