On October 20, 2025 Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (the "Company") reported that the results from the Phase III registrational clinical study OptiTROP-Lung04—led by Professor Zhang Li’s team from Sun Yat-sen University Cancer Center—were published in the New England Journal of Medicine (Impact Factor = 78.5). The study evaluated the efficacy and safety of the TROP2 antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) monotherapy versus pemetrexed plus platinum chemotherapy for the treatment of patients with epidermal growth factor receptor (EGFR)-mutant locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed failed after treatment with EGFR-tyrosine kinase inhibitor (TKI) therapy. The study was also selected as a Late-Breaking Abstract (LBA) at the 2025 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and was presented as an oral report in the Presidential Symposium (Presentation # LBA5).

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OptiTROP-Lung04 is a randomized, open-label, multicenter Phase III study designed to evaluate the efficacy and safety of sac-TMT monotherapy versus pemetrexed plus platinum in patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on prior EGFR-TKI therapy. Eligible patients were those with histologically and/or cytologically confirmed disease. The primary endpoint was Progression-Free Survival (PFS) assessed by a Blinded Independent Review Committee (BIRC) per RECIST v1.1, and the key secondary endpoint was overall survival (OS). Results showed that compared with platinum-based doublet chemotherapy, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in both PFS and OS. Consistent PFS and OS benefits were observed across all prespecified subgroups, including prior EGFR-TKI therapy, presence of liver or brain metastases, and EGFR mutation subtype.

Based on the positive results of the OptiTROP-Lung04 study, sac-TMT has been approved by the National Medical Products Administration (NMPA) in China for the treatment of adult patients with EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC who have progressed after EGFR-TKI therapy. To date, sac-TMT monotherapy remains the only approved treatment option for advanced EGFR-mutant NSCLC patients who have progressed after prior TKI therapy, as well as those who have progressed after prior TKI and platinum-based chemotherapy (either concurrently or sequentially). This achievement provides comprehensive coverage for the entire population of TKI-resistant patients.

Dr. Michael Ge, Chief Executive Officer of Kelun-Biotech, commented: "OptiTROP-Lung04 is a key study that propels sac-TMT from late-line to an earlier-line treatment-setting in lung cancer, achieving a significant improvement in overall survival. We are thrilled that the results have been published in The New England Journal of Medicine, allowing this important finding to be shared widely among medical professionals and providing a reference for future lung cancer research. Together with our partner MSD, we will continue to advance sac-TMT’s clinical development and regulatory approvals, covering broader lung cancer and other indications, with the goal of making sac-TMT a cornerstone therapy for the benefit of patients."

Professor Shengxiang Ren from the Department of Oncology at Shanghai Pulmonary Hospital, Tongji University, stated: "The application of third-generation EGFR-TKIs has significantly improved the overall prognosis for patients with advanced EGFR-mutant NSCLC. However, drug resistance is almost inevitable. Traditional treatment after resistance involves platinum-based doublet chemotherapy, which offers limited overall benefit. In recent years, regimens of chemotherapy plus immune checkpoint inhibitors+anti-angiogenic agents, or EGFR/c-Met bsAb, or PD-1/VEGF bsAb, have been successively approved for this indication. However, all these approaches are chemotherapy-based, highlighting an urgent need to explore novel treatment regimens. The OptiTROP-Lung04 study confirms sac-TMT as the first treatment option as a monotherapy to deliver clear dual benefits in both PFS and OS following EGFR-TKI progression. The sequential application of sac-TMT prior to chemotherapy demonstrates strong competence, establishing itself as a new standard of care for patients with advanced EGFR-mutant lung cancer after TKI resistance."

About Sac-TMT

Sac-TMT, a core product of the Company, is a novel human TROP2 ADC in which the Company has proprietary intellectual property rights, targeting advanced solid tumors such as NSCLC, breast cancer (BC), gastric cancer (GC), gynecological tumors, among others. Sac-TMT is developed with a novel linker to conjugate the payload, a belotecan-derivative topoisomerase I inhibitor with a drug-to-antibody-ratio (DAR) of 7.4. Sac-TMT specifically recognizes TROP2 on the surface of tumor cells by recombinant anti-TROP2 humanized monoclonal antibodies, which is then endocytosed by tumor cells and releases the payload KL610023 intracellularly. KL610023, as a topoisomerase I inhibitor, induces DNA damage to tumor cells, which in turn leads to cell-cycle arrest and apoptosis. In addition, it also releases KL610023 in the tumor microenvironment. Given that KL610023 is membrane permeable, it can enable a bystander effect, or in other words kill adjacent tumor cells.

In May 2022, the Company licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc., Rahway, NJ, USA) to develop, use, manufacture and commercialize sac-TMT in all territories outside of Greater China (includes Mainland China, Hong Kong, Macau, and Taiwan).

To date, three indications for sac-TMT have been approved and marketed in China for the treatment of adult patients with unresectable locally advanced or metastatic triple negative breast cancer (TNBC) who have received at least two prior systemic therapies (at least one of them for advanced or metastatic setting), EGFR mutation-positive locally advanced or metastatic non-squamous NSCLC following progression on EGFR-TKI therapy and platinum-based chemotherapy and EGFR mutant-positive locally advanced or metastatic non-squamous NSCLC who progressed after treatment with EGFR-TKI therapy. Sac-TMT is the first TROP2 ADC drug approved for marketing in lung cancer globally. In addition, the new indication application for sac-TMT for the treatment of adult patients with unresectable locally advanced, metastatic hormone receptor positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC who have received prior endocrine therapy and other systemic treatments in the advanced or metastatic setting was accepted by the Center for Drug Evaluation of the NMPA, and was included in the priority review and approval process.

As of today, the Company has initiated 9 registrational clinical studies in China. MSD has initiated 15 ongoing Phase Ⅲ global clinical studies of sac-TMT as a monotherapy or with pembrolizumab1 or other anti-cancer agents for several types of cancer. These studies are sponsored and led by MSD.

(Press release, Kelun, OCT 20, 2025, View Source [SID1234656832])

On October 20, 2025 GRAIL, Inc. (Nasdaq: GRAL), a healthcare company whose mission is to detect cancer early when it can be cured, and the University of Oxford, reported that positive long-term results from an extended registry follow-up of the SYMPLIFY study will be presented on Oct. 21 at the Early Detection of Cancer Conference (EDCC) in Portland, Oregon.

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SYMPLIFY, a prospective observational study, is the first large-scale evaluation of a multi-cancer early detection (MCED) test in individuals who presented with symptoms to primary care and were referred for diagnostic follow-up for suspicion of cancer. In SYMPLIFY, the Galleri test was used to assess blood samples from more than 6,000 participants with symptoms of cancer who followed standard diagnostic pathways. However, as a non-interventional study, the results of the tests were unknown to physicians and did not inform the approach to diagnosis. No MCED results were returned to participants or their clinicians during the study.

"The conversion of false positive results to cancer diagnosis in this updated analysis of the SYMPLIFY study highlights the importance of proactive follow-up on positive MCED results, as one third of the apparent false positive results were actually cancers the standard-of-care diagnostic process couldn’t immediately identify," said Brian D. Nicholson, MRCGP, DPhil, Associate Professor at the Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom and co-lead investigator of the study. "Additionally, the results underscore the value of Galleri’s Cancer Signal Origin prediction, which aligned with the eventual diagnosis in almost all of the cases initially considered to be false positives. We are pleased to present these data at EDCC and have submitted this analysis for full publication."

Previous SYMPLIFY results showed potential of MCED testing in people with symptoms suggestive of cancer

Most people diagnosed with cancer visit primary care with symptoms before diagnosis1. Many of these people report common, non-specific symptoms such as bloating, unexplained weight loss or abdominal pain, which can be attributed to various conditions as well as cancer2.

The primary analysis of the SYMPLIFY study, previously published in The Lancet Oncology, supported the feasibility of using the Galleri test to assist clinicians with decisions regarding referral from primary care. In that analysis, which followed participants until diagnostic resolution or up to nine months, Galleri’s positive predictive value (PPV) was 75.5%. When a cancer signal was detected, the test accurately predicted the Cancer Signal Origin (CSO) in 84.8% of cases.

Updated results demonstrate importance of continued follow-up after a cancer signal is detected

Patients reported to have a false positive Galleri result were followed for 24 months in national cancer registries for England and Wales. The analysis showed that 35.4% (28 of 79 participants) were later diagnosed with cancer within 24 months of enrollment. This reduction in false positives from 79 to 51 resulted in an increase of PPV to 84.2%. In aggregate, 27 of these 28 participants had a correct CSO prediction which could have led to a faster or more efficient diagnosis. In more than half of these cases, the cancer type diagnosed was not congruent with the original diagnostic clinic to which the patient was referred by the general practitioner based on the clinical presentation:

16 of the 28 (57.1%) were diagnosed with cancer within nine months of enrollment.
Eight of the 16 (50%) were diagnosed with cancers that were correctly predicted by the Galleri test’s CSO finding, but were incongruent with the diagnostic pathway chosen by the general practitioner based on the participants’ presenting symptoms.
12 of the 28 (42.9%) were diagnosed 10-24 months after enrollment.
Seven of the 12 (58.3%) were diagnosed outside the original referral pathway; in those cases, the CSO also was correct, matching the site that was ultimately diagnosed.
"The SYMPLIFY study, focused on patients presenting with symptoms, adds to the breadth of our clinical experience in asymptomatic populations. This robust data demonstrates the potential benefit of the Galleri test as a diagnostic tool for individuals presenting with symptoms of cancer, particularly where those symptoms are non-specific. The fact that, in all but one of the additional patients diagnosed with cancer, a Galleri CSO prediction correctly identified the cancer type, including in many cases where the symptoms were non-specific, further reinforces the value of the Galleri test’s CSO capability," said Sir Harpal Kumar, President, International Business & BioPharma at GRAIL. "Furthermore, the 24-month follow-up data being presented at EDCC underscore the importance of continued follow-up to help identify cancers that may initially be missed in diagnostic evaluation. These latest results add to the body of evidence that Galleri could support clinical decision-making in primary care for referral to urgent diagnostic investigations of cancer and drive more efficient use of diagnostic capacity."

About the SYMPLIFY Study
SYMPLIFY is a prospective multicentre observational study and represents the first large-scale evaluation of an MCED test in symptomatic patients who were referred from the primary care setting due to clinical suspicion of cancer. The study enrolled 6,238 patients, aged 18 years and older, in England and Wales who were referred for urgent imaging, endoscopy or other diagnostic modalities to investigate symptoms suspicious for possible cancer. Of the total enrolled patients, there were 5,461 evaluable patients who achieved diagnostic resolution. GRAIL’s MCED test was performed in batches, blinded to clinical outcome, and results were compared with the diagnosis obtained by standard of care pathways to assess the test’s performance.

The University of Oxford sponsored the SYMPLIFY study and was responsible for data collection, analysis and interpretation. The study was funded by GRAIL with support from National Health Service (NHS) England, NHS Wales, the National Institute for Health and Care Research (NIHR) and NIHR Oxford Biomedical Research Centre.

(Press release, Grail, OCT 20, 2025, View Source [SID1234656831])

On October 20, 2025 GRAIL, Inc. (Nasdaq: GRAL), a healthcare company whose mission is to detect cancer early when it can be cured, reported that it has entered into a securities purchase agreement for a private placement that is expected to result in gross proceeds of approximately $325.0 million, before deducting placement agents’ fees and other expenses.

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The private placement included the participation by new and existing institutional investors, including Deep Track Capital, Farallon Capital Management, Hims & Hers, Braidwell LP, three life sciences investment firms, and a tech and life sciences focused family office investment firm.

GRAIL currently expects to use the net proceeds from the private placement to fund its commercial activities and reimbursement efforts, as well as for working capital and other general corporate purposes.

GRAIL believes its cash, cash equivalents and investments, including the expected net proceeds from the private placement, will provide sufficient funding of planned operations into 2030, not including the previously announced agreement by Samsung C&T and Samsung Electronics to invest $110 million in the Company, subject to closing conditions.

Pursuant to the terms of the securities purchase agreement, GRAIL has agreed to issue and sell 4,639,543 shares of common stock (or pre-funded warrants in lieu thereof) at a price per share of $70.05 (or per pre-funded warrant in lieu thereof, less the nominal exercise price of $0.001 per share).The private placement is expected to close on October 21, 2025, subject to the satisfaction of customary closing conditions.

Morgan Stanley acted as lead placement agent and Goldman Sachs & Co. LLC acted as joint placement agent for the private placement.

The securities sold in this private placement, including the shares of common stock underlying the pre-funded warrants, have not been registered under the Securities Act of 1933, as amended, or applicable state securities laws, and may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements. GRAIL granted registration rights to the purchasers in the private placement and has agreed to file a registration statement with the Securities and Exchange Commission registering the resale of the shares of common stock and the shares of common stock underlying the pre-funded warrants issued in the private placement.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

(Press release, Grail, OCT 20, 2025, View Source [SID1234656830])

On October 20, 2025 MEDSIR, the leading international oncology research company, reported the positive results of its EMPRESS study, conducted in collaboration with Roche Farma. This is an international, multicenter Phase II trial that evaluates the potential benefit of the drug giredestrant, a potent oral selective estrogen receptor degrader (SERD), in premenopausal women with early-stage ER+/HER2- breast cancer.

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The results, presented at the congress during an oral session, demonstrated that giredestrant, administered as a single agent in the preoperative setting, shows greater activity compared to standard treatment with tamoxifen in slowing the proliferation of tumor cells. The study met its primary endpoint by showing that, after 15 days of treatment, patients receiving giredestrant experienced a significant reduction in the tumor proliferation marker Ki-67. This protein appears in cells when they are dividing, so its reduction indicates a positive response to treatment.

One of the most relevant findings of the study is that, for the first time, this reduction in tumor activity is achieved without suppressing the patient’s ovarian function. This suggests that giredestrant could represent a more effective oral therapeutic alternative to the current standard therapy, with the potential to improve patients’ quality of life by avoiding the adverse effects associated with ovarian suppression, which is typically performed with injections of luteinizing hormone-releasing hormone (LHRH) analogs.

"The results of the EMPRESS study are very promising, as they indicate greater activity of giredestrant compared to tamoxifen in slowing tumor proliferation, as measured by Ki-67," said Dr. Antonio Llombart-Cussac, principal investigator of the study, during the presentation. He also emphasized that "this study opens the door to exploring the potential use of giredestrant without ovarian function suppression in premenopausal women, which could significantly improve patients’ quality of life by avoiding the side effects associated with traditional treatment."

Theranostics: The Revolution in Oncology

As part of the congress and its commitment to international collaboration and innovation, MEDSIR held a new edition of its MEDTalks forum in Berlin, supported by Telix Pharma. During the event, the company brought together leading national and international oncology experts, including Dr. Matthias Preusser (Medical University of Vienna), Dr. Nathalie Albert (Ludwig Maximilian University of Munich), Dr. Christophe Deroose (KU Leuven), and Dr. Jaume Capdevila (Vall d’Hebron Institute of Oncology, VHIO). The goal of this edition was to explore the crucial role of theranostics in optimizing cancer research.

Under the title "Understanding the Challenge in Clinical Trials," the discussion addressed the importance of implementing this new approach in oncology, which combines imaging-based diagnosis with precision therapy. This therapeutic strategy benefits patients in more advanced stages with limited treatment options through the administration of a radiopharmaceutical—first to visualize the tumor (diagnosis) and then to treat it (therapy).

MEDSIR Reinforces Its Commitment to Breast Cancer at ESMO (Free ESMO Whitepaper) 2025

In addition to the oral presentation of EMPRESS results, MEDSIR’s active participation in the ESMO (Free ESMO Whitepaper) congress includes the poster presentation of the TELESCOPE study. This ongoing national phase II clinical trial, conducted in collaboration with pharmaceutical company Merck Sharp & Dohme, evaluates the addition of pembrolizumab to carboplatin and paclitaxel treatment during 12 weeks prior to surgery for patients with stage I triple-negative breast cancer. The goal is to assess the pathological complete response (pCR) rate to preoperative treatment.

(Press release, MedSIR, OCT 20, 2025, View Source;breast-cancer-at-early-stages-without-the-need-for-ovarian-function-suppression-302588871.html [SID1234656829])

On October 20, 2025 Citius Oncology, Inc. ("Citius Oncology") (Nasdaq: CTOR), the oncology-focused subsidiary of Citius Pharmaceuticals, Inc. ("Citius Pharma") (Nasdaq: CTXR), reported it has entered into a distribution services agreement with McKesson Corporation (NYSE: MCK), one of the largest pharmaceutical distributors and healthcare services companies in North America. Under the agreement, McKesson will serve as an authorized distributor of record for LYMPHIR (denileukin diftitox-cxdl), a novel immunotherapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

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The agreement with McKesson completes Citius Oncology’s core U.S. distribution network for LYMPHIR, which now includes all three of the largest pharmaceutical distributors in the country. This strategic milestone ensures broad and reliable access to the therapy in preparation for its planned commercial launch in the fourth quarter of 2025.

"This agreement marks the final major component of our U.S. distribution strategy and reflects our deep commitment to ensuring that physicians and patients have timely access to LYMPHIR," said Leonard Mazur, Chairman and CEO of Citius Oncology and Citius Pharmaceuticals. "With a complete top-tier distribution network in place, we believe we are well-positioned to deliver on our promise to the CTCL community and execute a successful launch."

Headquartered in Irving, Texas, McKesson Corporation is a global leader in healthcare supply chain management, medical products distribution, and pharmaceutical logistics. The company supports thousands of hospitals, clinics, and pharmacies across the United States, making it a critical partner for enabling access to life-saving therapies like LYMPHIR.

Citius Oncology has now finalized distribution agreements with all three of the largest U.S. pharmaceutical wholesalers and specialty distributors, paving the way for broad national access across both academic centers and community oncology practices. These efforts complement the Company’s ongoing commercialization activities, including inventory readiness, market access infrastructure, permanent J-code assignment (J9161), NCCN guideline inclusion, and a robust suite of provider and patient education resources.

About LYMPHIR (denileukin diftitox-cxdl)

LYMPHIR is a targeted immune therapy for relapsed or refractory cutaneous T-cell lymphoma (CTCL) indicated for use in Stage I-III disease after at least one prior systemic therapy. It is a recombinant fusion protein that combines the IL-2 receptor binding domain with diphtheria toxin fragments. The agent specifically binds to IL-2 receptors on the cell surface, causing diphtheria toxin fragments that have entered cells to inhibit protein synthesis. After uptake into the cell, the DT fragment is cleaved and the free DT fragments inhibit protein synthesis, resulting in cell death. Denileukin diftitox-cxdl demonstrated the ability to deplete immunosuppressive regulatory T lymphocytes (Tregs) and antitumor activity through a direct cytocidal action on IL-2R-expressing tumors.

In 2021, denileukin diftitox received regulatory approval in Japan for the treatment of CTCL and PTCL. Subsequently, in 2021, Citius acquired an exclusive license with rights to develop and commercialize LYMPHIR in all markets except for Japan and certain parts of Asia. LYMPHIR was approved by the FDA in August 2024.

About Cutaneous T-cell Lymphoma

Cutaneous T-cell lymphoma is a type of cutaneous non-Hodgkin lymphoma (NHL) that comes in a variety of forms and is the most common type of cutaneous lymphoma. In CTCL, T-cells, a type of lymphocyte that plays a role in the immune system, become cancerous and develop into skin lesions, leading to a decrease in the quality of life of patients with this disease due to severe pain and pruritus. Mycosis Fungoides (MF) and Sézary Syndrome (SS) comprise the majority of CTCL cases. Depending on the type of CTCL, the disease may progress slowly and can take anywhere from several years to upwards of ten to potentially reach tumor stage. However, once the disease reaches this stage, the cancer is highly malignant and can spread to the lymph nodes and internal organs, resulting in a poor prognosis. Given the duration of the disease, patients typically cycle through multiple agents to control disease progression. CTCL affects men twice as often as women and is typically first diagnosed in patients between the ages of 50 and 60 years of age. Other than allogeneic stem cell transplantation, for which only a small fraction of patients qualify, there is currently no curative therapy for advanced CTCL.

INDICATION

LYMPHIR is an IL2-receptor-directed cytotoxin indicated for the treatment of adult patients with r/r Stage I-III cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: CAPILLARY LEAK SYNDROME

Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity.

WARNINGS AND PRECAUTIONS

Capillary Leak Syndrome

LYMPHIR can cause capillary leak syndrome (CLS), including life-threatening or fatal reactions. CLS was defined in the clinical trials as the occurrence of at least 2 of the following symptoms at any time during LYMPHIR therapy: hypotension, edema, and serum albumin <3 g/dL. These symptoms were not required to occur simultaneously to be characterized as capillary leak syndrome.

As defined, CLS occurred in 27% of patients in the pooled population across 3 clinical trials, including 8% with Grade 3. There was one (0.8%) fatal occurrence of CLS. Of the patients with CLS, 22% had recurrence. The majority of CLS events (81%) occurred within the first 2 cycles of treatment. The median time to onset from Cycle 1, Day 1 was 6.5 days (range: 1 to 77), the median duration of CLS was 14 days (range: 2 to 40), and 75% of patients had resolution. The most common symptoms included edema, hypoalbuminemia, and hypotension. Pleural effusion, pericardial effusion, and dehydration also occurred.

Regularly assess patients for weight gain, new onset or worsening of edema, dyspnea, and hypotension (including orthostatic changes). Monitor serum albumin levels prior to the initiation of each cycle of therapy and more often as clinically indicated.

Withhold, reduce dose, or permanently discontinue based on severity. If LYMPHIR is withheld, resume LYMPHIR following resolution of CLS and when serum albumin is greater than or equal to 3 g/dL.

Visual Impairment

LYMPHIR can cause serious visual impairment, including changes in visual acuity and color vision. In the pooled population across 3 clinical trials, visual impairment occurred in 9%, with Grade 1 in 8% and Grade 2 in 1%. The most commonly reported symptom was blurred vision. Of the patients with visual impairment, 67% had resolution of their visual impairment.

Perform baseline ophthalmic examination and monitor as clinically indicated. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, or blurred vision, refer for ophthalmologic evaluation.

Withhold LYMPHIR until visual impairment resolves or permanently discontinue based on severity.

Infusion-Related Reactions

LYMPHIR can cause serious infusion-related reactions. Infusion-related reactions were reported in 69% of patients in the pooled population across 3 clinical trials of patients who received LYMPHIR, with Grade 3 infusion-related reactions in 3.4% [see Adverse Reactions (6.1)]. Eighty-three percent of infusion-related reactions occurred in Cycles 1 and 2. The most common symptoms included nausea, fatigue, chills, musculoskeletal pain, vomiting, fever, and arthralgia.

Premedicate patients for the first three cycles prior to starting a LYMPHIR infusion [see Dosage and Administration (2.3)]. Monitor patients frequently during infusion. For Grade 2 or higher infusion reactions, premedicate at least 30 minutes prior to each subsequent infusion with a systemic steroid for at least 3 cycles.

Interrupt or discontinue LYMPHIR based on severity [see Dosage and Administration (2.4)]. Institute appropriate medical management.

Hepatotoxicity

LYMPHIR can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 70% of patients, with Grade 3 ALT occurring in 22%; elevated AST occurred in 64% of patients, with Grade 3 AST elevation occurring in 9%. For Grade 3 events, median time to onset was 8 days (range: 1 to 15 days); median time to resolution was 15 days (range: 7 to 50 days); all cases of Grade 3 ALT or AST elevations resolved [see Adverse Reactions (6.1)]. Elevated total bilirubin occurred in 5% of patients, with Grade 3 occurring in 0.9%.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold, reduce dose, or permanently discontinue LYMPHIR based on severity.

Embryo-Fetal Toxicity

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of LYMPHIR. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment and for 7 days following the last dose of LYMPHIR.

ADVERSE REACTIONS

The most common adverse reactions (≥20%), including laboratory abnormalities, are increased transaminases, albumin decreased, nausea, edema, hemoglobin decreased, fatigue, musculoskeletal pain, rash, chills, constipation, pyrexia, and capillary leak syndrome

USE IN SPECIFIC POPULATIONS

Pregnancy

Risk Summary
Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman. There are no available data on the use of LYMPHIR in pregnant women to evaluate for a drug-associated risk. No animal reproductive and developmental toxicity studies have been conducted with denileukin diftitox.

Denileukin diftitox-cxdl causes depletion of regulatory T lymphocytes (Treg), immune activation, and capillary leak syndrome, compromising pregnancy maintenance. Advise pregnant women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively.

Lactation

Risk Summary
No data are available regarding the presence of denileukin diftitox-cxdl in human milk, the effects on the breastfed child, or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with LYMPHIR and for 7 days after the last dose.

Females and Males of Reproductive Potential

Based on its mechanism of action, LYMPHIR can cause fetal harm when administered to a pregnant woman.

Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating LYMPHIR.

Contraception

Females
Advise females of reproductive potential to use effective contraception during treatment with LYMPHIR and for 7 days after the last dose.

Infertility

Males
Based on findings in rats, male fertility may be compromised by treatment with LYMPHIR. The reversibility of the effect on fertility is unknown.

Pediatric Use
Safety and effectiveness of LYMPHIR in pediatric patients have not been established.

Geriatric Use
Of the 69 patients with Stage I-III r/r CTCL who received LYMPHIR, 34 patients (49%) were 65 years of age and older and 10 patients (14%) were 75 years of age and older. Clinical studies of LYMPHIR did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . You may also report side effects to Citius Oncology, Inc. at 1-844-459-6744.

Please read Important Safety Information and full Prescribing Information, including Boxed WARNING, for LYMPHIR.

(Press release, Citius Oncology, OCT 20, 2025, View Source [SID1234656828])