OS Therapies Initiates Commercial-ready Manufacturing of OST-HER2 to Support Anticipated Biologics Licensing Authorization (BLA) Filing

On February 14, 2025 OS Therapies, Inc. (NYSE-A: OSTX), a clinical-stage biotechnology company advancing immunotherapies and targeted drug conjugates for cancer treatment, reported that it has entered into agreements for the commercial manufacture of OST-HER2 (Press release, OS Therapies, FEB 14, 2025, View Source [SID1234650299]). The Company is currently organizing additional data in relation to the recently-completed treatment phase of its Phase 2b trial of OST-HER2 in the prevention of recurrence of lung metastatic osteosarcoma in preparation for a Type B or Type C meeting with the US Food & Drug Administration ("FDA"). Following the FDA meeting, the Company anticipates that it will be submitting a Biologics Licensing Authorization (BLA) application to the FDA for accelerated or conditional approval consideration.

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U.S. FDA Grants Full Approval of Deciphera’s ROMVIMZA™ (vimseltinib) for the Treatment of Symptomatic Tenosynovial Giant Cell Tumor (TGCT)

On February 14, 2025 Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President: Toichi Takino; "Ono") reported that the U.S. Food and Drug Administration (FDA) has approved ROMVIMZA (vimseltinib), a kinase inhibitor, for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity (Press release, , FEB 14, 2025, View Source [SID1234650298]). The FDA previously granted Fast Track designation and Priority Review for ROMVIMZA, which was developed by Deciphera Pharmaceuticals, Inc. ("Deciphera"), a wholly owned subsidiary of Ono.

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"The approval of ROMVIMZA provides a new, much-needed, well-tolerated, and effective treatment option for people suffering from TGCT," said Hans Gelderblom, M.D., Ph.D., Chair of the Department of Medical Oncology at Leiden University Medical Center. "TGCT adversely affects the lives of patients, causing significant pain, limited mobility, and stiffness. The MOTION Phase 3 study demonstrated ROMVIMZA’s ability to shrink tumors along with being the first well-tolerated agent to demonstrate significant improvement in a number of other important quality-of-life measures without any observed liver injury as seen with other approved TGCT treatment. ROMVIMZA is a differentiated treatment that has the potential to address the significant unmet needs of the TGCT community."

"The FDA approval of ROMVIMZA for TGCT is a crucial advancement for the TGCT community and we believe ROMVIMZA has the potential to become the new standard of care for people with TGCT for which surgical resection will potentially cause worsening functional limitation or severe morbidity. This is also an important milestone for our organization, as it is the second approved therapy discovered using Deciphera’s proprietary switch-control kinase inhibitor platform," said Ryota Udagawa, President and Chief Executive Officer of Deciphera Pharmaceuticals. "I’d like to extend my gratitude to the patients, families, caregivers, and healthcare providers who contributed to the success in ROMVIMZA’s clinical studies. Their commitment, along with the dedication of the Deciphera and Ono teams, enabled us to advance this impactful new treatment, which we look forward to delivering to patients."

TGCT is a rare, non-malignant tumor that forms within or near joints. TGCT arises from the dysregulation of the CSF1 gene, resulting in an overproduction of CSF1. If left untreated or if the tumor repeatedly recurs, it can lead to damage and degeneration in the affected joint and surrounding tissues, potentially causing significant disability.

The FDA approval was based on the efficacy and safety results from the pivotal Phase 3 MOTION study of ROMVIMZA in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed), compared to placebo, as well as the Phase 1/2 study of ROMVIMZA. In MOTION, ROMVIMZA demonstrated a statistically significant and clinically meaningful ORR at Week 25 in the intent-to-treat (ITT) population, as assessed by blinded independent radiologic review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo (40% in ROMVIMZA arm vs 0% in placebo arm, p <0.0001). The primary endpoint was supported by statistically significant and clinically meaningful improvements in active range of motion, patient-reported physical functioning, and patient-reported pain observed in the vimseltinib arm compared to the placebo arm at week 25. The safety profile of ROMVIMZA is manageable and consistent with results previously disclosed in the Phase 1/2 clinical trial.

Deciphera Pharmaceuticals plans to make ROMVIMZA commercially available in the U.S. next week. Learn more at www.ROMVIMZA.com.

In July of 2024, the Company announced the marketing authorization application (MAA) for ROMVIMZA for the treatment of patients with TGCT was accepted and is under review by the European Medicines Agency (EMA).

Deciphera is committed to supporting TGCT patients and providers in navigating coverage and access to ROMVIMZA. As part of that commitment, Deciphera AccessPointTM, a patient support program, is available to provide comprehensive access and financial assistance programs for eligible patients. For more information, visit DecipheraAccessPoint.com or call 1-833-4DACCES (1-833-432-2237), Monday-Friday, 8:00 AM to 8:00 PM Eastern Time (ET).

About MOTION Study

The MOTION study is a two-part, randomized, double-blind, placebo-controlled Phase 3 clinical study to assess the efficacy and safety of vimseltinib in patients with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy (prior therapy with imatinib or nilotinib allowed). The primary endpoint of the study is an objective response rate (ORR) at Week 25 in the intent-to-treat (ITT) population, as assessed by blinded independent radiologic review (IRR) per using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), versus placebo. The secondary endpoints include ORR per tumor volume score (TVS), active range of motion (ROM), physical function, stiffness, quality of life, and pain, all assessed at Week 25.

This study consists of two Parts. In Part 1, patients were randomized to receive either vimseltinib or placebo for 24 weeks. In Part 2, patients randomized to placebo in Part 1 have the option to receive vimseltinib, and all patients receive vimseltinib for a long-term period in an open-label setting.

ROMVIMZA (vimseltinib) capsules

INDICATIONS AND USAGE

ROMVIMZA is indicated for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hepatotoxicity

Cases of serious and fatal liver injury have occurred with the use of another kinase inhibitor that targets CSF1R. Serious and fatal liver injury have not been observed with ROMVIMZA.
Elevated AST and ALT can occur with ROMVIMZA.
Avoid ROMVIMZA in patients with pre-existing increased serum transaminases; total bilirubin or direct bilirubin (>ULN); or active liver or biliary tract disease, including ALP.
Monitor liver function tests prior to initiation of ROMVIMZA, twice a month for the first two months and once every 3 months for the first year of therapy and as clinically indicated thereafter. Withhold and reduce the dose, or permanently discontinue ROMVIMZA based on the severity of the hepatotoxicity.
Embryo-Fetal Toxicity:

ROMVIMZA may cause fetal harm when administered to pregnant women. Advise pregnant women on the potential risk to the fetus.
Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with ROMVIMZA and for 1 month after the last dose.
Allergic Reactions to FD&C Yellow No.5 (Tartrazine) and No. 6 (Sunset Yellow FCF):

ROMVIMZA 20 mg capsule contains FD&C Yellow No. 5 (tartrazine) which may cause allergic reactions (including bronchial asthma) in certain susceptible patients. FD&C Yellow No. 5 (tartrazine) sensitivity is frequently seen in patients who also have aspirin sensitivity.
Advise patients that ROMVIMZA 14 mg and 20 mg capsules contain FD&C Yellow No.6 (Sunset Yellow FCF), which may cause allergic reactions.
Increased Creatinine without Affecting Renal Function:

Increases in serum creatinine can occur with the use of ROMVIMZA. These increases in serum creatinine may not be associated with changes in renal function. Increases in creatinine reversed upon ROMVIMZA discontinuation. During ROMVIMZA treatment, use alternative measures that are not based on serum creatinine to assess renal function.
Adverse Reactions:

The most common (≥20%) adverse reactions, including laboratory abnormalities that occurred in patients receiving ROMVIMZA were increased AST, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased ALT.

Drug Interactions:

P-glycoprotein (P-gp) substrates: Avoid concomitant use of ROMVIMZA with P-gp substrates. If concomitant use cannot be avoided, take ROMVIMZA at least 4 hours prior to P-gp substrates.
Breast Cancer Resistance Protein (BCRP) substrates: Avoid concomitant use of ROMVIMZA with BCRP substrates.
Organic Cation Transporter 2 (OCT2) substrates: Avoid concomitant use of ROMVIMZA with OCT2 substrates.
Concomitant use of vimseltinib with P-gp substrates, BCRP substrates or OCT2 substrates may increase exposure of these substrates.
Lactation: Advise females not to breastfeed during treatment with ROMVIMZA.

Please see the accompanying full Prescribing Information.

About Tenosynovial Giant Cell Tumor (TGCT)

TGCT is a rare disease caused by a translocation in colony-stimulating factor 1 (CSF1) gene resulting in overexpression of CSF1 and recruitment of colony-stimulating factor 1 receptor (CSF1R)-positive inflammatory cells into the lesion. TGCT is a rare, non-malignant tumor that develops inside or near joints. TGCT is caused by dysregulation of the CSF1 gene leading to overproduction of CSF1. TGCT is also known as giant cell tumor of the tendon sheath (GCT-TS) or pigmented villonodular synovitis (PVNS), a diffuse-type of TGCT. Although non-malignant, these tumors can grow and cause damage to surrounding tissues and structures inducing pain, swelling, and limitation of movement of the joint. Surgery is the main treatment option; however, these tumors tend to recur, particularly in diffuse-type TGCT. If untreated or if the tumor continually recurs, damage and degeneration may occur in the affected joint and surrounding tissues, which may cause significant disability. For a subset of patients, surgical resection will potentially cause worsening functional limitation or severe morbidity, systemic treatment options are limited and a new therapeutic option for TGCT is needed.

Citius Oncology, Inc. Reports Fiscal First Quarter 2025 Financial Results and Provides Business Update

On February 14, 2025 Citius Oncology, Inc. ("Citius Oncology" or the "Company") (Nasdaq: CTOR), a specialty biopharmaceutical company focused on the development and commercialization of novel targeted oncology therapies, reported business and financial results for the fiscal first quarter ended December 31, 2024 (Press release, Citius Oncology, FEB 14, 2025, View Source [SID1234650297]).

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Fiscal First Quarter 2025 Business Highlights and Subsequent Developments

Engaged Jefferies as exclusive financial advisor to assist in evaluating strategic alternatives aimed at maximizing shareholder value, with multiple active discussions underway;
Progressed commercial readiness for the planned launch of LYMPHIR in the first half of 2025, with key initiatives including:
Manufactured sufficient inventory for launch and initial sales estimates, with additional production in process,
Secured a new permanent J-code, J9161, (Injection, denileukin diftitox-cxdl, for intravenous use, 1 microgram) for LYMPHIR, assigned by the Centers for Medicare & Medicaid Services (CMS), with an expected effective date of April 1, 2025;
Supported two investigator-initiated trials to explore LYMPHIR’s potential as an immuno-oncology combination therapy being conducted at the University of Pittsburgh Medical Center and the University of Minnesota:
Shared interim trial results with the clinical community at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference (SITC) (Free SITC Whitepaper) of University of Pittsburgh Medical Center’s Phase I trial of LYMPHIR with checkpoint inhibitor pembrolizumab.
Supported expansion of the University of Minnesota’s investigator-initiated Phase I clinical trial to evaluate the safety and efficacy of denileukin diftitox administration prior to Chimeric Antigen Receptor (CAR-T) therapies for the treatment of B-cell lymphomas with the dosing of the first patient at City of Hope cancer center.
Financial Highlights

R&D expenses were $1.3 million for the first quarter ended December 31, 2024, compared to $1.2 million for the first quarter ended December 31, 2023;
G&A expenses were $3.3 million for the first quarter ended December 31, 2024, compared to $1.5 million for the first quarter ended December 31, 2023;
Stock-based compensation expense was $1.8 million for the first quarter ended December 31, 2024, compared to $1.9 million for the first quarter ended December 31, 2023; and,
Net loss was $6.7 million, or ($0.09) per share for the first quarter ended December 31, 2024, compared to a net loss of $4.7 million, or ($0.07) per share for the first quarter ended December 31, 2023.
"During the first fiscal quarter of 2025, Citius Oncology advanced key initiatives to bring LYMPHIR to market and focused on exploring strategic options to maximize shareholder value. With FDA approval of LYMPHIR for the treatment of cutaneous T-cell lymphoma (CTCL), we are determined to deliver this much-needed therapy to patients. LYMPHIR remains the only targeted systemic therapy approved for CTCL since 2018 and the only treatment with a mechanism of action that targets the IL-2 receptor. More than 84% of CTCL patients in the Phase III trial experienced skin relief from this debilitating disease," stated Leonard Mazur, Chairman and CEO of Citius Oncology.

"To support the long-term growth potential of LYMPHIR, we engaged Jefferies as our exclusive financial advisor to evaluate strategic alternatives. Active discussions are currently underway; our goal remains to bring LYMPHIR to market expeditiously. We are making strong progress toward our planned commercial launch in the first half of 2025. The inventory for launch is ready and our market access efforts continue with the successful assignment of a new permanent J-code (J9161) by the Centers for Medicare & Medicaid Services set to take effect on April 1, 2025, and the inclusion of LYMPHIR in the NCCN guidelines. These are critical milestones that will help drive clinical adoption and reimbursement," added Mazur.

"Beyond commercial readiness, we are actively supporting two investigator-initiated trials evaluating LYMPHIR’s potential as an immuno-oncology combination therapy. Positive interim results from the University of Pittsburgh Medical Center’s Phase I trial combining LYMPHIR with pembrolizumab were shared at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference in November, highlighting its potential to enhance treatment efficacy in recurrent solid tumors. Furthermore, the University of Minnesota has expanded its Phase I trial exploring denileukin diftitox administration prior to Chimeric Antigen Receptor (CAR-T) therapies for B-cell lymphomas, with the first patient dosed at City of Hope cancer center."

"These initiatives reflect our commitment to bringing innovative cancer therapies to patients with high unmet medical needs. With the expected launch of LYMPHIR on the horizon, we remain focused on executing our commercial strategy while exploring strategic opportunities to drive long-term value," concluded Mazur.

FISCAL FIRST QUARTER 2025 FINANCIAL RESULTS:

Research and Development (R&D) Expenses

R&D expenses were $1.3 million for the first quarter ended December 31, 2024, compared to $1.2 million for the first quarter ended December 31, 2023. The increase primarily reflects costs associated with the two investigator immuno-oncology trials which are in process.

General and Administrative (G&A) Expenses

G&A expenses were $3.3 million for the first quarter ended December 31, 2024, compared to $1.5 million for the first quarter ended December 31, 2023. The increase was primarily due to costs associated with pre-commercial and commercial launch activities of LYMPHIR including market research, marketing, distribution and drug product reimbursement from health plans and payers.

Stock-based Compensation Expense

For the first quarter ended December 31, 2024, stock-based compensation expense was $1.8 million as compared to $1.9 million for the prior year. The primary reason for the decrease in stock-based compensation expense was the decrease in the weighted average grant date fair value of the options granted during the three months ended December 31, 2024 to $0.80 per share as compared to the weighted average grant date fair value of the options granted of $1.66 per share during the year ended September 30, 2024.

Net loss

Net loss was $6.7 million, or ($0.09) per share for the first quarter ended December 31, 2024, compared to a net loss of $4.7 million, or ($0.07) per share for the first quarter ended December 31, 2023. The increase in net loss was primarily due to the increase in our operating expenses.

RemeGen Announced Highly Encouraging Data from the Phase II Clinical Trial Evaluating Disitamab Vedotin plus Immunotherapy as Perioperative Regimen for Bladder Cancer

On February 14, 2025 Remegen reported that Professor Xinan Sheng from Peking University Cancer Hospital delivered the latest efficacy and safety data from the phase II clinical trial (NCT05297552, Study ID: RC48-C017) of Disitamab Vedotin (DV) in combination Toripalimab as the neoadjuvant therapy for HER2-expressing muscle-invasive bladder cancer (MIBC) in an oral presentation at the ongoing 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) held in San Francisco, USA (Press release, RemeGen, FEB 14, 2025, View Source [SID1234650296]). This marks the first public disclosure of results from a prospective clinical study investigating an ADC drug in combination with an immunotherapy as a perioperative therapy for MIBC. The pathological complete response (pCR) rate reached an impressive 63.6%, which is a breakthrough improvement compared with traditional neoadjuvant chemotherapies (36%-42%). ASCO (Free ASCO Whitepaper) GU is one of the top urologic oncology conferences that leading experts worldwide in this field attend.

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The NCT05297552 study explored the synergy between the targeted therapy and immunotherapy in the perioperative setting for MIBC. Specifically, it assessed the safety and efficacy of the novel combination therapy featuring DV, a HER2-targeting ADC drug initially developed by RemeGen Co., Ltd. (RemeGen), and Toripalimab, a PD-1 inhibitor. In May 2024, based on the NCT05297552 study, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) granted breakthrough therapy designation to DV. The preliminary results of this study were presented at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting and led to widespread attention and discussion among experts worldwide. The updated data at ASCO (Free ASCO Whitepaper) GU further validated the clinical benefits of this therapeutic approach.

In the NCT05297552 study, 47 eligible patients (10.6% with HER2 IHC 1+, 57.4% with IHC 2+, and 31.9% with IHC 3+) received the investigational neoadjuvant therapy, among whom 33 patients underwent radical cystectomy and pelvic lymph node dissection (RC + PLND). As of the data cut-off date on December 3, 2024, the study demonstrated promising efficacy and manageable safety profiles:

The pathological complete response (pCR) rate reached an impressive 63.6% (95% CI: 45.1% – 79.6%), nearly doubling that observed with traditional neoadjuvant chemotherapies (36%-42%). The pathological response rate was 75.8% (95% CI: 57.7% – 88.9%). The study showed that for patients with baseline clinical stage of T2N0, the postoperative pCR rate reached 85.7%. A pCR rate of 55.6% was also achieved in patients with other pathological subtypes of urothelial carcinoma at baseline. Patients benefited significantly regardless of PD-L1 positive/negative and regardless of HER2 expression status (IHC 1+/2+/3+), among whom the pCR rate stood at 84.6% for HER2 IHC 3+ patients.
The 12-month event-free survival (EFS) rate of all patients who underwent radical cystectomy was 92.5%, and the 18-month EFS rate was 85.9%.

The therapy exhibited a manageable safety profile. The incidence of grade 3 or higher treatment-emergent adverse events (TEAEs) was only 27.7%, notably lower than the traditional chemotherapy regimen (40%-50%), suggesting a favorable tolerability.

RemeGen is advancing research on targeted and personalized therapies for bladder cancer through indication expansion and therapy innovation of DV, aiming to provide more potent treatment options for patients worldwide. Currently, studies are in-progress to explore the feasibility of expanding DV-based regimens from later-line to front-line treatment for locally advanced or metastatic urothelial cancer. There are also plans to broaden the research of DV as a neoadjuvant therapy for MIBC to the entire perioperative period and investigate the synergy between DV and chemotherapy or other immunotherapies in treating urothelial cancer.

Imfinzi perioperative regimen improved event-free survival and overall survival across muscle-invasive bladder cancer patients regardless of complete pathology response status in post-hoc exploratory analysis of NIAGARA Phase III trial

On February 14, 2025 Astrazeneca reported results from a post-hoc exploratory subgroup analysis from the NIAGARA Phase III trial showed that Imfinzi (durvalumab), administered perioperatively in combination with neoadjuvant chemotherapy, demonstrated improvements in event-free survival (EFS) and overall survival (OS) versus neoadjuvant chemotherapy with radical cystectomy alone in patients with or without a pathologic complete response (pCR) in muscle-invasive bladder cancer (MIBC) (Press release, AstraZeneca, FEB 14, 2025, View Source [SID1234650295]). Patients were treated with four cycles of Imfinzi in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by eight cycles of Imfinzi monotherapy.

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These new data were presented today at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco, California (abstract #659).

In NIAGARA, treatment with the Imfinzi perioperative regimen improved EFS and OS versus the comparator arm both in patients who achieved pCR and those who did not. This regimen reduced the risk of disease progression, recurrence, not undergoing surgery, or death by 42% in patients who achieved pCR and by 23% in those who did not; and reduced the risk of death by 28% in patients who achieved pCR and by 16% in those who did not (see data table below for details).

The Imfinzi perioperative regimen also improved metastasis-free survival (MFS) and disease-specific survival (DSS), two secondary endpoints, versus the comparator arm in the intent-to-treat (ITT) population. This regimen reduced the risk of developing distant metastases or death by 33% and the risk of death specifically due to bladder cancer by 31% versus the comparator arm (see data table below for details).

Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, and NIAGARA Investigator and Steering Committee member, said: "These NIAGARA data confirm the compelling efficacy of the durvalumab perioperative regimen in muscle-invasive bladder cancer, and importantly, show this regimen improved outcomes regardless of whether patients achieved a pathologic complete response. This insight, together with the data showing the durvalumab perioperative regimen extended the time patients live before distant metastases develop, is favourable news for patients with muscle-invasive bladder cancer who are in need of better treatment options."

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: "NIAGARA was the first Phase III trial of a perioperative immunotherapy regimen in muscle-invasive bladder cancer to show statistically significant and clinically meaningful improvements in event-free and overall survival. The 33 per cent reduction in the risk of distant metastases, which are associated with a poorer prognosis, further reinforces the potential of perioperative Imfinzi to become a new standard of care in this setting."

These new data build on findings presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in The New England Journal of Medicine which showed NIAGARA met the primary endpoint of EFS and the key secondary endpoint of OS. In the ITT population, patients treated with the Imfinzi perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm, as well as a 25% reduction in the risk of death. There was also a 10% improvement in the pCR rate versus the comparator arm.

Summary of exploratory post-hoc analysis: NIAGARA

Patients with pCR

Patients without pCR

ITT population

Imfinzi-based regimen

(n=199)

Neoadjuvant chemotherapy (n=146)

Imfinzi-based regimen

(n=334)

Neoadjuvant chemotherapy (n=384)

Imfinzi-based regimen

(n=533)

Neoadjuvant chemotherapy (n=530)

pCRi

pCR rate (%)

37.3

27.5

p-valueii

0.0005

EFSi

EFS rate, 24 months (%)

92.1

85.8

53.3

49.5

67.8

59.8

HR (95% CI)

0.58

(0.33-1.00)

0.77

(0.63-0.95)

0.68

(0.56-0.82)

OSi

OS rate, 24 months (%)

95.5

91.1

74.1

68.9

82.2

75.2

HR (95% CI)

0.72

(0.37-1.43)

0.84

(0.66-1.07)

0.75

(0.59-0.93)

i Data cut-off: 29 April 2024

ii Nominal p-value

Summary of additional secondary endpoint outcomes (ITT): NIAGARA

Imfinzi-based regimen

(n=533)

Neoadjuvant chemotherapy

(n=530)

MFSi

MFS rate, 24 months (%)

75.1

65.1

Number of MFS events (%)

152

(28.5)

201

(37.9)

Median MFS (95% CI) (in months)

NRii

(NRii-NRii)

NRii

(48.0-NRii)

HR (95% CI)

0.67

(0.54-0.83)

DSSi

DSS rate, 24 months (%)

89.2

82.2

Number of deaths due to bladder cancer (%)

85

(15.9)

114

(21.5)

Median DSS (95% CI) (in months)

NRii

(NRii-NRii)

NRii

(NRii-NRii)

HR (95% CI)

0.69

(0.52-0.91)

i Data cut-off: 29 April 2024

ii NR, not reached

Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of Imfinzi, manageable and mostly low-grade.

Perioperative Imfinzi in combination with neoadjuvant chemotherapy was granted Priority Review in the US in December 2024 for the treatment of patients with MIBC. Regulatory applications are also currently under review in the European Union (EU), Japan and several other countries based on the NIAGARA trial.

Notes

Muscle-invasive bladder cancer
Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year.1 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.2 Approximately one in four patients with bladder cancer has evidence of the tumour invading the muscle wall of the bladder (without distant metastases), known as MIBC.3-4

In MIBC, a curative-intent setting, approximately 117,000 patients are treated with the current standard of care, which includes neoadjuvant chemotherapy and radical cystectomy.5-6 However, even after cystectomy, approximately 50% of patients experience disease recurrence and have a poor prognosis.6 Treatment options that prevent disease recurrence after surgery are critically needed in this curative-intent setting.

NIAGARA
NIAGARA is a randomised, open-label, multi-centre, global Phase III trial evaluating perioperative Imfinzi as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomised to receive Imfinzi plus neoadjuvant chemotherapy prior to cystectomy followed by Imfinzi, or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting.

The trial is being conducted at 192 centres across 22 countries including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS and pCR, the latter defined as the proportion of patients with no detectable cancer cells (T0N0M0) at the time of cystectomy. Key secondary endpoints are OS and safety.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.

In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU.

Imfinzi is also approved in combination with chemotherapy (carboplatin and paclitaxel) followed by Imfinzi monotherapy in primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) in the US. In the EU, Imfinzi plus chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient (pMMR) advanced or recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by Imfinzi alone is approved for patients with dMMR disease. In Japan, Imfinzi plus chemotherapy followed by Imfinzi monotherapy has also been approved as 1st-line treatment in primary advanced or recurrent endometrial cancer, and Imfinzi plus chemotherapy followed by Imfinzi and Lynparza has been approved for patients with pMMR disease.

Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours.