On September 9, 2025 Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., reported new data from the REZILIENT1 and REZILIENT2 trials of zipalertinib, an oral EGFR tyrosine kinase inhibitor, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Taiho, SEP 9, 2025, View Source [SID1234655887]). These data will be presented at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer as mini oral presentations on September 9 during the "MA08 – Common and Uncommon EGFR Mutations, New Treatments in the Horizon" session, from 11:30 a.m. – 12:45 p.m. CEST.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A mini oral presentation will highlight updated data from the pivotal Phase 2b REZILIENT1 trial of zipalertinib, focused on patients with NSCLC harboring EGFR ex20ins mutations, who have been previously treated with amivantamab.1

A second mini oral presentation will highlight Phase 2b preliminary efficacy and safety results from the ongoing, uncommon non-ex20ins EGFR mutations cohort of the REZILIENT2 trial of zipalertinib in patients with advanced or metastatic NSCLC harboring ex20ins and uncommon non-ex20ins EGFR mutations.2

"We’re pleased to share longer-term follow-up data from the REZILIENT1 study of zipalertinib for patients with NSCLC harboring EGFR ex20ins mutations who have been previously treated with amivantamab," said Zofia Piotrowska, MD, Associate Professor of Medicine, Harvard Medical School and lung cancer clinical oncologist at the Mass General Cancer Center. "Despite recent treatment advancements, a significant medical need exists for this patient population, underscoring the importance of these data."

"Uncommon non-exon 20 insertion EGFR mutations represent a significant clinical challenge, as they exhibit variable and often suboptimal responses to currently approved tyrosine kinase inhibitors," said Hibiki Udagawa, MD, PhD, thoracic medical oncologist, National Cancer Hospital East, Japan. "We are pleased to present the interim data from the uncommon non-ex20ins EGFR mutations cohort from the REZILIENT2 trial, potentially demonstrating the need for novel, targeted therapeutic approaches for this patient population."

Authors reported results from the REZILIENT1 study of zipalertinib from the cohort of NSCLC patients with EGFR ex20ins mutations who received prior amivantamab therapy1

Summary of Efficacy – by Blinded Independent Central Review (BICR):
As of the June 2025 data cutoff, 84 post-amivantamab patients were enrolled in REZILIENT1 and received at least one dose of 100 mg zipalertinib. Patients had received a median of 3 prior lines of therapy, and 54.8% of patients had a history of brain metastases.

With follow-up of more than 9 months, zipalertinib demonstrated:

In all patients (n=84), confirmed objective response rate (ORR) was 27.4% with median duration of response (mDOR) of 8.5 months, and the disease control rate (DCR) was 84.5%.

In patients with prior amivantamab only (n=54), ORR was 31.5% with mDOR of 9.5 months, and the DCR was 87.0%.

In patients with prior amivantamab and other ex20ins-targeted therapy (n=30), ORR was 20.0% with mDOR of 8.3 months, and the DCR was 80.0%.

In patients with brain metastases who received prior amivantamab only (n=31), the systemic ORR was 29%.
Summary of Safety and Tolerability
The safety analysis population included all post-amivantamab patients in REZILIENT1 who received at least one dose of 100 mg zipalertinib (n=84). The results showed that zipalertinib 100 mg twice daily demonstrated a manageable safety profile in patients who progressed on prior chemotherapy and amivantamab with no new safety signals.

The most common treatment-emergent adverse events (TEAEs, all-grade) were paronychia (41.7%), anemia (38.1%), rash (34.5%), nausea (28.6%), diarrhea (22.6%), dry skin (21.4%), dermatitis acneiform (21.4%) and dyspnea (20.2%).

The most common grade ≥3 TEAEs were anemia (15.5%), pneumonia (10.7%), dyspnea (6.0%), rash (3.6%), diarrhea (2.4%) and stomatitis (2.4%).

Authors reported results from the REZILIENT2 study of zipalertinib from the cohort of patients with NSCLC harboring uncommon non-exon 20 insertion EGFR mutations2

Summary of Preliminary Efficacy –by Investigator
As of the March 2025 data cutoff, 40 patients were enrolled in the REZILIENT2 Cohort D and received zipalertinib 100 mg orally twice daily. Previously treated patients had received a median of 2 prior lines of therapy, and 30% of all patients enrolled, including treatment-naïve, had a history of brain metastases.

As of the data cut-off, zipalertinib demonstrated:

In the overall efficacy population (n=40), confirmed ORR was 30% with a mDOR of 7.75 months, and the disease control rate (DCR) was 70%.
In the treatment-naïve population (n=8), ORR was significantly higher (62.5%) compared to the previously treated patient population (n=32, ORR 21.9%).
Summary of Preliminary Safety and Tolerability
The safety analysis population included all REZILIENT2 patients in Cohort D who received at least one dose of 100 mg zipalertinib (n=40). The results showed that zipalertinib 100 mg twice daily demonstrated a manageable safety and tolerability profile with no new safety signals.

The most common treatment-related adverse events (TRAEs, all-grade) were paronychia (47.5%), dermatitis acneiform (37.5%), stomatitis (32.5%), anemia (30.0%), diarrhea (22.5%), rash (20.0%), and dry skin (15.0%). The majority of TRAEs were grade 1 or 2.

The most common grade ≥3 TRAEs were paronychia (5.0%), pneumonitis and anemia (5.0%).

About REZILIENT1
REZILIENT1 (Researching Zipalertinib In EGFR Non-Small Cell Lung Cancer Tumors) is a Phase 1/2 clinical trial (NCT04036682) to evaluate efficacy and safety of zipalertinib in adult patients with advanced or metastatic NSCLC harboring EGFR ex20ins mutations who have received prior therapy. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoints were ORR and DOR as assessed by blinded independent central review (ICR) per RECIST v1.1. Adverse events were characterized and graded according to Common Terminology Criteria for Adverse Events (CTCAE v5.0).

About REZILIENT2
REZILIENT2 is a Phase 2b clinical trial (NCT05967689), evaluating zipalertinib in patients with locally advanced/metastatic NSCLC harboring ex20ins and uncommon single or compound EGFR mutations. Patients were treated with oral zipalertinib 100 mg twice daily. The primary endpoint was ORR and confirmed per investigator-assessed Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 and the secondary endpoints included DOR, DCR and safety.

About Zipalertinib
Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with ex20ins mutations, while sparing wild-type EGFR. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib has received Breakthrough Therapy Designation from the FDA. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

On September 9, 2025 Dizal (SSE:688192), a biopharmaceutical company committed to developing novel medicines for the treatment of cancer and immunological diseases, reported the presentation of new findings on its leading assets, ZEGFROVY (sunvozertinib) and golidocitinib, in non-small cell lung cancer (NSCLC) at the 2025 World Conference on Lung Cancer (WCLC), held September 6–9 in Barcelona, Spain (Press release, Dizal Pharma, SEP 9, 2025, View Source [SID1234655886]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

ZEGFROVY: Targeting EGFR exon20ins and a wide spectrum of EGFR mutations

The latest data from the multinational pivotal WU-KONG1 Part B (WU-KONG1B) study for ZEGFROVY were presented in an oral session at the conference and simultaneously published in the Journal of Clinical Oncology. Based on results from WU-KONG1B, ZEGFROVY received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2025 as the only targeted oral therapy for NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations (exon20ins).

ZEGFROVY demonstrated a favorable benefit/risk profile in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins. The study showed robust and durable antitumor activity with a manageable safety profile. (#MA08.01).

In addition to the oral presentation, multiple studies of ZEGFROVY were presented at the WCLC, highlighting its potential across a broad range of NSCLC patients, including those with EGFR exon20ins across all lines of therapy, uncommon EGFR and HER2 mutations, EGFR-sensitive mutation and co-mutations, and EGFR mutations resistant to EGFR TKIs. Both monotherapy and combination regimens were evaluated.

In EGFR exon20ins NSCLC, ZEGFROVY demonstrated promising antitumor efficacy and a tolerable safety profile across first- and second- line, as well as adjuvant and neoadjuvant treatment settings.

ZEGFROVY combined with anlotinib achieved an objective response rate (ORR) of over 80% and a disease control rate (DCR) of 100% in treatment-naïve EGFR exon20ins NSCLC (#P3.12.43).
In previously treated patients, ZEGFROVY combined with bevacizumab achieved a DCR of 100%, with target tumor lesion shrinkage observed in 85.7% of patients. With a median follow-up of 15.2 months, the median duration of response (DoR) was 19.1 months, and three patients (3/14) remained in response at the data cut-off (#P2.10.13).
Real-world cases supported the potential of ZEGFROVY in early- and advanced- stage NSCLC patients with EGFR exon20ins.

As a neoadjuvant therapy, ZEGFROVY showed encouraging clinical benefit, with all 3 patients achieving an obvious partial response (PR) before surgery. (#EP.07.49).
In the adjuvant setting, ZEGFROVY showed sustained efficacy and tolerable safety profiles, helping patients successfully pass the 1-year after surgery, a peak period for disease recurrence (#EP.07.55).
In the first-line maintenance setting, ZEGFROVY showed sustained efficacy and safety in lung adenocarcinoma patients who were intolerant to immunotherapy and chemotherapy (#EP.12.47).
In NSCLC patients harboring uncommon EGFR mutations, ZEGFROVY combined with anlotinib demonstrated promising efficacy, including one patient who achieved complete remission of intracranial lesions (#P3.12.43). In a separate real-world case series, ZEGFROVY exhibited clinical efficacy in advanced NSCLC with HER2 exon20ins, with tumor shrinkage obviously observed post-prior treatment failures (#EP.12.46).

In treatment-naïve NSCLC patients with EGFR-sensitive mutation and co-mutations, ZEGFROVY in combination with anlotinib achieved an ORR of 77.8% and a DCR of 100% (#P3.12.22). In NSCLC patients with EGFR mutations who failed prior EGFR-TKI therapies, ZEGFROVY, both as monotherapy (#EP.12.43) and in combination with chemotherapy (#P3.12.47), was well tolerated and demonstrated encouraging antitumor activity.

Golidocitinib: Janus kinase 1 (JAK1) only inhibitor Plus Anti-PD-1 in Anti-PD-1 Treated Advanced NSCLC

Resistance to first-line immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) leads to limited treatment options and poor prognosis. Preclinical and early clinical data have shown synergistic effects between JAK inhibitors and anti-PD-1, suggesting a promising therapeutic strategy in this population. Golidocitinib in combination with anti-PD-1 was being evaluated in immune-resistant NSCLC patients. The study showed a well-tolerated profile, with no DLTs observed in the dose-escalation phase. Ongoing enrollment and data collection will provide deeper insights into clinical utility of golidocitinib (#P1.11.74).

Dr. Xiaolin Zhang, CEO of Dizal, remarked, "Dizal is advancing therapies for patients with NSCLC across EGFR exon 20 insertion, uncommon and EGFR-sensitizing mutations to address significant unmet medical needs. Through scientific innovation, we aim to deliver safe, effective and transformative treatments to patients worldwide."

On September 9, 2025 Tagworks Pharmaceuticals BV ("Tagworks"), a clinical-stage precision oncology company using its proprietary Click-to-Release treatment platform to develop a new standard of care for patients suffering from solid tumors, reported the third dose level has been initiated in the ongoing Phase 1 clinical trial evaluating TGW101, a first-in-class antibody-drug conjugate (ADC) targeting tumor associated glycoprotein 72 (TAG-72) with a monomethyl auristatin E (MMAE) payload, in patients with advanced solid tumors (Press release, Tagworks Pharmaceuticals, SEP 9, 2025, View Source [SID1234655885]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased to report continued progress in our Phase 1 clinical trial of TGW101 which reflects our strong operational execution and commitment to advancing our pioneering Click-to-Release technology," said Ken Mills, Chief Executive Officer of Tagworks. "The Safety Oversight Committee’s decision to proceed to the third dose level highlights TGW101’s favorable safety profile to date. We are encouraged by the potential of TGW101’s highly differentiated profile to address significant unmet needs in the treatment of advanced solid tumors, while overcoming limitations seen with other ADC therapies. We look forward to sharing preliminary data from the study, including safety, pharmacokinetics, and potential early signs of clinical activity, in early to mid-2026."

The ongoing Phase 1 trial is a multicenter, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of TGW101 in patients with relapsed or refractory solid tumors. The primary objectives are to determine the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and dose regimen for cohort expansion.

To date, the trial has initiated three dose levels following favorable safety reviews by the Safety Oversight Committee (SOC). Up to seven dose levels are currently planned, and the maximum dose to be evaluated may be updated based on evolving clinical safety and pharmacokinetic data. The study aims to enroll up to 50 patients across sites in the United States, with potential expansion to additional regions.

Tagworks expects to share preliminary safety and pharmacokinetic data, along with any early signals of efficacy, in early to mid-2026.

About TGW101
TGW101 is an antibody-drug conjugate (ADC) targeting TAG-72, a non-internalizing marker found on the surface of many solid tumor cells. TGW101 consists of a TAG-72-binding diabody conjugated with monomethyl auristatin E (MMAE) toxin. TGW101 is administered intravenous (IV) first and allowed to bind to TAG-72 in the tumor. Then a small molecule trigger is administered IV, resulting in selective chemical cleavage of the linker of the tumor-bound TGW101, release of the MMAE in the extracellular tumor microenvironment and diffusion into surrounding tumor cells. TGW101 is being studied in an open-label, multicenter, Phase 1 dose-escalation clinical trial designed to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced solid tumors.

On September 9, 2025 Citius Oncology, Inc. ("Citius Oncology") (Nasdaq: CTOR), the oncology-focused subsidiary of Citius Pharmaceuticals, Inc. ("Citius Pharma") (Nasdaq: CTXR), a late-stage biopharmaceutical company developing and commercializing first-in-class critical care products, reported that it has entered into a securities purchase agreement with a single institutional investor to purchase 5,142,858 shares of common stock in a registered direct offering (Press release, Citius Oncology, SEP 9, 2025, View Source [SID1234655884]). In a concurrent private placement, the Company also agreed to issue unregistered warrants to purchase up to an aggregate of 5,142,858 shares of common stock. The combined effective offering price for each share of common stock and accompanying warrant is $1.75. The warrants will have an exercise price of $1.84 per share, will be exercisable six months from the date of issuance, and will expire on the five and one-half year anniversary from the date of issuance.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The gross proceeds to the Company from the registered direct offering and concurrent private placement are estimated to be approximately $9.0 million before deducting placement agent fees and other estimated offering expenses payable by the Company. The offering is expected to close on or about September 10, 2025, subject to the satisfaction of customary closing conditions.

Maxim Group LLC is acting as sole placement agent in connection with the offering.

The shares of common stock described above are being offered pursuant to a registration statement on Form S-3 (File No. 333-289979), which was filed with the U.S. Securities and Exchange Commission ("SEC") on September 2, 2025, and was declared effective by the SEC on September 4, 2025. The offering of shares of common stock will be made only by means of a prospectus supplement, forming a part of the effective registration statement. A prospectus supplement relating to the shares of common stock will be filed with the SEC. Electronic copies of the prospectus relating to this offering, when available, may also be obtained from Maxim Group LLC, 300 Park Avenue, 16th Floor, New York, New York 10022, Attention: Syndicate Department, by telephone at (212) 895-3745 or by email at [email protected]. The warrants to be issued in the concurrent private placement and the shares issuable upon exercise of such warrants were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and have not been registered under the Act or applicable state securities laws.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other 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 other jurisdiction.

On September 9, 2025 Johnson & Johnson (NYSE:JNJ) reported the U.S. Food and Drug Administration (FDA) approved INLEXZO (gemcitabine intravesical system), a new, potentially practice-changing approach for treating patients with certain types of bladder cancer, addressing the need for additional options following unsuccessful BCG therapy and for patients refusing or ineligible for bladder removal surgery (radical cystectomy) (Press release, Johnson & Johnson, SEP 9, 2025, View Source [SID1234655883]). INLEXZO, previously referred to as TAR-200, is indicated for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

INLEXZO is designed for patients seeking bladder preservation and is the first and only intravesical drug releasing system (iDRS) to provide extended local delivery of a cancer medication into the bladder. INLEXZO remains in the bladder for three weeks per treatment cycle for up to 14 cycles.1 A healthcare professional places INLEXZO into the bladder using a co-packaged urinary catheter and stylet to insert it into the bladder.1 INLEXZO is placed in an outpatient setting in a few minutes, without the need for general anesthesia or further monitoring immediately post-insertion within the healthcare provider’s office.1

"When we acquired this novel therapy in 2019, our ambition was to give patients with bladder cancer a renewed sense of hope and belief," said Jennifer Taubert, Executive Vice President, Worldwide Chairman, Innovative Medicine, Johnson & Johnson. "In an area that has seen little progress for more than 40 years, INLEXZO delivers a first-of-its-kind breakthrough innovation with a bright future ahead."

The approval is supported by data from the SunRISe-1 (NCT04640623) single arm, open-label Phase 2b clinical study.1 Results show 82 percent of patients with BCG-unresponsive NMIBC treated with INLEXZO achieved a complete response (CR), meaning no signs of cancer were found after treatment (95 percent confidence interval [CI], 72, 90).1 This high response rate demonstrated strong durability, and 51 percent of these patients maintained a complete response for at least one year.1

In the SunRISe-1 clinical trial supporting this approval, the most common adverse reactions (≥15 percent) including laboratory abnormalities, were urinary frequency, urinary tract infection, dysuria, micturition urgency, decreased hemoglobin, increased lipase, urinary tract pain, decreased lymphocytes, hematuria, increased creatinine, increased potassium, increased aspartate aminotransferase (AST), decreased sodium, bladder irritation, and increased alanine transaminase (ALT).1

"I see many patients that ultimately become BCG-unresponsive and often face life-altering bladder removal. These patients now may be ideal candidates for newly approved INLEXZO," said Sia Daneshmand, M.D., TAR-200 SunRISe-1 principal investigator, and Professor of Urology, Director of Urologic Oncology at the Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California.* "In my experience, INLEXZO is well-tolerated and delivers clinically meaningful results. This will change the way we treat appropriate patients that haven’t responded to traditional therapy."

"We are proud of the science that has brought us to this historic moment," said John Reed, M.D., Ph.D., Executive Vice President, R&D, Innovative Medicine, Johnson & Johnson. "INLEXZO is a novel therapy with powerful efficacy and demonstrated safety profile. As the only major healthcare company that hosts both pharmaceuticals and medical devices, we leveraged the speed and scale of Johnson & Johnson to accelerate innovation and deliver this important therapy to patients."

"At BCAN, our mission has always been to advocate for better todays and more tomorrows for everyone impacted by bladder cancer. This approval represents the kind of progress that brings new options to a community that urgently needs them," said Meri-Margaret Deoudes, CEO, Bladder Cancer Advocacy Network (BCAN).** "Patients with bladder cancer need guidance and collaboration with providers to navigate bladder-sparing treatment options, including newly approved treatments like INLEXZO, so they can move forward feeling well-informed and confident."

Leading to today’s approval, the FDA granted INLEXZO Breakthrough Therapy Designation (BTD), Real-Time Oncology Review (RTOR), and Priority Review.

Johnson & Johnson is committed to helping patients access our treatments. Once a patient and their doctor have decided that INLEXZO is right for the patient, J&J withMe provides a simple, comprehensive patient support program offering cost support, a dedicated Care Navigator and educational resources, at no cost to the patient.

About SunRISe-1, Cohort 2
SunRISe-1 (NCT04640623), Cohort 2, was a single arm, open-label Phase 2b clinical study that evaluated the safety and efficacy of INLEXZO monotherapy for BCG-unresponsive NMIBC patients with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for, or elected not to undergo, radical cystectomy. The primary endpoint for Cohort 2 was complete response (CR) rate at any time point, and secondary endpoints include duration of response (DOR).

About Non-Muscle Invasive Bladder Cancer (NMIBC) and the Current Standard of Care
Non-muscle invasive bladder cancer (NMIBC) is a type of non-invasive bladder cancer that can be classified as low, intermediate, or high risk depending on the presence of characteristics including tumor size, presence of multiple tumors, and carcinoma in situ (CIS).2 NMIBC with CIS makes up approximately 10 percent of patients with NMIBC.3 The current standard of care for NMIBC is Bacillus Calmette-Guérin (BCG), which is a weakened form of the bacteria found in tuberculosis treatment. Though effective, some patients become unresponsive to it and may experience challenges.4,5 Radical cystectomy is currently recommended for NMIBC patients who fail BCG therapy; it is a life-altering surgery with a high degree of morbidity and adverse impact on life, and has a post-surgery mortality rate of three to eight percent.6,7 Given that NMIBC typically affects older patients, many may be unwilling or unfit to undergo radical cystectomy.

About INLEXZO
INLEXZO is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. INLEXZO is an intravesical system enabling extended release of gemcitabine into the bladder. It is placed in a few minutes without general anesthesia or further monitoring immediately post-insertion within the healthcare provider’s office. For more information, visit INLEXZO.com.

The safety and efficacy of INLEXZO is being evaluated in clinical trials in patients with MIBC in SunRISe-4, and NMIBC in SunRISe-1, SunRISe-3, and SunRISe-5.

INLEXZO INDICATION AND IMPORTANT SAFETY INFORMATION

INDICATION
INLEXZO (gemcitabine intravesical system) is indicated for the treatment of adult patients with Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
INLEXZO is contraindicated in patients with:

Perforation of the bladder.
Prior hypersensitivity reactions to gemcitabine or any component of the product.
WARNINGS AND PRECAUTIONS

Risks in Patients with Perforated Bladder
INLEXZO may lead to systemic exposure to gemcitabine and to severe adverse reactions if administered to patients with a perforated bladder or to those in whom the integrity of the bladder mucosa has been compromised.

Evaluate the bladder before the intravesical administration of INLEXZO and do not administer to patients with a perforated bladder or mucosal compromise until bladder integrity has been restored.

Risk of Metastatic Bladder Cancer with Delayed Cystectomy
Delaying cystectomy in patients with BCG-unresponsive CIS could lead to development of muscle invasive or metastatic bladder cancer, which can be lethal. The risk of developing muscle invasive or metastatic bladder cancer increases the longer cystectomy is delayed in the presence of persisting CIS.

Of the 83 evaluable patients with BCG-unresponsive CIS treated with INLEXZO in Cohort 2 of SunRISe-1, 7 patients (8%) progressed to muscle invasive (T2 or greater) bladder cancer. Three patients (3.5%) had progression determined at the time of cystectomy. The median time between determination of persistent or recurrent CIS or T1 and progression to muscle invasive disease was 94 days.

Magnetic Resonance Imaging (MRI) Safety
INLEXZO can only be safely scanned with MRI under certain conditions. Refer to section 5.3 of the USPI for details on conditions.

Embryo-Fetal Toxicity
Based on animal data and its mechanism of action, INLEXZO can cause fetal harm when administered to a pregnant woman if systemic exposure occurs. In animal reproduction studies, systemic administration of gemcitabine was teratogenic, embryotoxic, and fetotoxic in mice and rabbits.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after final removal of INLEXZO. Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after final removal of INLEXZO.

ADVERSE REACTIONS
Serious adverse reactions occurred in 24% of patients receiving INLEXZO. Serious adverse reactions that occurred in >2% of patients included urinary tract infection, hematuria, pneumonia, and urinary tract pain. Fatal adverse reactions occurred in 1.2% of patients who received INLEXZO, including cognitive disorder.

The most common (>15%) adverse reactions, including laboratory abnormalities, were urinary frequency, urinary tract infection, dysuria, micturition urgency, decreased hemoglobin, increased lipase, urinary tract pain, decreased lymphocytes, hematuria, increased creatinine, increased potassium, increased AST, decreased sodium, bladder irritation, and increased ALT.

USE IN SPECIFIC POPULATIONS

Pregnancy
There are no available data on the use of INLEXZO in pregnant women to inform a drug-associated risk.

Please see Embryo-Fetal Toxicity for risk information related to pregnancy.

Lactation
Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 1 week after final removal of INLEXZO.

Females and Males of Reproductive Potential
Pregnancy Testing – Verify pregnancy status in females of reproductive potential prior to initiating INLEXZO.

Contraception – Please see Embryo-Fetal Toxicity for information regarding contraception.

Infertility (Males) – Based on animal studies, INLEXZO may impair fertility in males of reproductive potential. It is not known whether these effects on fertility are reversible.

Geriatric Use
Of the patients given INLEXZO monotherapy in Cohort 2 of SunRISe-1, 72% were 65 years of age or older and 34% were 75 years or older. There were insufficient numbers of patients <65 years of age to determine if these patients respond differently to patients 65 years of age and older.

Please read full Prescribing Information and Instructions for Use for INLEXZO.