On October 2, 2024 TerSera Therapeutics LLC reported the presentation of new real-world analyses on the treatment patterns of goserelin in women with breast cancer (Press release, TerSera Therapeutics, OCT 2, 2024, View Source [SID1234647010]). The data were presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Quality Care Symposium, held September 27th and 28th in San Francisco, CA.

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The goal of this study was to demonstrate the characteristics of US patients with a diagnosis of breast cancer treated with either goserelin 3.6 mg or 10.8 mg and analyze goserelin treatment patterns using real-world evidence (RWE). This retrospective study used US electronic health record data through TriNetX, a global healthcare research network. The study included adult women with a history of breast cancer and with ≥2 prescriptions of goserelin between January 2017 – December 2022. Follow-up occurred until March 15, 2024.

Overall, 3,620 patients were identified: 2,870 treated with goserelin 3.6 mg, 410 with goserelin 10.8 mg, and 340 who switched from goserelin 3.6 mg to 10.8 mg. Patient demographics, treatment adherence, and healthcare resource utilization (HCRU) were examined and summarized using descriptive analytics.

"For young women with hormone-sensitive breast cancer at high-risk of relapse, suppression of ovarian function is an essential component of their long-term treatment plan," said Lonnie Brent, Pharm.D., Senior Vice President, Medical and Scientific Affairs for TerSera. "This real-world evidence presented at the ASCO (Free ASCO Whitepaper) Quality Care Symposium increases our understanding of the current treatment patterns for young women with breast cancer receiving goserelin."

U.S. INDICATIONS

ZOLADEX 3.6 mg and ZOLADEX 10.8 mg are indicated for:

Management of locally confined Stage T2b-T4 (Stage B2-C) carcinoma of the prostate in combination with flutamide. Treatment with ZOLADEX and flutamide should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy.
Palliative treatment of advanced carcinoma of the prostate.
ZOLADEX 3.6 mg is also indicated for:

Management of endometriosis, including pain relief and reduction of endometriotic lesions for the duration of therapy. Experience with ZOLADEX for the management of endometriosis has been limited to women 18 years of age and older treated for 6 months.
Use as an endometrial-thinning agent prior to endometrial ablation for dysfunctional uterine bleeding.
Palliative treatment of advanced breast cancer in pre- and perimenopausal women.
IMPORTANT SAFETY INFORMATION

Anaphylactic reactions to ZOLADEX have been reported in the medical literature. ZOLADEX is contraindicated in patients with a known hypersensitivity to GnRH, GnRH agonist analogues, or any of the components in ZOLADEX.

ZOLADEX is contraindicated during pregnancy unless used for palliative treatment of advanced breast cancer. ZOLADEX can cause fetal harm when administered to a pregnant woman. If used during pregnancy, the patient should be apprised of the potential hazard to the fetus. There is an increased risk for pregnancy loss due to expected hormonal changes that occur with ZOLADEX treatment. ZOLADEX should not be given to women with undiagnosed abnormal vaginal bleeding.

Pregnancy must be excluded for use in benign gynecological conditions. Women should be advised against becoming pregnant while taking ZOLADEX. Effective nonhormonal contraception must be used by all premenopausal women during ZOLADEX therapy and for 12 weeks following discontinuation of therapy.

Transient worsening of tumor symptoms, or the occurrence of additional signs and symptoms of breast cancer, may occasionally develop during the first few weeks of treatment. Some patients may experience a temporary increase in bone pain. Monitor patients at risk for complications of tumor flare.

Hyperglycemia and an increased risk of developing diabetes or worsening of glycemic control in patients with diabetes have been reported in men receiving GnRH agonists like ZOLADEX. Monitor blood glucose levels and glycosylated hemoglobin (HbA1c) periodically and manage according to current clinical practice.

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists like ZOLADEX in men. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Hypercalcemia has been reported in some breast cancer patients with bone metastases after starting treatment with ZOLADEX. If hypercalcemia does occur, appropriate treatment measures should be initiated.

Hypersensitivity, antibody formation and acute anaphylactic reactions have been reported with GnRH agonist analogues.

ZOLADEX may cause an increase in cervical resistance. Therefore, caution is recommended when dilating the cervix for endometrial ablation.

GnRH agonists may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes.

Injection site injury and vascular injury including pain, hematoma, hemorrhage and hemorrhagic shock, requiring blood transfusions and surgical intervention, have been reported with ZOLADEX. Extra care should be taken when administering ZOLADEX to patients with low BMI and/or to patients receiving full dose anticoagulation.

Depression may occur or worsen in women receiving GnRH agonists.

Treatment with ZOLADEX may be associated with a reduction in bone mineral density over the course of treatment. Data suggest a possibility of partial reversibility. In women, current available data suggest that recovery of bone loss occurs on cessation of therapy in the majority of patients.

In women, the most frequently reported adverse reactions were related to hypoestrogenism. The adverse reaction profile was similar for women treated for breast cancer, dysfunctional uterine bleeding, and endometriosis.

The most commonly reported adverse reactions with ZOLADEX in clinical trials for endometriosis were: hot flashes (96%), vaginitis (75%), headache (75%), decreased libido (61%), emotional lability (60%), depression (54%), sweating (45%), acne (42%), breast atrophy (33%), seborrhea (26%), and peripheral edema (21%).

The most commonly reported adverse reactions with ZOLADEX in clinical trials for endometrial thinning were: vasodilation/hot flashes (57%), headache (32%), sweating (16%), and abdominal pain (11%).

The most commonly reported adverse reactions with ZOLADEX in breast cancer clinical trials were hot flashes (70%), decreased libido (47.7%), tumor flare (23%), nausea (11%), edema (5%), and malaise/fatigue/lethargy (5%). Injection site reactions were reported in less than 1% of patients.

For ZOLADEX 3.6 mg: Hot flashes (62%), sexual dysfunction (21%), decreased erections (18%), lower urinary tract symptoms (13%), lethargy (8%), pain (worsened in the first 30 days) (8%), edema (7%), upper respiratory infection (7%), rash (6%), and sweating (6%).

For ZOLADEX 10.8 mg: Hot flashes (64%), pain (general) (14%), gynecomastia (8%), pelvic pain (6%), and bone pain (6%).

In the locally advanced carcinoma of the prostate clinical trial, additional adverse event data were collected for the combination therapy with radiation group during both the hormonal treatment and hormonal treatment plus radiation phases of this study. Adverse experiences (incidence >5%) in both phases of this study were hot flashes (46%), diarrhea (40%), nausea (9%), and skin rash (8%). Treatment with ZOLADEX and flutamide did not add substantially to the toxicity of radiation treatment alone.

Please see Full Prescribing Information for ZOLADEX 3.6 mg and ZOLADEX 10.8 mg.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit fda.gov/safety/medwatch or call 1-800-FDA-1088. You can also contact TerSera Therapeutics at 1-844-334-4035 or [email protected].

About HR-positive breast cancer

Breast cancer is the second most commonly diagnosed cancer and one of the leading causes of cancer-related deaths worldwide. 2 In the United States, over 310,000 women will be diagnosed with breast cancer this year; 40,000 will be under the age of 50. 3 Approximately 75% of diagnosed cases in women under age 50 are considered to be hormone positive (HR+) breast cancer. Compared to older women, young women generally face more aggressive cancers and lower survival rates.4,5 Recent studies have shown that breast cancer before age 40 differs biologically from the cancer faced by older women.6

About ZOLADEX (goserelin implant)

ZOLADEX is an injectable luteinizing hormone-releasing hormone agonist (LHRHa) used to treat prostate cancer, breast cancer, and certain benign gynecological disorders. First approved in the U.S. in 1989, ZOLADEX is available as a 3.6 mg implant dosed every 28 days or as a 10.8 mg implant dosed every 12 weeks. Worldwide, ZOLADEX 3.6 mg is approved for use in breast cancer in 125 countries. ZOLADEX 10.8 mg is approved for use in breast cancer in over 60 countries.

On October 2, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported a clinical trial collaboration agreement with AstraZeneca (LSE/STO/Nasdaq: AZN) to evaluate casdatifan (AB521), Arcus’s investigational HIF-2a inhibitor, in combination with volrustomig, AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, in patients with ccRCC (Press release, Arcus Biosciences, OCT 2, 2024, View Source [SID1234647009]).

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"We believe casdatifan has best-in-class potential, based on the observed PK and PD profiles and the emerging clinical data from our ARC-20 study in patients with ccRCC," said Terry Rosen, Ph.D., chief executive officer of Arcus. "This agreement will enable Arcus and AstraZeneca to collaborate and assess the potential for the novel combination of casdatifan with volrustomig to improve outcomes for patients with ccRCC."

"Renal cell carcinoma is a known CTLA-4-responsive tumor type, and our first-in-human study with volrustomig monotherapy demonstrated encouraging efficacy in first-line advanced ccRCC," said Cristian Massacesi, chief medical officer and oncology chief development officer, AstraZeneca. "We are excited by the potential to build on this by combining HIF-2a inhibition with volrustomig to drive deeper and more durable responses for patients."

As part of this collaboration, AstraZeneca will sponsor and operationalize a study to evaluate the safety and early efficacy of the casdatifan plus volrustomig combination in patients with advanced ccRCC.

This is the second clinical collaboration between Arcus and AstraZeneca. In 2020, the companies announced a clinical collaboration for PACIFIC-8, a registrational Phase 3 study of domvanalimab, an Fc-silent anti-TIGIT antibody, added to backbone global standard-of-care durvalumab, an anti-PD-L1 antibody, in patients with unresectable Stage III non-small cell lung cancer.

Under the Gilead and Arcus collaboration agreement, Gilead has the right to opt-in to development and commercialization for casdatifan after Arcus’s delivery of a qualifying data package.

About Casdatifan (AB521)

Casdatifan is a small-molecule inhibitor of HIF-2a, a transcription factor involved in oxygen sensing in multiple organs as well as in tumors. Clear cell RCC is almost universally associated with HIF-2a dysregulation as a result of genetic abnormalities in the VHL pathway. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2a-mediated expression of a wide array of proteins involved in cancer cell proliferation and survival, treatment resistance and angiogenesis. Casdatifan is being evaluated in ARC-20, a Phase 1/1b study in cancer patients, and STELLAR-009, a Phase 1b/2 study in combination with zanzalintinib in patients with advanced solid tumors, including ccRCC.

Casdatifan and domvanalimab are investigational molecules. Approval from any regulatory authority for any use of these molecules globally has not been received, and their safety and efficacy have not been established.

About RCC

According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 81,600 Americans will be diagnosed with kidney cancer in 2024. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 15%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.

On October 2, 2024 Johnson & Johnson (NYSE: JNJ) reported the results of a landmark real-world, head-to-head study showing that ERLEADA (apalutamide) provided a statistically significant overall survival benefit at 24 months compared to enzalutamide in patients with metastatic castration-sensitive prostate cancer (mCSPC). Presented at the 6th European Congress of Oncology Pharmacy (ECOP) in Lisbon, Portugal, on October 2 (Abstract #P31), this study of nearly 4,000 patients represents the largest real-world, head-to-head analysis of these two androgen receptor pathway inhibitors (ARPIs) in mCSPC (Press release, Johnson & Johnson, OCT 2, 2024, View Source [SID1234647008]).

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The study applied U.S. Food and Drug Administration (FDA) real-world evidence guidance and employed robust methodology, data sources and a large, diverse cohort to ensure validity of its findings. The retrospective study identified mCSPC patients who initiated ERLEADA or enzalutamide between December 16, 2018 – December 31, 2023, based on patient data in electronic databases. There were 1,800 ERLEADA and 1,909 enzalutamide initiators who met study criteria.

The analysis demonstrated patients with mCSPC who initiated ERLEADA as their first ARPI had a statistically significant 23 percent reduction in their risk of death at 24 months compared to patients who initiated on enzalutamide (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.62-0.96; P<0.019). The proportion of patients alive at 24 months (87.6 percent) observed in the ERLEADA cohort in this real-world analysis is consistent with that in the Phase 3 TITAN trial (82.4 percent).1 TITAN demonstrated a statistically significant superior overall survival benefit of ERLEADA plus androgen deprivation therapy (ADT) compared to ADT alone at the primary analysis after a median 22.7 months of follow-up (HR 0.67; 95% CI, 0.51-0.89; P=0.005) and at the final analysis after a median 44 months of follow-up (HR 0.65; 95% CI, 0.53-0.79; P<0.0001).1,2

"This real-world evidence showed a statistically significant and clinically meaningful improvement in survival with apalutamide over enzalutamide in patients with mCSPC at 24 months," said Neal Shore, M.D., F.A.C.S., Steering Committee Chair and Medical Director, Carolina Urologic Research Center and study investigator.* "Head-to-head, randomized and controlled Phase 3 studies have been the gold standard for comparing the effectiveness of oncology medicines, however, prospective ARPI comparator trials have not been conducted. This real-world study is provocative as the comprehensive data and rigorous methodology used in this study offers real-world insights on overall survival which can provide prescribers with information to consider when choosing an ARPI."

"ERLEADA is the only ARPI to demonstrate a survival benefit as early as 22 months, as seen in the TITAN study. Since ERLEADA’s approval, multiple ARPIs have been introduced, but no one has directly compared their effectiveness on a large scale – until now," said Luca Dezzani, M.D., U.S. Vice President, Medical Affairs, Solid Tumors, Johnson & Johnson Innovative Medicine. "With a decade-plus legacy in prostate cancer, we have pushed the field further with this additional evidence showing an overall survival benefit with ERLEADA, which is a patient-centric option taken as just one pill, once daily."

Some limitations of this study include potential miscoding or missing information in the data sources; however, the data sources used in this study were deemed fit for purpose to identify the patient population correctly and to assess survival. Lastly, while survival was assessed at 24 months for statistical comparison, longer-term studies are needed to fully evaluate the therapeutic effects of these treatments.

About Prostate Cancer
Approximately 300,000 people are diagnosed with prostate cancer each year in the U.S.3 Up to 40 percent of patients will be classified as high-risk.4 Despite advancements in treatment, disease recurrence remains substantial; up to 50% of patients within ten years of surgery experience recurrence and carry a significant risk of disease progression and death.5 It’s estimated that more than 35,000 men will succumb to their prostate cancer in 2024, which reinforces the importance of choosing the best possible therapy early for patients with advanced prostate cancer.3

About ERLEADA
ERLEADA (apalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC). ERLEADA received U.S. Food and Administration (FDA) approval for nmCRPC in February 2018 and received U.S. FDA approval for mCSPC in September 2019. ERLEADA is the first and only next-generation androgen receptor inhibitor offering a once-daily, single-tablet treatment option for patients. To date, more than 200,000 patients worldwide have been treated with ERLEADA. Additional studies are ongoing in the evaluation of ERLEADA for the treatment of localized high-risk or locally advanced prostate cancer, including the Phase 3 ATLAS (NCT02531516) and PROTEUS (NCT03767244) studies.

For more information, visit www.ERLEADA.com.

ERLEADA IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Cerebrovascular and Ischemic Cardiovascular Events — In a randomized study (SPARTAN) of patients with nmCRPC, ischemic cardiovascular events occurred in 3.7% of patients treated with ERLEADA and 2% of patients treated with placebo. In a randomized study (TITAN) in patients with mCSPC, ischemic cardiovascular events occurred in 4.4% of patients treated with ERLEADA and 1.5% of patients treated with placebo. Across the SPARTAN and TITAN studies, 4 patients (0.3%) treated with ERLEADA and 2 patients (0.2%) treated with placebo died from an ischemic cardiovascular event. Patients with history of unstable angina, myocardial infarction, congestive heart failure, stroke, or transient ischemic attack within 6 months of randomization were excluded from the SPARTAN and TITAN studies.

In the SPARTAN study, cerebrovascular events occurred in 2.5% of patients treated with ERLEADA and 1% of patients treated with placebo. In the TITAN study, cerebrovascular events occurred in 1.9% of patients treated with ERLEADA and 2.1% of patients treated with placebo. Across the SPARTAN and TITAN studies, 3 patients (0.2%) treated with ERLEADA, and 2 patients (0.2%) treated with placebo died from a cerebrovascular event.

Cerebrovascular and ischemic cardiovascular events, including events leading to death, occurred in patients receiving ERLEADA. Monitor for signs and symptoms of ischemic heart disease and cerebrovascular disorders. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Consider discontinuation of ERLEADA for Grade 3 and 4 events.

Fractures — In a randomized study (SPARTAN) of patients with nmCRPC, fractures occurred in 12% of patients treated with ERLEADA and in 7% of patients treated with placebo. In a randomized study (TITAN) of patients with mCSPC, fractures occurred in 9% of patients treated with ERLEADA and in 6% of patients treated with placebo. Evaluate patients for fracture risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents.

Falls — In a randomized study (SPARTAN), falls occurred in 16% of patients treated with ERLEADA compared with 9% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Falls occurred in patients receiving ERLEADA with increased frequency in the elderly. Evaluate patients for fall risk.

Seizure — In two randomized studies (SPARTAN and TITAN), 5 patients (0.4%) treated with ERLEADA and 1 patient treated with placebo (0.1%) experienced a seizure. Permanently discontinue ERLEADA in patients who develop a seizure during treatment. It is unknown whether anti-epileptic medications will prevent seizures with ERLEADA. Advise patients of the risk of developing a seizure while receiving ERLEADA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others.

Severe Cutaneous Adverse Reactions — Fatal and life-threatening cases of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) occurred in patients receiving ERLEADA.

Monitor patients for the development of SCARs. Advise patients of the signs and symptoms of SCARs (eg, a prodrome of fever, flu-like symptoms, mucosal lesions, progressive skin rash, or lymphadenopathy). If a SCAR is suspected, interrupt ERLEADA until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other Grade 4 skin reactions, permanently discontinue ERLEADA [see Dosage and Administration (2.2)].

Interstitial Lung Disease (ILD)/Pneumonitis — Fatal and life-threatening interstitial lung disease (ILD) or pneumonitis can occur in patients treated with ERLEADA.

Post-marketing cases of ILD/pneumonitis, including fatal cases, occurred in patients treated with ERLEADA. Across clinical trials (TITAN and SPARTAN, n=1327), 0.8% of patients treated with ERLEADA experienced ILD/pneumonitis, including 0.2% who experienced Grade 3 events [see Adverse Reactions (6.1, 6.2)].

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold ERLEADA if ILD/pneumonitis is suspected. Permanently discontinue ERLEADA in patients with severe ILD/pneumonitis or if no other potential causes of ILD/pneumonitis are identified [see Dosage and Administration (2.2)].

Embryo-Fetal Toxicity — The safety and efficacy of ERLEADA have not been established in females. Based on findings from animals and its mechanism of action, ERLEADA can cause fetal harm and loss of pregnancy when administered to a pregnant female. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of ERLEADA [see Use in Specific Populations (8.1, 8.3)].

ADVERSE REACTIONS

The most common adverse reactions (≥10%) that occurred more frequently in the ERLEADA-treated patients (≥2% over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.

Laboratory Abnormalities — All Grades (Grade 3-4)

Hematology — In the TITAN study: white blood cell decreased ERLEADA 27% (0.4%), placebo 19% (0.6%). In the SPARTAN study: anemia ERLEADA 70% (0.4%), placebo 64% (0.5%); leukopenia ERLEADA 47% (0.3%), placebo 29% (0%); lymphopenia ERLEADA 41% (1.8%), placebo 21% (1.6%)
Chemistry — In the TITAN study: hypertriglyceridemia ERLEADA 17% (2.5%), placebo 12% (2.3%). In the SPARTAN study: hypercholesterolemia ERLEADA 76% (0.1%), placebo 46% (0%); hyperglycemia ERLEADA 70% (2%), placebo 59% (1.0%); hypertriglyceridemia ERLEADA 67% (1.6%), placebo 49% (0.8%); hyperkalemia ERLEADA 32% (1.9%), placebo 22% (0.5%)
Rash — In 2 randomized studies (SPARTAN and TITAN), rash was most commonly described as macular or maculopapular. Adverse reactions of rash were 26% with ERLEADA vs 8% with placebo. Grade 3 rashes (defined as covering >30% body surface area [BSA]) were reported with ERLEADA treatment (6%) vs placebo (0.5%).

The onset of rash occurred at a median of 83 days. Rash resolved in 78% of patients within a median of 78 days from onset of rash. Rash was commonly managed with oral antihistamines, topical corticosteroids, and 19% of patients received systemic corticosteroids. Dose reduction or dose interruption occurred in 14% and 28% of patients, respectively. Of the patients who had dose interruption, 59% experienced recurrence of rash upon reintroduction of ERLEADA.

Hypothyroidism — In 2 randomized studies (SPARTAN and TITAN), hypothyroidism was reported for 8% of patients treated with ERLEADA and 1.5% of patients treated with placebo based on assessments of thyroid-stimulating hormone (TSH) every 4 months. Elevated TSH occurred in 25% of patients treated with ERLEADA and 7% of patients treated with placebo. The median onset was at the first scheduled assessment. There were no Grade 3 or 4 adverse reactions. Thyroid replacement therapy, when clinically indicated, should be initiated or dose adjusted.

DRUG INTERACTIONS

Effect of Other Drugs on ERLEADA — Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties. No initial dose adjustment is necessary; however, reduce the ERLEADA dose based on tolerability [see Dosage and Administration (2.2)].

Effect of ERLEADA on Other Drugs

CYP3A4, CYP2C9, CYP2C19, and UGT Substrates — ERLEADA is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans. Concomitant use of ERLEADA with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications. Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued. Concomitant administration of ERLEADA with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure. Use caution if substrates of UGT must be co-administered with ERLEADA and evaluate for loss of activity.

P-gp, BCRP, or OATP1B1 Substrates — Apalutamide is a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically. Concomitant use of ERLEADA with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications. Use caution if substrates of P-gp, BCRP, or OATP1B1 must be co-administered with ERLEADA and evaluate for loss of activity if medication is continued.

On October 2, 2024 UroGen Pharma Ltd, a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers, reported that the first patient was dosed in the Phase 3 clinical trial of investigational drug UGN-103 (mitomycin) for intravesical solution in development for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) (Press release, UroGen Pharma, OCT 2, 2024, View Source [SID1234647005]). UGN-103 is a next-generation novel mitomycin-based formulation.

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"Reaching this Phase 3 trial milestone for UGN-103 highlights our drive to innovate and bring forward cutting-edge treatments for low-grade intermediate-risk non-muscle invasive bladder cancer," said Liz Barrett, President and Chief Executive Officer, UroGen. "UGN-103 represents a significant step forward, offering potential improvements in manufacturing, convenience, and cost. We are excited about the potential of this next-generation formulation and look forward to furthering its development to advance the care of patients."

The UGN-103 formulation uses UroGen’s RTGel platform technology, a proprietary sustained-release, reverse-thermal hydrogel with the potential to improve the therapeutic profiles of existing drugs. The U.S. Food and Drug Administration (FDA) accepted the Investigational New Drug Application for UGN-103 in April 2024, permitting the drug’s investigational use in adults with LG-IR-NMIBC, a highly recurrent disease. UGN-103 is planned to follow the potential FDA approval and launch of UGN-102 (mitomycin) for intravesical solution for LG-IR-NMIBC. UroGen completed the New Drug Application (NDA) submission for UGN-102 ahead of schedule with potential FDA approval in early 2025, if the NDA is accepted for filing by the FDA and priority review is granted.

The UTOPIA study is a single-arm, multicenter study that will evaluate the efficacy and safety of UGN-103. UroGen is aiming to enroll 87 patients with LG-IR-NMIBC in the UTOPIA study. Patients will receive 75 mg of UGN-103 via intravesical instillation once a week for 6 weeks. Efficacy will be assessed by the complete response rate at the three-month visit. Patients who have a complete response at the three-month visit, defined as having no detectable disease in the bladder, will enter the follow-up period of the study. During the follow-up period, patients will return to the clinic every three months for evaluation of response. Patients will remain on study until disease recurrence, disease progression, death, or the last patient completes 12 months of follow-up (i.e., 15 months after the first instillation), whichever occurs first. To learn more about the UTOPIA trial, visit clinicaltrials.gov/NCT06331299.

About UGN-103

UGN-103 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin being developed for the treatment of LG-IR-NMIBC. Anticipated advantages of UGN-103 include a new formulation of mitomycin that may considerably shorten the manufacturing process and simplify the reconstitution procedure. UroGen announced on September 16, 2024, that it received from the United States Patent and Trademark Office (USPTO), a Notice of Allowance covering, among other things, the use of UGN-103 in the treatment of LG-IR-NMIBC. The U.S. patent, once issued, will have an expiration date in December 2041. UGN-103 will utilize UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen completed the NDA submission for UGN-102 in August 2024, ahead of schedule, with a potential FDA decision as early as the first quarter of 2025, if the NDA is accepted for filing by the FDA and priority review is granted.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

In the U.S. bladder cancer is the second most common urologic cancer in men. LG-IR-NMIBC represents approximately 22,000 newly diagnosed bladder cancer patients each year and an estimated 60,000 recurrences annually among patients diagnosed from previous years. Bladder cancer primarily affects older populations with the median age of diagnosis 73 years and an increased risk of comorbidities. Guideline recommendations for the management of NMIBC include TURBT as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.

On October 2, 2024 Volastra Therapeutics, a clinical-stage biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to VLS-1488, the company’s internally discovered KIF18A inhibitor (Press release, Volastra Therapeutics, OCT 2, 2024, View Source [SID1234647004]). The designation has been granted for the treatment of patients with platinum-resistant high-grade serous ovarian cancer (HGSOC).

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"Platinum-resistant high-grade serous ovarian cancer is marked by poor prognosis, highlighting the urgent need for new therapies for this devastating disease," said Scott Drutman, M.D., Ph.D., Head of Research & Development and Chief Medical Officer. "Fast Track designation for VLS-1488 reaffirms the clear potential of KIF18A inhibition to address this unmet medical need and represents a critical step towards bringing these novel therapeutics to patients. We look forward to working closely with the FDA as we advance the development of inhibitors against this promising target."

Fast Track designation is a program intended to facilitate and expedite the development and review of new drugs for the treatment of a serious or life-threatening condition. To qualify for this designation, there must be clear data demonstrating the drug has potential to address unmet medical need in the designated condition.

In the U.S. alone, there are more than 20,000 new cases of ovarian cancer each year, over 75% of which are advanced. Most of these patients will see disease progression on platinum-based chemotherapy. Sovilnesib, the second of Volastra’s two KIF18A inhibitors, which was in-licensed from Amgen in 2023, has previously been granted Fast Track designation in this indication. Each of Volastra’s two KIF18A inhibitors, VLS-1488 and sovilnesib, has unique profiles and are both enrolling patients in early-phase studies.

The Phase I/II trial for VLS-1488 is evaluating safety, tolerability and preliminary efficacy in patients with advanced tumors, including HGSOC. Further details of the trial can be found at www.clinicaltrials.gov under NCT identifier: NCT05902988.