May 05, 2024
Erleads plus androgen deprivation therapy showed a 100% BCR-free rate at the 24-month mark in patients with high-risk localized prostate cancer
New findings from a Phase 2 study showcase the efficacy of ERLEADA (apalutamide) alongside androgen deprivation therapy (ADT) as adjuvant treatment post-radical prostatectomy (RP) in patients with high-risk localized prostate cancer (HRLPC). These results, presented by Janssen, indicate a remarkable 100% biochemical recurrence (BCR)-free rate at the 24-month mark following RP.
The study, known as Apa-RP, was conducted as an open-label, single-arm endeavor. It aimed to assess the outcomes of combining ERLEADA with ADT in patients who had undergone RP. The pivotal observation was the absence of confirmed biochemical recurrence after an additional 12 months of follow-up among patients receiving 12 months of ERLEADA plus ADT adjuvant to RP, effectively fulfilling the primary endpoint.
Key data from the study underscored a notable serum testosterone recovery rate (≥150 ng/dL) of 76.4% at the 12-month mark, with a confidence interval of 95%. The safety profile of ERLEADA in conjunction with ADT remained consistent with previous reports, with treatment-emergent adverse events (TEAEs) documented in 99.1% of patients, of which 22.2% were graded as 3-4 severity.
This Phase 2 endeavor, executed across multiple centers and in an open-label, single-arm fashion, enrolled a cohort of 108 patients sourced from 32 community urologic practices in the United States. The patient pool consisted of individuals who were treatment-naïve with HRLPC, had undergone RP, and were subsequently treated with ERLEADA at a dosage of 240 mg once daily for 12 cycles (where 1 cycle equated to 28 days), along with ADT for 12 months.
The primary endpoint of the study revolved around the BCR-free rate, defined as the absence of two consecutive prostate-specific antigen (PSA) levels surpassing 0.2 ng/mL. Secondary endpoints included the assessment of the testosterone recovery rate and an evaluation of safety parameters.
May 05, 2024
TAR-210 showed significant recurrence-free survival and complete response in patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer
The latest findings regarding TAR-210 reveal a promising 90% recurrence-free survival and 90% complete response in patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC), respectively.
Janssen recently provided updates on the outcomes of TAR-210, a targeted releasing system administered intravesically to ensure sustained, localized release of erdafitinib into the bladder. This pertains to a Phase 1 study, encompassing various cohorts and focusing on the safety and effectiveness of TAR-210 in NMIBC patients harboring specific FGFR alterations.
As of the data cutoff in March 22, 2024, a total of 64 patients received TAR-210 treatment across two cohorts. In Cohort 1, comprising patients with high-risk NMIBC unresponsive to Bacillus Calmette-Guérin (BCG) treatment, the 12-month recurrence-free survival rate stood at 90%. Meanwhile, in Cohort 3, featuring individuals with intermediate-risk NMIBC, 31 patients were assessable for efficacy, revealing a commendable complete response rate of 90%.
Regarding adverse events, the most prevalent were graded as 1 or 2 lower urinary tract issues. Notably, there were no instances of dose-limiting toxicities or fatalities. Discontinuation due to treatment-emergent adverse events occurred in only 3% of patients, with reports mainly revolving around low-grade urinary symptoms. Additionally, two patients experienced serious adverse events, namely pyelonephritis and sepsis, and urinary tract infection (UTI) and sepsis.
TAR-210 stands as an investigational system, meticulously designed to deliver erdafitinib locally and sustainably within the bladder. Erdafitinib, in its oral form, has garnered FDA approval under the brand name BALVERSA® for treating locally advanced or metastatic urothelial carcinoma with specific FGFR3 genetic alterations, following progression post-prior systemic therapy. However, BALVERSA is not recommended for patients eligible for, but not yet treated with, PD-1 or PD-L1 inhibitors.
Bladder cancer ranks as the sixth most common cancer in the United States, with a yearly influx of over 83,000 diagnoses. A significant portion of these cases, approximately 75-85%, falls under the category of NMIBC. Presently, standard treatment entails adjuvant intravesical immunotherapy with BCG or intravesical chemotherapy for patients with intermediate- to high-risk NMIBC. Nevertheless, a notable proportion, ranging from 30 to 40%, does not respond to BCG, consequently confronting the risk of disease recurrence or progression. In instances of high-risk NMIBC, where BCG therapy proves ineffective, radical cystectomy emerges as the primary recourse, necessitating the removal of the bladder, followed by the creation of urinary diversion mechanisms.
TAR-210 continues to undergo evaluation as an investigational intravesical targeted releasing system for erdafitinib. Its safety and efficacy are currently under scrutiny in a Phase 1 study (NCT05316155) encompassing patients with both muscle-invasive bladder cancer (MIBC) and NMIBC. The study partitions patients into four distinct cohorts, each reflecting different disease presentations. Cohort 1 deals with patients experiencing recurrent, BCG-unresponsive high-risk NMIBC, who either reject or are unfit for radical cystectomy. Cohort 2 comprises similar patients but scheduled for radical cystectomy. Cohort 3 encompasses those with recurrent, intermediate-risk NMIBC harboring a history of low-grade papillary disease. Notably, visible tumors are prerequisites for inclusion in Cohort 3. Finally, Cohort 4 comprises patients with MIBC. The primary endpoint of this investigation revolves around safety, with adverse events and dose-limiting toxicity as focal points. Secondary endpoints encompass pharmacokinetics, recurrence-free survival rates, complete response rates, and duration of complete response across various cohorts.
Data from Phase 2b SunRISe-1 exploration demonstrates remarkable outcomes of TAR-200 monotherapy, achieving over 80% complete remission in patients grappling with high-risk non–muscle-invasive bladder cancer (HR-NMIBC)
The latest outcomes reveal swift attainment of complete remission (CR), with 98% achieving CR within mere 12 weeks of initiating TAR-200 treatment. TAR-200 exhibits enduring CR outcomes in patients with Bacillus Calmette-Guérin (BCG)–unresponsive HR-NMIBC featuring carcinoma in situ, a realm plagued by scarce treatment avenues for patients.
Janssen presented updated findings from Cohort 2 of Phase 2b SunRISe-1 endeavor, delving into the efficacy and safety of TAR-200 monotherapy among individuals with BCG-unresponsive HR-NMIBC featuring carcinoma in situ, who either cannot undergo or opt against radical cystectomy.
The evaluation comprised 85 patients who underwent TAR-200 monotherapy. A centrally confirmed CR rate of 82.8% was observed via urine cytology and/or biopsy. By the U.S. Food and Drug Administration (FDA) directives, the study protocol precluded retreatment for nonresponders. The estimated one-year duration of response (DOR) rate stands at 74.6%, with responders being monitored for a median of 29.9 weeks; 85% of responders (41 out of 48) remained in CR as of January 2, 2024, with no instances of progression to muscle-invasive bladder cancer or metastasis among responders. Nearly all CRs (98%, 47 out of 48) were attained during the initial disease assessment at week 12, with four out of five patients who completed two years of treatment maintaining CR status. The investigator-assessed confirmed CR rate exhibited a strong correlation with central findings.
Treatment-related adverse events (TRAEs) were documented in 61 patients (71.8%). The most prevalent (≥10%) included pollakiuria (35.3%), dysuria (29.4%), micturition urgency (15.3%), and urinary tract infections (15.3%). Grade 3 or higher TRAEs occurred in seven patients (8.2%), with four patients (4.7%) encountering one or more serious TRAEs. TRAEs prompted discontinuation in four patients (4.7%), with no fatalities reported.
TAR-200, an investigative targeted release system engineered to deliver a prolonged local release of gemcitabine into the bladder, is administered in a physician’s office within a brief 3- to 5-minute procedure devoid of anesthesia. In December 2023, TAR-200 garnered Breakthrough Therapy Designation (BTD) from the FDA for its potential application in treating patients with BCG-unresponsive HR-NMIBC, who either cannot undergo or choose to forgo radical cystectomy.
Bladder cancer ranks as the sixth most prevalent cancer in the United States, with over 83,000 new diagnoses annually, with NMIBC constituting approximately 75-85% of all newly diagnosed cases. Though BCG immunotherapy has been the stalwart treatment for nearly five decades, 30-40% of patients do not respond to BCG and confront disease recurrence or progression. In such scenarios, radical cystectomy emerges as the primary recourse, necessitating the creation of urinary diversion for waste management.
SunRISe-1 (NCT04640623) is a randomized, parallel-assignment, open-label Phase 2 clinical inquiry exploring the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC patients with carcinoma in situ who either cannot undergo or opt against radical cystectomy. Participants are randomly assigned to one of four cohorts: TAR-200 with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), cetrelimab alone (Cohort 3), or TAR-200 alone for patients with papillary disease only (Cohort 4). The primary endpoint is the CR rate at any point in time. Secondary endpoints include DOR, overall survival, pharmacokinetics, quality of life, safety, and tolerability. Cohorts 1 and 3 ceased further enrollment as of June 1, 2023.