Updated results reinforce the potential of TAR-210 to
transform treatment of non–muscle-invasive bladder cancer
with fibroblast growth factor receptor (FGFR)
alterations
SAN
ANTONIO, May 5, 2024 /PRNewswire/ -- Johnson &
Johnson announced today updated results from an open-label,
multicenter, multi-cohort Phase 1 study of the safety and efficacy
of TAR-210, an intravesical targeted releasing system designed to
provide sustained, local release of erdafitinib into the bladder,
in patients with non–muscle-invasive bladder cancer (NMIBC) with
select FGFR alterations. These data were featured today in
an Oral Presentation Session (Abstract # PD48-02) at the 2024
American Urological Association (AUA) Annual Meeting taking place
May 3-6, 2024, in San Antonio, Texas.
Results featured updated data from Cohort 1 (C1), patients with
recurrent, Bacillus Calmette-Guérin (BCG)–unresponsive high-risk
(HR) NMIBC (high-grade Ta/T1; papillary only) who refused or were
ineligible for radical cystectomy and Cohort 3 (C3), patients with
recurrent, intermediate-risk NMIBC (Ta/T1) low-grade papillary
disease left in situ as tumor marker lesions. First results were
featured at the European Society for Medical Oncology 2023
Congress, with interim results presented at the European
Association of Urology (EAU) 2024 Annual Congress.
"Advancement in the treatment landscape of high- or
intermediate-risk non–muscle-invasive bladder cancer has remained
stagnant for more than 50 years," said Antoni Vilaseca,* M.D., Ph.D., of the Hospital
Clínic de Barcelona, presenting
author of the Phase 1 TAR-210 study. "Results presented today
further underscore that TAR-210 for the localized treatment of
bladder cancer may offer a promising alternative for patients with
limited treatment options."
At the data cutoff of March 22,
2024, 64 patients had been treated with TAR-210 across the 2
cohorts. Of the 21 patients in C1 with HR-NMIBC, the 12-month
recurrence-free (RF) survival rate was 90%. In C3, 31 patients were
efficacy evaluable with a complete response (CR) rate of
90%.1
The most common treatment emergent adverse events (TEAEs) were
Grade 1/2 lower urinary tract events. There were no dose-limiting
toxicities and no deaths. Two patients (3%) discontinued the study
due to TEAEs of low-grade urinary symptoms and two patients had
serious TEAEs with pyelonephritis and sepsis or UTI and sepsis,
respectively.1
"FGFR genetic alterations are most common in NMIBC," said
Sabine Brookman-May, M.D., Vice
President, Late Development Oncology, Johnson & Johnson
Innovative Medicine. "These results further support the potential
of TAR-210 with quarterly administration as a bladder-sparing and
BCG-free treatment option, underscoring our deep commitment to
pioneering novel therapies for patients who face limited treatment
avenues."
TAR-210 is an investigational targeted releasing system designed
to provide sustained local release of erdafitinib. Oral erdafitinib
was approved by the U.S. Food and Drug Administration (FDA) as
BALVERSA® (erdafitinib) for patients with locally
advanced or metastatic urothelial carcinoma (mUC) with susceptible
FGFR3 genetic alterations that have progressed on or after
at least one line of prior systemic therapy. BALVERSA®
is not recommended for the treatment of patients who are eligible
for and have not received prior PD-1 or PD-L1 inhibitor
therapy.2
Bladder cancer ranks as the sixth most prevalent cancer in the
U.S., with over 83,000 individuals receiving diagnoses
annually.3 NMIBC constitutes approximately 75-85% of
these cases.4 Currently, adjuvant intravesical
immunotherapy with BCG or intravesical chemotherapy is the standard
of care for patients with intermediate- and high-risk
NMIBC.5 Between 30 and 40% of patients do not respond to
BCG, facing disease recurrence or progression.6 In such
scenarios of HR-NMIBC, radical cystectomy (removal of the bladder)
emerges as the primary treatment option. This major abdominal
procedure requires a urinary diversion to be created to collect and
store urine.7
About TAR-210
TAR-210 is an investigational
erdafitinib intravesical targeted releasing system. The safety and
efficacy of TAR-210 is being evaluated in a Phase 1 study
(NCT05316155) in patients with muscle-invasive bladder cancer
(MIBC) and NMIBC. The study categorizes patients into 4 cohorts
based on their disease presentation. Cohort 1 includes patients
with recurrent, BCG-unresponsive high-risk NMIBC with concomitant
high-grade papillary disease who have refused or are ineligible for
radical cystectomy (RC). Cohort 2 includes patients with the same
presentation, but who are scheduled for RC. Cohort 3 includes
patients with recurrent, intermediate-risk NMIBC with a history of
low-grade papillary disease. To be eligible for C3, the presence of
visible tumor(s) is required. Cohort 4 includes patients with MIBC.
The primary endpoint of the study is safety (adverse events,
including dose-limiting toxicity). Secondary endpoints include
pharmacokinetics, RF survival in patients in C1 and C2, CR rate and
duration of CR in patients in C3 and pathologic CR rate in
C4.8
About BALVERSA®
BALVERSA® (erdafitinib) is a once-daily, oral
FGFR kinase inhibitor indicated for the treatment of adult
patients with locally advanced or mUC with susceptible fibroblast
growth factor receptor 3 (FGFR3) genetic alterations whose
disease has progressed on or after at least one line of prior
systemic therapy. BALVERSA ® is not recommended for
the treatment of patients who are eligible for and have not
received prior PD-1 or PD-(L)1 inhibitor
therapy.2 Patients are selected for therapy based
on an FDA-approved companion diagnostic for BALVERSA®.
Information on FDA-approved tests for the detection of FGFR
genetic alterations in urothelial cancer is available at:
http://www.fda.gov/CompanionDiagnostics.
BALVERSA® received Breakthrough Therapy Designation
from the U.S. FDA in 2018 and received accelerated approval in
2019 for the treatment of adults with locally advanced or mUC that
has susceptible FGFR3 or fibroblast growth factor receptor 2
(FGFR2) genetic alterations and who have progressed during
or following at least one line of prior platinum-containing
chemotherapy, including within 12 months of neoadjuvant or adjuvant
platinum-containing chemotherapy.2
The Company submitted a marketing authorization application to
the European Medicines Agency in September
2023 for BALVERSA ® as a treatment for
adult patients with FGFR3-altered, locally advanced
unresectable or mUC that has progressed following therapy with a
PD-(L)1 inhibitor.
In 2008, Janssen Pharmaceuticals entered into an exclusive
worldwide license and collaboration agreement with Astex
Pharmaceuticals to develop and commercialize
BALVERSA®.
For more information, visit www.BALVERSA.com.
BALVERSA® IMPORTANT SAFETY
INFORMATION
WARNING AND PRECAUTIONS
The safety population described in the Warnings and Precautions
reflect a pooled safety population of 479 patients with advanced
urothelial cancer and FGFR alterations who received
BALVERSA®.
Ocular Disorders – BALVERSA® can cause ocular
disorders, including central serous retinopathy/retinal pigment
epithelial detachment (CSR/RPED) resulting in visual field defect.
CSR/RPED occurred in 22% of patients treated with
BALVERSA®, with a median time to first onset of 46 days.
In 104 patients with CSR, 40% required dose interruptions and 56%
required dose reductions; 2.9% of BALVERSA®-treated
patients required permanent discontinuation for CSR. Of the 24
patients who restarted BALVERSA® after dose interruption
with or without dose reduction, 67% had recurrence and/or worsening
of CSR after restarting. CSR was ongoing in 41% of the 104 patients
at the time of last evaluation.
Dry eye symptoms occurred in 26% of BALVERSA®-treated
patients. All patients should receive dry eye prophylaxis with
ocular demulcents as needed.
Perform monthly ophthalmological examinations during the first 4
months of treatment and every 3 months afterwards, and urgently at
any time for visual symptoms. Ophthalmological examination should
include assessment of visual acuity, slit lamp examination,
fundoscopy, and optical coherence tomography. Withhold or
permanently discontinue BALVERSA® based on severity
and/or ophthalmology exam findings.
Hyperphosphatemia and Soft Tissue Mineralization –
BALVERSA® can cause hyperphosphatemia leading to soft
tissue mineralization, cutaneous calcinosis, non-uremic
calciphylaxis and vascular calcification. Increases in phosphate
levels are a pharmacodynamic effect of BALVERSA® [see
Pharmacodynamics (12.2)]. Increased phosphate occurred in
73% of BALVERSA®-treated patients. The median onset time
of increased phosphate was 16 days (range: 8–421) after initiating
BALVERSA®. Twenty-four percent of patients received
phosphate binders during treatment with BALVERSA®.
Vascular calcification was observed in 0.2% of patients treated
with BALVERSA®.
Monitor for hyperphosphatemia throughout treatment. In all
patients, restrict phosphate intake to 600-800 mg daily and avoid
concomitant use of agents that may increase serum phosphate levels.
If serum phosphate is above 7.0 mg/dL, consider adding an oral
phosphate binder until serum phosphate level returns to <7.0
mg/dL. Withhold, dose reduce, or permanently discontinue
BALVERSA® based on duration and severity of
hyperphosphatemia.
Embryo-Fetal Toxicity – Based on the mechanism of
action and findings in animal reproduction studies,
BALVERSA® can cause fetal harm when administered to a
pregnant female. In a rat embryo-fetal toxicity study, erdafitinib
caused malformations and embryo-fetal death at maternal exposures
that were less than the human exposures at the maximum human
recommended dose based on AUC. Advise pregnant patients of the
potential risk to the fetus. Advise female patients of reproductive
potential to use effective contraception during treatment with
BALVERSA® and for one month after the last dose. Advise
male patients with female partners of reproductive potential to use
effective contraception during treatment with BALVERSA®
and for one month after the last dose.
Adverse Reactions
In this pooled safety population described in Warnings and
Precautions, the median duration of treatment was 4.8 months
(range: 0.1 to 43 months). The most common (>20%) adverse
reactions, including laboratory abnormalities, were increased
phosphate, nail disorders, stomatitis, diarrhea, increased
creatinine, increased alkaline phosphatase, increased alanine
aminotransferase, decreased hemoglobin, decreased sodium, increased
aspartate aminotransferase, fatigue, dry mouth, dry skin, decreased
phosphate, decreased appetite, dysgeusia, constipation, increased
calcium, dry eye, palmar-plantar erythrodysesthesia syndrome,
increased potassium, alopecia, and central serous
retinopathy.
In Cohort 1 of the BLC3001 (NCT03390504, THOR) study:
- Serious adverse reactions occurred in 41% of patients who
received BALVERSA®. Serious reactions in >2% of
patients included urinary tract infection (4.4%), hematuria (3.7%),
hyponatremia (2.2%), and acute kidney injury (2.2%). Fatal adverse
reactions occurred in 4.4% of patients who received
BALVERSA®, including sudden death (1.5%), pneumonia
(1.5%), renal failure (0.7%), and cardiorespiratory arrest
(0.7%).
- Permanent discontinuation of BALVERSA® due to
an adverse reaction occurred in 14% of patients. Adverse reactions
which resulted in permanent discontinuation of BALVERSA®
in >2% of patients included nail disorders (3%) and eye
disorders (2.2%).
- Dosage interruptions of BALVERSA® due to an
adverse reaction occurred in 72% of patients. Adverse reactions
which required dosage interruption in >4% of patients included
nail disorders (22%), stomatitis (19%), eye disorders (16%),
palmar-plantar erythrodysesthesia syndrome (15%), diarrhea (10%),
hyperphosphatemia (7%), increased aspartate aminotransferase (6%),
and increased alanine aminotransferase (5%).
- Dose reductions of BALVERSA® due to an adverse
reaction occurred in 69% of patients. Adverse reactions which
required dose reductions in >4% of patients included nail
disorders (27%), stomatitis (19%), eye disorders (17%),
palmar-plantar erythrodysesthesia syndrome (12%), diarrhea (7%),
dry mouth (4.4%), and hyperphosphatemia (4.4%).
- Clinically relevant adverse reactions in <15% of patients
who received BALVERSA® included nausea (15%),
pyrexia (15%), epistaxis (13%), vomiting (10%), and arthralgia
(10%).
Drug Interactions
Effects of Other Drugs on BALVERSA®
- Moderate CYP2C9 or Strong CYP3A4 Inhibitors: Consider
alternative agents; however, if co-administration is unavoidable,
monitor closely for adverse reactions.
- Strong CYP3A4 inducers: Avoid co-administration
with BALVERSA®.
- Moderate CYP3A4 inducers: If co-administration is required at
the start of BALVERSA® treatment, administer
BALVERSA® at a dose of 9 mg daily.
- Serum phosphate level-altering agents: Avoid co-administration
with agents that can alter serum phosphate levels before the
initial dose increase period based on serum phosphate levels.
Effect of BALVERSA® on Other Drugs
- P-gp substrates: If co-administration is unavoidable, separate
BALVERSA® administration by at least 6 hours before or
after administration of P-gp substrates with narrow therapeutic
indices.
Please click here to see full
BALVERSA® Prescribing Information.
About High-Risk Non–Muscle-Invasive Bladder
Cancer
High-risk non-muscle-invasive bladder cancer
(HR-NMIBC) is a type of non-invasive bladder cancer that is more
likely to recur or spread beyond the lining of the bladder, called
the urothelium, and progress to invasive bladder cancer compared to
low-risk NMIBC. HR-NMIBC makes up 15-44% of patients with NMIBC and
is characterized by a combination of high-grade, large tumor size,
presence of multiple tumors, and carcinoma in situ. Radical
cystectomy (RC) is currently recommended for NMIBC patients who
fail BCG therapy, with over 90% cancer-specific survival if
performed before muscle-invasive progression. Given that NMIBC
typically affects older patients, many may be unwilling or unfit to
undergo RC. The high rates of recurrence and progression can pose
significant morbidity and distress for these
patients.9
About Johnson & Johnson
At Johnson &
Johnson, we believe health is everything. Our strength in
healthcare innovation empowers us to build a world where complex
diseases are prevented, treated, and cured, where treatments are
smarter and less invasive, and solutions are personal. Through our
expertise in Innovative Medicine and MedTech, we are uniquely
positioned to innovate across the full spectrum of healthcare
solutions today to deliver the breakthroughs of tomorrow, and
profoundly impact health for humanity. Learn more at
https://www.jnj.com/ or at
www.janssen.com/johnson-johnson-innovative-medicine. Follow us
at @JanssenUS and @JNJInnovMed. Janssen Research
& Development, LLC, and Janssen Biotech, Inc., are both Johnson
& Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding product development and the potential benefits and
treatment impact of TAR-210 or BALVERSA® (erdafitinib).
The reader is cautioned not to rely on these forward-looking
statements. These statements are based on current expectations of
future events. If underlying assumptions prove inaccurate or known
or unknown risks or uncertainties materialize, actual results could
vary materially from the expectations and projections of Janssen
Research & Development, LLC, Janssen Biotech, Inc.,
and/or Johnson & Johnson. Risks and uncertainties include, but
are not limited to: challenges and uncertainties inherent in
product research and development, including the uncertainty of
clinical success and of obtaining regulatory approvals; uncertainty
of commercial success; competition, including technological
advances, new products and patents attained by competitors;
challenges to patents; changes in behavior and spending patterns of
purchasers of health care products and services; changes to
applicable laws and regulations, including global health care
reforms; and trends toward health care cost containment. A further
list and descriptions of these risks, uncertainties and other
factors can be found in Johnson & Johnson's Annual Report on
Form 10-K for the fiscal year ended December
31, 2023, including in the sections captioned "Cautionary
Note Regarding Forward-Looking Statements" and "Item 1A. Risk
Factors," and in Johnson & Johnson's subsequent Quarterly
Reports on Form 10-Q and other filings with the Securities and
Exchange Commission. Copies of these filings are available online
at www.sec.gov, www.jnj.com or on
request from Johnson & Johnson. None of Janssen Research &
Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson
undertakes to update any forward-looking statement as a result of
new information or future events or developments.
*Dr. Vilaseca has not been paid for any media work.
1 Vilaseca A, Jayram G, Raventos C, Shore
ND, Zainfeld D, Kang TW, et al. PD48-02 first safety and efficacy
results of the TAR-210 erdafitinib intravesical delivery system in
patients with non–muscle-invasive bladder cancer with select
FGFR alterations. Journal of Urology.
2024;211.
2 BALVERSA®
[Prescribing Information]. Horsham, PA: Janssen Biotech,
Inc.
3 American Cancer Society.
Cancer facts & figures 2024. Atlanta: American Cancer Society;
2024.
4 Deng S, Meng F, Wang L, et
al. Global research trends in non–muscle invasive bladder cancer:
Bibliometric and visualized analysis. Front Oncol.
2022;12:1044830. Published 2022 Nov 17.
Doi:10.3389/fonc.2022.1044830
5 Laukhtina
E, Abufaraj M, Al-Ani A, et al; European Association of
Urology-Young Academic Urologists (EAU-YAU): Urothelial carcinoma
working group. Intravesical therapy in patients with
intermediate-risk non–muscle-invasive bladder cancer: A systematic
review and network meta-analysis of disease recurrence. Eur Urol
Focus. 2022;8(2):447-456. doi: 10.1016/j.euf.2021.03.016. Epub
2021 Mar 21. PMID:
33762203
6 Zlotta AR, Fleshner NE,
Jewett MA. The management of BCG failure in non–muscle-invasive
bladder cancer: an update. Can Urol Assoc J.
2013;3(6-S4):199.
7 Bladder removal
surgery: What is a radical cystectomy? Bladder Cancer Advocacy
Network. Accessed April 1,
2024.
https://bcan.org/bladder-removal-surgery/.
8
Vilaseca A, Guerrero F, Zainfeld D, Shore ND, Rodriguez Faba
O, Meijer RP, et al. Safety and efficacy of the
erdafitinib (erda) intravesical delivery system, TAR-210, in
patients (pts) with non–muscle-invasive bladder cancer (NMIBC) or
muscle-invasive bladder cancer (MIBC) harboring select FGFR
mutations or fusions: Phase 1 first-in-human study. Journal of
Clinical Oncology.
2023;41.
9 Brooks NA,
O'Donnell MA. Treatment options in non–muscle-invasive bladder
cancer after BCG failure. Indian J Urol. 2015;31(4):312-319.
Accessed March 20, 2024.
doi:10.4103/0970-1591.166475
Media contacts:
Suzanne Frost
+1 416 317-0304
Ania
DiAntonio
+1 215
620-0717
|
Investor contact: Raychel Kruper
investor-relations@its.jnj.com
U.S. Medical Inquiries
+1 800
526-7736
|
View original
content:https://www.prnewswire.com/news-releases/tar-210-results-show-90-recurrence-free-survival-and-90-complete-response-in-patients-with-high-risk-and-intermediate-risk-nonmuscle-invasive-bladder-cancer-respectively-302135657.html
SOURCE Johnson & Johnson