Erdafitinib Intravesical Delivery System Under Exploration in Select FGFR+ NMIBC or MIBC

Exploring new methods of delivery for erdafitinib (Balversa), such as the intravesical drug delivery system TAR-210, may enhance the activity of the agent and minimize systemic toxicities in select patients with non–muscle invasive bladder cancer (NMIBC) or MIBC, according to Antoni Vilaseca, MD, PhD.

Oral delivery of erdafitinib was recently investigated in the multicohort phase 2 THOR-2 trial (NCT04172675) trial. Data from cohorts 2 and 3 of the phase 2 THOR-2 trial (NCT04172675) were concurrently presented at the 2023 Genitourinary Cancers Symposium and demonstrated that the agent had antitumor activity and a favorable toxicity profile in patients with intermediate- or high-risk recurrent NMIBC with FGFR3/2 alterations.^2,3

Now, a first-in-human, phase 1 study (NCT05316155) has been launched to evaluate the safety, efficacy, and pharmacokinetics of TAR-210, a device that is designed to provide localized continuous release of erdafitinib into the bladder of patients with recurrent NMIBC or MIBC harboring select FGFR mutations or fusions.¹

The trial will enroll 4 cohorts of patients. Cohorts 1 and 2 will enroll patients with high-risk, papillary-only NMIBC. Prior to dosing on the trial, these patients will undergo transurethral resection of bladder tumor (TURBT) and have complete resection of all visible disease. Cohort 3 will comprise patients with intermediate-risk NMIBC; these patients must have a visible target lesion before receiving study treatment. Cohort 4 will enroll patients with MIBC; these patients must have TURBT and a remaining tumor size of up to 3 cm before dosing.

“For the first time, we’re analyzing directed therapy in NMIBC [that is] administered intravesically,” said Vilaseca, lead study author and adjunct physician in the Urology Service at the Hospital Clínic de Barcelona, Barcelona, Spain. “If [the approach] is confirmed with low systemic adverse effects [AEs], it [could be] a huge step toward personalized medicine in [those] bearing [these] mutations.”

In an interview with OncLive^®, Vilaseca, who is also an associate medical professor at the Universitat de Barcelona, explained the unique mechanism of the TAR-210 delivery system, expands on the key objectives, trial design, and patient characteristics in the phase 1 trial, and discusses how TAR-210 could address the need for improved delivery of erdafitinib in this patient population, and the future.

OncLive^®: What was the rationale for investigating this novel delivery method? How might it address an unmet need?

Vilaseca: We presented a phase 1, first-in-human study on the use of [the] directed, anti-FGFR [agent] erdafitinib administered into the bladder through a device called TAR-210. This is not the only study [evaluating] the target device. The device is inserted into the bladder and delivers the drug continuously [over] a long period of time. In NMIBC, we are used to administering [intravesical] Bacillus Calmette-Guerin [BCG], mitomycin C, and other drugs. We administer them weekly during a period of 6 to 8 weeks, but after 20 to 30 minutes, the patient [has] already released the drug. For the first time, this device is continuously giving the drug until it has to be [replaced, which is at about] 3 months.

All the preliminary studies [of TAR-210 indicated] that it could be a good administration device. The only drawback that we may have foreseen before starting, and that we’re analyzing during the study, is the AEs that [come with] having a strange [device] inside the bladder.

Could you expand on the trial design and the key objectives?

The objective of this study is to look at the safety and tolerability of both the new device and erdafitinib. We must analyze these components continuously during the study period. As a first-in-human study, we have a dose-escalation period to find the toxicity [of] different doses. We have foreseen that they can be toxic. Then, we will [go on to conduct] the second phase of the study.

Do you foresee any challenges with enrollment to this trial?

Enrollment [may not] be easy. We’re talking about a drug that targets a very specific mutation, [one that is] not seen in all patients NMIBC. We expect 60% to 70% of [the population to have] NMIBC, and 30% [to have] MIBC. Patients must have [the FGFR] mutation [to enroll.]

Since the standard of care [SOC] in high-risk NMIBC is cystectomy, we will only be including patients not suitable for cystectomy in this cohort. In the cohort with MIBC, the SOC is adjuvant chemotherapy. Again, we will only be able to include those [who are] not suitable for this SOC treatment.

If data with the TAR-210 delivery system prove to be positive down the line, how could this device impact the treatment paradigm?

This is a phase 1 study, so we’re [mainly] looking at tolerability. If further studies [of TAR-210] are positive, and we find that intravesical delivery is useful for these different patient cohorts, we will have several benefits. The most important one would be [for] cohort 3, [which includes patients] with intermediate-risk cancer and a history of low-grade tumors with recurrence. [By] treating [these patients] with this device, we’re doing less surgeries [or] chemoresection with mitomycin C.

The other [advantage of TAR-210] is [for] those patients not suitable for neoadjuvant chemotherapy [who] have small tumors. The rationale for neoadjuvant chemotherapy is [its] systemic effect. This device with erdafitinib will not have a systemic effect. [However], for select tumors [that are] small or completely resected, we [may] be able to increase the results of the cystectomy with no systemic AEs if there’s local action with the treatment. The AEs we [anticipate] finding will mainly be local, [in response] to having a device inside the bladder.

Editor’s Note: Dr. Vilaseca did not have any relationships to disclose.

References

1. Vilaseca A, Guerrero F, Zainfield D, 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.J Clin Oncol. 2023;41(suppl 6):TPS583. doi:10.1200/JCO.2023.41.6_suppl.TPS583
2. Daneshmand S, Zaucha R, Gartrell BA, et al. Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 3 interim analysis. J Clin Oncol. 2023;41(suppl 6):504. doi:10.1200/JCO.2023.41.6_suppl.504
3. Catto J, Tran B, Master VA, et al. Phase 2 study of the efficacy and safety of erdafitinib in patients (pts) with bacillus Calmette-Guérin (BCG)-unresponsive, high-risk non–muscle-invasive bladder cancer (HR-NMIBC) with FGFR3/2 alterations (alt) in THOR-2: Cohort 2 interim analysis results. J Clin Oncol. 2023;41(suppl 6):503. doi:10.1200/JCO.2023.41.6_suppl.503