The OncFive: Top Oncology Articles for the Week of 8/16

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

NDA Is Submitted for UGN-103 for Recurrent Low-Grade Intermediate-Risk NMIBC

A new drug application (NDA) has been submitted to the FDA seeking approval of UGN-103 (mitomycin) for intravesical solution in adult patients with recurrent low-grade intermediate-risk non–muscle-invasive bladder cancer (LG-IR-NMIBC). The submission is supported by results from the ongoing single-arm, multicenter phase 3 UTOPIA trial (NCT06331299), in which UGN-103 (n = 99) elicited a 3-month complete response (CR) rate of 77.8% (95% CI, 68.3%-85.5%) and a 6-month duration of response (DOR) rate of 94.5% by Kaplan-Meier estimate (95% CI, 86.1%-97.9%). UGN-103 is designed to offer improvements over UGN-102 (Zusduri), which was the first and only FDA-approved treatment for recurrent low-grade intermediate-risk NMIBC based on data from the phase 3 ENVISION trial (NCT05243550). Potential improvements include a shorter manufacturing process, simplified reconstitution, and extended shelf-life. Patients in UTOPIA received UGN-103 at a dose of 75 mg once weekly for 6 weeks for 6 total doses; 3-month CR rate served as the primary end point. Secondary end points included DOR, durable CR rate, safety, and mitomycin plasma concentrations.

Intismeran Autogene Plus Pembrolizumab Meets RFS and DMFS End Points in Resected Stage IIB-IV Melanoma

Adjuvant intismeran autogene (V940; mRNA-4157), an individualized neoantigen therapy, plus pembrolizumab (Keytruda) significantly improved recurrence-free survival (RFS) and distant metastasis–free survival (DMFS) vs pembrolizumab alone in patients with completely resected stage IIB to IV cutaneous melanoma, meeting the primary end point of RFS and the key secondary end point of DMFS at a prespecified interim analysis of the phase 3 INTerpath-001 trial (NCT05933577). The trial randomly assigned 1137 disease-free patients in a 2:1 fashion to receive intismeran autogene at 1 mg intramuscularly every 3 weeks for up to 9 doses plus pembrolizumab at 400 mg intravenously every 6 weeks for up to 9 cycles, or placebo plus pembrolizumab on the same schedule. Overall survival (OS) was not yet mature at the time of the analysis. The safety profiles of both agents were consistent with what has previously been reported, with no new safety signals identified. These results build on 5-year follow-up data from the phase 2b KEYNOTE-942/mRNA-4157-P201 trial (NCT03897881), which showed the combination reduced the risk of recurrence or death by 49% (HR, 0.51; 95% CI, 0.294-0.887) and the risk of distant metastasis or death by 59% (HR, 0.411; 95% CI, 0.200-0.843) vs pembrolizumab alone.

T-DXd Improves PFS in First-Line HER2-Mutant NSCLC

Frontline fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs standard of care in patients with unresectable, locally advanced, or metastatic HER2-mutant nonsquamous non–small cell lung cancer (NSCLC), according to topline data from the phase 3 DESTINY-Lung04 trial (NCT05048797). A consistent safety profile with T-DXd was reported. The trial randomly assigned treatment-naive patients with HER2 exon 19 or exon 20 mutations in a 1:1 fashion to T-DXd or platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab. Stratification factors included smoking history and brain metastases. The primary end point was PFS by blinded independent central review. T-DXd was approved in 2022 for previously treated advanced HER2-mutant NSCLC and across several breast cancer settings, including the May 2026 approval for early-stage HER2-positive disease based on the phase 3 DESTINY-Breast11 trial (NCT05113251). DESTINY-Lung04 will continue to examine secondary end points including OS, with data expected at an upcoming meeting.

FDA Awards Fast Track Designation to Safusidenib in IDH1-Mutant Glioma

The FDA has granted fast track designation to safusidenib for patients with IDH1-mutant glioma. The decision was supported by findings from the safusidenib clinical development program, which included updated long-term follow-up data from the phase 2 J201 study (NCT04458272) conducted in patients with chemotherapy- and radiotherapy-naive grade 2 IDH1-mutant glioma. At a median follow-up of 38.8 months, patients who received safusidenib (n = 27) achieved a confirmed objective response rate (cORR) of 51.9%, a median PFS that was not reached, and a 36-month PFS rate of 79.1%, with 1 responder experiencing disease progression. No new safety signals were identified. Patients in J201 received safusidenib at 250 mg twice daily on a continuous dosing schedule. cORR per independent review committee and treatment-emergent adverse effects (TEAEs) served as primary end points. The designation arrives as the pivotal phase 3 SIGMA study (NCT05303519) continues enrolling, examining safusidenib vs placebo as maintenance therapy after standard of care in patients with IDH1-mutant, high-risk astrocytoma. Safusidenib is also being examined in the phase 3 G307 trial (NCT07712757) in regions where vorasidenib (Voranigo) is not yet accessible, and the phase 2 G209 trial (NCT07703436) in grade 2 or 3 IDH1-mutant glioma that has progressed after vorasidenib.

FDA Grants Fast Track Designation to PLN-101095 Plus Pembrolizumab in Solid Tumors

The FDA has awarded fast track designation to PLN-101095 paired with pembrolizumab for patients with solid tumors resistant to immune checkpoint inhibitors (ICIs). In the phase 1a/1b FORTIFY trial (NCT06270706), previously reported results showed that among patients treated at the 1000-mg twice-daily dose (n = 6), 3 experienced clinical responses, with 1 additional response achieved at the 2000-mg dose (n = 3). Among those with ICI–secondary refractory disease across the 3 highest dose levels (n = 10), 1 confirmed CR and 3 partial responses were reported. Responses were observed in patients with cholangiocarcinoma, head and neck squamous cell carcinoma, melanoma, and NSCLC. The disease control rate was 60%. Among all evaluable patients (n = 16), the most common TEAEs were rash (50%), diarrhea (19%), and anemia (19%); 31% of patients experienced serious TEAEs. With fast track designation now in place, FORTIFY will progress toward additional results expected in 2027.