The OncFive: Top Oncology Articles for the Week of 4/19

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:

Perioperative Pembrolizumab Plus Enfortumab Vedotin Nets FDA Priority Review in Cisplatin-Eligible MIBC

The FDA has granted priority review to two supplemental biologics license applications (sBLAs) seeking approval of enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) or subcutaneous pembrolizumab (Keytruda Qlex) for the perioperative treatment of patients with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin-based chemotherapy. A Prescription Drug User Fee Act (PDUFA) target action date has been set to August 17, 2026. The sBLAs are supported by findings from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124), in which patients who received enfortumab vedotin plus pembrolizumab (n = 405) had a median event-free survival (EFS) that was not reached (95% CI, not reached [NR]-NR) vs 48.5 months (95% CI, 43.3-NR) with cisplatin plus gemcitabine (n = 403; HR 0.53; 95% CI, 0.41-0.70; 1-sided P <.0001); the 24-month EFS rates were 79.4% and 66.2%, respectively. Grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 75.7% vs 67.2% of those in the investigational and chemotherapy arms, respectively. Enfortumab vedotin plus pembrolizumab or subcutaneous pembrolizumab was previously cleared by the regulatory agency in November 2025 as neoadjuvant treatment followed by adjuvant treatment after cystectomy for patients with cisplatin-ineligible MIBC, based on data from the phase 3 EV-303/KEYNOTE-905 trial (NCT03924895).

FDA Extends Review Period for Subcutaneous Isatuximab BLA in Multiple Myeloma

The FDA has extended its review of the biologics license application (BLA) for subcutaneous isatuximab-irfc (Sarclisa) delivered via an on-body injector (OBI) for patients with multiple myeloma, with a revised target action date of July 23, 2026. If approved, isatuximab would become the first anticancer therapy approved by the FDA for OBI delivery. The BLA is supported by findings from the phase 3 IRAKLIA trial (NCT05405166), in which subcutaneous isatuximab (n = 263) showed noninferior efficacy vs intravenous (IV) isatuximab (n = 268) when each was combined with pomalidomide (Pomalyst) and dexamethasone. Overall response rates (ORRs) in the respective arms were 71.1% and 70.5% (relative risk [RR], 1.008; 95% CI, 0.903-1.126; P =.0006) and very good partial response (VGPR) or better rates were 46.4% and 45.9%. Noninferiority in pharmacokinetic exposure was also confirmed, with a geometric mean ratio for C_trough at steady state of 1.532 (90% CI, 1.316-1.784). Notably, infusion-related reactions (IRRs) were markedly lower with subcutaneous delivery (1.5% vs 25.0%; RR, 0.061; 95% CI, 0.022-0.164), with OBI-related TEAEs of any grade occurring in only 3.4% of patients.

Pembrolizumab-Based Combinations Miss the Mark in Frontline ccRCC

The phase 3 LITESPARK-012 trial (NCT04736706) did not meet its dual primary end points of progression-free survival (PFS) and overall survival (OS), as neither pembrolizumab (Keytruda) plus lenvatinib (Lenvima) and belzutifan (Welireg), nor coformulated pembrolizumab/quavonlimab (MK-1308A) combined with lenvatinib, improved progression-free survival (PFS) or overall survival (OS) vs pembrolizumab plus lenvatinib in patients with treatment-naive advanced clear cell renal cell carcinoma (ccRCC). The open-label, randomized trial enrolled adult patients with advanced ccRCC who had not previously received systemic therapy for advanced disease. Pembrolizumab was administered at 400 mg once every 6 weeks for up to 18 administrations, belzutifan and lenvatinib were given orally once daily at 120 mg and 20 mg, respectively, and the pembrolizumab/quavonlimab coformulation consisted of pembrolizumab at 400 mg plus quavonlimab at 25 mg every 6 weeks. Toxicity profiles for both investigational combinations were consistent with those previously reported for the individual agents. The LITESPARK-012 findings do not affect other ongoing studies within the LITESPARK clinical program. A full evaluation of the data is ongoing, with Merck and Eisai planning to share results with the scientific community.

Daraxonrasib Demonstrates First-Line Activity With/Without Chemotherapy in Metastatic PDAC

Two phase 1/2 datasets (NCT05379985; NCT06445062) presented at the 2026 AACR Annual Meeting revealed that daraxonrasib (RMC-6236) showed antitumor activity numerically exceeding historical chemotherapy benchmarks in first-line metastatic pancreatic ductal adenocarcinoma (PDAC). When given as monotherapy in efficacy-evaluable patients with RAS-mutant metastatic PDAC (n = 38), daraxonrasib elicited an ORR of 47% (95% CI, 31%-64%) and a disease control rate (DCR) of 92% (95% CI, 79%-98%); the Kaplan-Meier–estimated 6-month PFS and OS rates were 71% (95% CI, 53%-83%) and 83% (95% CI, 67%-92%), respectively, in the all–RAS-mutant population (n = 40). In combination with gemcitabine and nab-paclitaxel (Abraxane) in the GI-102 Platform Study (n = 40), daraxonrasib induced an ORR of 58% (95% CI, 41%-73%), a DCR of 90% (95% CI, 76%-97%), and 6-month PFS and OS rates of 84% (95% CI, 68%-93%) and 90% (95% CI, 76%-96%), respectively. These datasets support the ongoing global phase 3 RASolute 303 trial (NCT07491445) examining daraxonrasib with or without chemotherapy vs chemotherapy alone as first-line treatment for patients with metastatic PDAC, with findings from the phase 3 RASolute 302 trial (NCT06625320) in the second-line setting planned for presentation at the 2026 ASCO Annual Meeting.

Tovorafenib Approved in Europe for BRAF-Altered R/R Pediatric Low-Grade Glioma

The European Commission has granted conditional marketing authorization to tovorafenib (Ojemda) for use in patients at least 6 months of age with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion, rearrangement, or V600 mutation after at least 1 prior systemic therapy, making it the first systemic therapy indicated specifically for pLGG with BRAF rearrangements across all 27 European Union member states. The decision was supported by findings from the phase 2 FIREFLY-1 trial (NCT04775485; n = 137), which demonstrated an ORR of 71% per Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria and 53% per Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria, with a median duration of response of 18.0 months and a median time to response of 5.4 months per RAPNO-LGG criteria. Updated 3-year data showed a median time to next treatment of 42.6 months (95% CI, 36.7-not evaluable), with 77% of 39 patients who entered a post-treatment observation period remaining treatment free for at least 12 months. Grade 3 or higher treatment-related adverse effects (TRAEs) occurred in 66% of patients, most commonly decreased growth velocity (34%), anemia (14%), and increased creatine phosphokinase levels (11%); the treatment discontinuation rate was 13%. Tovorafenib previously received accelerated approval from the FDA in 2024 for the same indication based on findings from FIREFLY-1.