The OncFive: Top Oncology Articles for the Week of 11/16

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:

FDA Grants Accelerated Approval to Sevabertinib in HER2-Mutated Nonsquamous NSCLC

The FDA has awarded accelerated approval to sevabertinib (Hyrnuo) for use in adults with locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring HER2 (ERBB2) TKD activating mutations after prior systemic therapy, based on results from the phase 1/2 SOHO-01 trial (NCT05099172). In patients with nonsquamous NSCLC and HER2 TKD mutations who had prior systemic therapy but were naive to HER2-targeted therapy (n = 70), sevabertinib induced an objective response rate (ORR) of 71% (95% CI, 59%-82%) with a median duration of response (DOR) of 9.2 months (95% CI, 6.3-15.0). In those who received prior treatment, including HER2-targeted antibody-drug conjugates (n = 52), the ORR was 38% (95% CI, 25%-53%) and the median DOR was 7.0 months (95% CI, 5.6-not evaluable [NE]). Across escalation, expansion, and extension cohorts, sevabertinib showed a manageable safety profile with cases of diarrhea, rash, and paronychia.

FDA Approves Perioperative Enfortumab Vedotin Plus Pembrolizumab for Cisplatin-Ineligible MIBC

The FDA cleared enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) as neoadjuvant therapy followed by adjuvant treatment after cystectomy for patients with cisplatin-ineligible muscle-invasive bladder cancer (MIBC). The decision was supported by findings from the phase 3 EV-303/KEYNOTE-905 trial (NCT03924895), which indicated that the combination significantly improved event-free survival (EFS) vs radical cystectomy plus pelvic lymph node dissection (RC + PLND) alone; the median EFS was not reached (NR; 95% CI, 37.3-NR) and 15.7 months (95% CI, 10.3-20.5), respectively (HR, 0.40; 95% CI, 0.28-0.57; P < .0001). Moreover, the median overall survival (OS) was NR (95% CI, NR-NR) in the investigative arm vs 41.7 months (95% CI, 31.8-NR) in the control arm (HR, 0.50; 95% CI, 0.33-0.74; P = .0002). Safety data showed higher rates of grade 3 or higher treatment-emergent toxicities (71.3%) with the combination, but it offers a new standard for cisplatin-ineligible MIBC in both the neoadjuvant and adjuvant settings.

FDA Approves Selumetinib for Adult NF1-Associated Plexiform Neurofibromas

The FDA also approved selumetinib (Koselugo) for the treatment of adult patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN). Findings from the phase 3 KOMET trial (NCT04924608) demonstrated a confirmed ORR of 20% (95% CI, 11%-31%) with selumetinib vs 5% (95% CI, 2%-13%) with placebo (P = .011), with 86% of responders maintaining a response for at least 6 months. Safety results showed expected MEK inhibitor–associated adverse effects (AEs) like dermatitis acneiform, elevated creatine phosphokinase, diarrhea, nausea, and transaminase elevations. This approval follows the 2025 clearance of selumetinib granules and capsules for pediatric patients.

FDA Grants Full Approval to Tarlatamab for Extensive-Stage Small Cell Lung Cancer

The regulatory agency granted traditional approval to tarlatamab-dlle (Imdelltra) for use in adults with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy, based on data from the phase 3 DeLLphi-304 study (NCT05740566). Here, tarlatamab significantly improved OS to 13.6 months (95% CI, 11.1-NE) vs 8.3 months (95% CI, 7.0-10.2) with standard chemotherapy (HR, 0.60; 95% CI, 0.47-0.77; P < .001). Additionally, the median progression-free survival achieved with tarlatamab was higher than that observed with chemotherapy, at 4.2 months (95% CI, 3.0-4.4) and 3.2 months (95% CI, 2.9-4.2), respectively (HR, 0.72; 95% CI, 0.59-0.88; P < .001). Safety data revealed high rates of cytokine release syndrome, mostly grade 1/2 in severity, during early cycles, but fewer grade 3 or higher treatment-related AEs, dose interruptions, and discontinuations vs chemotherapy. The full approval follows the drug’s May 2024 accelerated approval based on the phase 2 DeLLphi-301 study (NCT05060016).

FDA Approves Daratumumab and Hyaluronidase-fihj in Newly Diagnosed Light Chain Amyloidosis

The FDA also granted full approval to daratumumab and hyaluronidase-fihj (Darzalex Faspro) in combination with bortezomib (Velcade), cyclophosphamide, and dexamethasone (D-VCd) for use in patients with newly diagnosed light chain (AL) amyloidosis, converting its January 2021 accelerated approval. The decision is based on data from the phase 3 ANDROMEDA study (NCT03201965), where D-VCd (n = 195) resulted in an improved hematologic complete response (HemCR) rate vs VCd alone (n = 193) in this population, at 42% and 13%, respectively (P < .0001); the median time to HemCR was 59 days (range, 8-299). Moreover, the hematologic very good partial response or better rates were 78% and 49% in the respective arms. The hazard ratio for major organ deterioration PFS (MOD-PFS) was 0.58 (95% CI, 0.37-0.92). At a median follow-up of 61.4 months, the HR for MOD-PFS was 0.47 (95% CI, 0.33-0.67; P < .0001). Safety data demonstrated expected toxicities, including diarrhea, peripheral edema, neuropathy, infections, and cytopenias, with grade 3/4 effects like lymphopenia, pneumonia, and cardiac failure occurring in both arms.

Honorable Mentions

• A rolling submission of a new drug application (NDA) to the FDA seeking the accelerated approval of zipalertinib for use in patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who have received prior platinum-based systemic chemotherapy has been initiated.
• The FDA has accepted for review an NDA seeking the approval of zidesamtinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC who previously received at least 1 ROS1 TKI.
• An NDA seeking the approval of gedatolisib (PF-05212384) for use in patients with hormone receptor–positive, HER2-negative advanced breast cancer has also been submitted to the FDA for review.