The OncFive: Top Oncology Articles for the Week of 4/5

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 Issues CRL for RP1 Plus Nivolumab in Advanced Melanoma

The FDA has issued a second complete response letter (CRL) for the biologics license application (BLA) seeking approval of vusolimogene oderparepvec (RP1) paired with nivolumab (Opdivo) in adult patients with advanced melanoma who progressed on an anti–PD-1–containing regimen, citing deficiencies in both the single-arm phase 1/2 IGNYTE trial (NCT03767348) and the phase 3 IGNYTE-3 trial (NCT06264180). Key concerns for IGNYTE included the inability to isolate RP1's individual contribution to efficacy, patient population heterogeneity, and confounded response findings. For IGNYTE-3, reasons included insufficient enrollment at the time of submission. Data from the IGNYTE trial published in the Journal of Clinical Oncology had previously revealed an overall response rate (ORR) of 32.9% (95% CI 25.2%-41.3%) in evaluable patients with confirmed progression on prior anti–PD-1 therapy (n =144) with a complete response rate of 15.0% (95% CI, 9.5%-22.0%); the median duration of response (DOR) was 33.7 months (95% CI, 14.1–not reached). This marks the second CRL for this combination following an initial rejection in July 2025; Replimune resubmitted the BLA with additional analyses after a Type A meeting with the regulatory agency.

FDA Accepts NDA for TLX101-Px Imaging Agent in Recurrent/Progressive Glioma

The regulatory agency has accepted a resubmitted new drug application (NDA) for TLX101-Px (Pixclara; Floretyrosine F 18; [18F-fluoroethyl-L-tyrosine (¹⁸F-FET)]), an investigational PET imaging agent for distinguishing recurrent or progressive glioma from treatment-related changes in adult and pediatric patients. A Prescription Drug User Fee Act (PDUFA) goal date has been set for September 11, 2026. The agent previously received orphan drug designation from the FDA in October 2020; it has also been granted fast track designation. Notably, TLX101-Px may serve a dual role as a patient selection and response assessment tool for the investigational LAT1-targeting therapeutic TLX101-Tx (iodofalan 131I), currently under evaluation in the phase 3 IPAX-BrIGHT trial (NCT07100730) in patients with recurrent glioblastoma. Distinguishing tumor progression from treatment-related change remains a critical unmet need in glioma care, and approval of this agent would expand access to an imaging modality already widely used in clinical practice internationally.

NDA Is Submitted to FDA for Neladalkib in TKI-Pretreated, Advanced, ALK+ NSCLC

Nuvalent has submitted an NDA to the FDA for neladalkib (NVL-655) for patients with TKI-pretreated, advanced, ALK-positive non–small cell lung cancer (NSCLC), supported by data from the phase 1/2 ALKOVE-1 trial (NCT05384626). Among patients who received neladalkib following any previous ALK TKI with or without chemotherapy (n = 253), the ORR was 31% (95% CI, 26%-37%); the ORR in TKI-pretreated, lorlatinib (Lorbena)-naive patients (n = 63) was 46% (95% CI, 33%-59%). The respective 18-month DOR rates were 53% (95% CI, 34%–68%) and 60% (95% CI, 19%–85%). Particularly notable activity was observed in patients with G1202R mutations who were TKI pretreated and lorlatinib naive (n = 12), with an ORR of 83% (95% CI, 52%-98%). The 18-month DOR rate was 77% (95% CI, 34%-94%). Among patients with measurable central nervous system (CNS) lesions who were TKI pretreated and lorlatinib naive (n = 24), the intracranial ORR was 63% (95% CI, 41%-81%) with an 18-month intracranial DOR rate of 92% (95% CI, 57%-99%). Full data from ALKOVE-1 are planned for presentation at a future medical meeting.

Gynecologic Oncologists Preview the Abstracts Set to Drive Conversation at SGO 2026

The SGO Annual Meeting on Women's Cancer, taking place April 10-13, 2026 in San Juan, Puerto Rico, will feature several highly anticipated presentations spanning gynecologic malignancies. Leading highlights include the final overall survival (OS) analysis of the phase 3 ROSELLA trial (NCT05257408) of relacorilant (Lifyorli) plus nab-paclitaxel (Abraxane) in platinum-resistant ovarian cancer, as well as an encore presentation of final analysis results from the phase 3 KEYNOTE-B96 trial (NCT05116189) evaluating pembrolizumab (Keytruda) plus weekly paclitaxel with or without bevacizumab (Avastin) in the same setting. Additional sessions of interest include results from the phase 2 GOG-3039 trial (NCT04393285) evaluating abemaciclib (Verzenio) plus letrozole in recurrent endometrioid endometrial carcinoma, and data from the phase 3 NRG-GY019 trial (NCT04095364) comparing letrozole alone vs paclitaxel and carboplatin followed by letrozole in first-line low-grade serous ovarian cancer. For more anticipated abstracts, sign up to access this exclusive preview.

ASCO Thyroid Cancer Guideline Updates Synthesize Evidence-Based Systemic Therapy Recommendations

ASCO published updated evidence-based clinical practice guidelines for systemic therapy across thyroid cancer subtypes on April 1, 2026, providing structured treatment recommendations stratified by disease histology, line of therapy, and genomic profile. For radioactive iodine–refractory well-differentiated thyroid cancer, lenvatinib (Lenvima) is recommended as the preferred first-line multikinase inhibitor over sorafenib (Nexavar) based on available efficacy data, with cabozantinib (Cabometyx) recommended in subsequent lines; genomically targeted therapies are strongly recommended for tumors with NTRK, RET, or BRAF V600E alterations using agents including larotrectinib (Vitrakvi), entrectinib (Rozlytrek), selpercatinib (Retevmo), dabrafenib (Tafinlar), and trametinib (Mekinist). For more updates, sign up to access this exclusive resource.