The OncFive: Top Oncology Articles for the Week of 8/9

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 Approves Iberdomide (Zenbexus) Plus Daratumumab/Dexamethasone for Relapsed/Refractory Multiple Myeloma

The FDA has granted accelerated approval to iberdomide (Zenbexus) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone (IberDd) for adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior line of therapy that included a proteasome inhibitor and an immunomodulatory agent. The decision was supported by the phase 3 EXCALIBER-RRMM trial (NCT04975997), which compared IberDd with daratumumab plus bortezomib (Velcade) and dexamethasone (DVd) and featured dual primary end points of minimal residual disease (MRD) negativity and progression-free survival (PFS). Patients in the IberDd arm (n = 207) achieved an MRD-negative complete response rate at any time of 41% (95% CI, 34%-48%) compared with 21% (95% CI, 15%-27%) in the DVd arm (P < .0001). Adverse effects (AEs) led to treatment discontinuation in 7.8% of IberDd-treated patients, and the most common any-grade AEs included neutropenia (90.2%) and infections (78.9%). Serious AEs occurring in at least 2% of IberDd recipients included pneumonia (26%), second primary malignancy (5.9%), and febrile neutropenia (3.9%), and the trial remains ongoing for PFS.

FDA Issues Complete Response Letter to 177Lu-Edotreotide (ITM-11) for GEP-NETs

The FDA has issued a complete response letter (CRL) to the new drug application (NDA) seeking approval of the radiotherapeutic 177Lu-edotreotide (ITM-11) for patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), citing Chemistry, Manufacturing and Controls items and third-party commercial facility issues rather than any clinical safety or efficacy concerns. The application was supported by the phase 3 COMPETE trial (NCT03049189), which evaluated 177Lu-edotreotide vs everolimus (Afinitor) in patients with unresectable, progressive grade 1 or 2 GEP-NETs. The median PFS per blinded independent central review (BICR) was 23.9 months (95% CI, 18.7-30.0) in the 177Lu-edotreotide arm (n = 207) vs 14.1 months (95% CI, 9.2-20.9) in the everolimus arm (n = 102; hazard ratio [HR], 0.67; 95% CI, 0.48-0.95; P = .022). Interim overall survival (OS) numerically favored 177Lu-edotreotide at 63.4 months vs 58.7 months, although this difference was not yet statistically significant (HR, 0.78; 95% CI, 0.5-1.1; P = .206). ITM did not receive a request for additional clinical or nonclinical data and is reviewing the agency’s comments toward a potential NDA resubmission, while 177Lu-edotreotide continues to be evaluated in the phase 3 COMPOSE study (NCT04919226).

Zipalertinib Plus Chemotherapy Improves PFS in First-Line EGFR Exon 20 Insertion–Positive NSCLC

Zipalertinib plus platinum-based chemotherapy met the primary end point of PFS vs chemotherapy alone at a planned interim analysis of the phase 3 REZILIENT3 trial (NCT05973773) in patients with previously untreated, locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. The improvement was statistically significant and clinically meaningful, prompting an Independent Data Monitoring Committee to recommend unblinding the study, with full data to be presented at a future international medical meeting. In the open-label trial, patients were randomly assigned 1:1 to receive zipalertinib plus pemetrexed and cisplatin or carboplatin or chemotherapy alone, with PFS by BICR as the primary end point and secondary end points including OS and objective response rate (ORR). Zipalertinib is an oral, irreversible EGFR inhibitor designed to target exon 20 insertion variants while sparing wild-type EGFR, and it previously received FDA breakthrough therapy designation. Cullinan Therapeutics and Taiho Oncology intend to pursue first-line US approval, separate from an accepted NDA for zipalertinib monotherapy in the pretreated setting—with or without amivantamab-vmjw (Rybrevant)—based on the phase 1/2 REZILIENT1 trial (NCT04036682), which carries a target action date of February 27, 2027.

Divesiran (SLN124) Meets Primary Response End Point in Phlebotomy-Dependent Polycythemia Vera

Divesiran (SLN124), a first-in-class short interfering RNA (siRNA) therapy, met the primary end point of the phase 2 portion of the SANRECO trial (NCT05499013) by significantly increasing the proportion of clinical responders vs placebo in patients with phlebotomy-dependent polycythemia vera (PV). A response—defined as the absence of phlebotomy and maintenance of hematocrit below 45% during weeks 18 to 36—was achieved by 88% of divesiran-treated patients vs 19% of those given placebo (placebo-adjusted response rate, 69%; P < .0001), with rates of 93.8% and 81.3% for the 6-mg/kg dose given every 6 or 12 weeks, respectively. The trial also met its key secondary end point of phlebotomy rate during weeks 0 to 36, with a mean of 0.2 phlebotomies per patient in the divesiran groups vs 2.1 with placebo (P < .0001). Divesiran was well tolerated, with infrequent, self-limiting injection site reactions and 2 investigator-reported cases of grade 1 anemia among the 48 patients in the phase 2 portion. The agent silences TMPRSS6 to increase hepcidin and restrict marrow iron availability, holds FDA fast track and orphan drug designations in PV, and is slated to enter a phase 3 trial of every-12-week dosing in the first half of 2027.

Phase 3 VERSATILE-003 Trial of PDS0101 in HNSCC Is Discontinued

PDS Biotechnology will discontinue internal funding of the phase 3 VERSATILE-003 trial (NCT06790966), which is evaluating the investigational immunotherapy PDS0101 in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), and will instead seek partnerships or external financing to continue that program. The company is redirecting its resources toward PDS0301, a tumor-targeted interleukin-12 immunocytokine, in metastatic colorectal cancer (CRC). In a phase 2 interim analysis (NCT05286814) conducted with the National Cancer Institute, PDS0301 plus hepatic artery infusion pump therapy produced a 71% ORR at 6 months and an 80% 24-month OS rate in patients with metastatic microsatellite stable and mismatch repair–proficient CRC with liver metastases. PDS0301 has been evaluated in more than 380 treated patients across monotherapy, doublet, and triplet combinations, with the company reporting an encouraging safety and tolerability profile. A randomized phase 2b trial designed with FDA feedback is planned, and over the next 18 to 24 months PDS Biotechnology intends to advance PDS0301 while assessing strategic partnering opportunities for PDS0101.