The OncFive: Top Oncology Articles for the Week of 6/28

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 Orca-T for Matched Donor HSCT in Hematologic Malignancies

The FDA has approved allogeneic regulatory T cell-based immunotherapy with hematopoietic stem and progenitor cell (HSPC) and T cells-vldq (Tregzi; Orca-T) for use in matched donor hematopoietic stem cell transplantation (HSCT) with a myeloablative preparative regimen, for hematopoietic and immunologic reconstitution and to improve chronic graft-vs-host disease (cGHVD)–free survival, in the treatment of adults with hematological malignancies. The decision was supported by results from the phase 3 Precision-T trial (NCT05316701). In 187 patients with acute leukemias or myelodysplastic syndrome (MDS), Orca-T (n = 93) achieved a median cGFS that was not estimable (NE; 95% CI, NE-NE) vs 7.3 months (95% CI, 6.3-15.5) with unmanipulated allograft plus tacrolimus and methotrexate (n = 94; HR, 0.26; 95% CI, 0.14–0.47; P <.00001). The 12-month cumulative incidence of moderate-to-severe cGVHD was 12.6% (95% CI, 5.3%-23.1%) with Orca-T vs 44.0% (95% CI, 31.3%-56.1%) with control (HR, 0.19; 95% CI, 0.08–0.43; P=.00002), and all 88 evaluable Orca-T–treated patients achieved neutrophil recovery within 28 days of infusion. The most common adverse reactions occurring in at least 20% of patients included mucositis, diarrhea, rash, viral infections, and acute GVHD; the prescribing information carries warnings for graft failure, GVHD, infusion reactions, secondary malignancies, and transmission of infectious agents.

FDA Issues CRL to PET Diagnostic Imaging Kit for Gallium-68 Edotreotide in SSTR+ NETs

The FDA has issued a complete response letter (CRL) to the new drug application (NDA) for LNTH-2501, an investigational radioactive diagnostic kit for the preparation of gallium-68 edotreotide injection for positron emission tomography (PET) localization of somatostatin receptor (SSTR)–positive neuroendocrine tumors (NETs) in adult and pediatric patients. The letter cited unresolved third-party facility manufacturing-related conditions; no concerns about the clinical performance, safety, or efficacy data supporting the NDA were raised. The NDA was supported by results from two trials: a phase 1/2 study (NCT01619865; n = 177) in which gallium-68 edotreotide PET/CT demonstrated positive and negative agreement rates of 91% (95% CI, 85%-95%) and 89% (95% CI, 75%-96%), respectively, vs standard-of-care indium 111-pentetreotide single-photon emission computed tomography (SPECT); and a phase 2 trial (NCT01869725; n = 59 evaluable) showing positive and negative percent agreement of 92% and 75%, respectively, for reader 1. Lantheus, the developer, is working with its third-party manufacturing partner and the FDA to resolve the facility-related deficiencies. No timeline for resubmission has been announced.

FDA Grants Breakthrough Device Designation to Merlin CP-GEP for Early-Stage Melanoma Risk Stratification

The FDA has granted breakthrough device designation to Merlin CP-GEP, a clinicopathologic gene expression profile (CP-GEP) test, for risk assessment and clinical decision-making in patients with early-stage cutaneous melanoma. The designation was supported in part by the MERLIN_001 study (NCT04759781), in which 651 patients (37.0%) classified as low risk by CP-GEP had a sentinel lymph node (SLN)–positive rate of 7.1% and a negative predictive value (NPV) of 92.9% (95% CI, 90.7%-94.8%), compared with an SLN-positive rate of 23.8% in high-risk patients. The test integrates traditional clinicopathologic variables with a gene expression profiling algorithm to provide a binary high-risk/low-risk output for metastatic risk, intended to guide patient selection for SLN biopsy in the T1b/T2a cutaneous melanoma population. National Comprehensive Cancer Network guidelines support the use of the test to inform SLN biopsy selection, follow-up strategy, and shared decision-making in T1b and T2a cutaneous melanoma.

Namodenoson Meets Safety End Point in PDAC, Shows Durable Survival Outcomes Pretreated Subgroup

Updated survival analyses from a phase 2a study (NCT06387342) of namodenoson (CF102) demonstrated durable disease control and a manageable safety profile in heavily pretreated patients with advanced pancreatic ductal adenocarcinoma (PDAC), building on the agent's previously reported primary safety endpoint achievement in March 2026. Among 8 evaluable third-line patients who survived at least 2 months after treatment initiation, median overall survival (OS) exceeded 5 months, with 62.5% surviving 5 months or longer and 37.5% surviving 7 months or longer; 2 patients remained alive at the data cutoff, including 1 who received treatment for nearly 9 months. In the second-line cohort, 1 patient remained alive more than 18 months after starting namodenoson, representing the longest survivor in the study. No new safety signals were identified across second-, third-, and fourth-line populations. The toxicity profile was consistent with namodenoson's prior clinical experience in other oncologic indications. Can-Fite BioPharma plans to advance namodenoson into a phase 2b combination study with chemotherapy in PDAC.

GLP-1 Receptor Agonists, Endocrine Therapy, and Metabolic Health Comprise Holistic Breast Cancer Care

An expert discussion between Sara Nunnery, MD, MSCI, and Neil M. Iyengar, MD, aired as a Breast Cancer Briefing podcast (part 1 and part 2), addressed the growing role of glucagon-like peptide-1 receptor agonists in breast cancer survivorship, highlighting that endocrine therapy drives cardiometabolic dysfunction—including hyperinsulinemia, weight gain, and a more than doubling of diabetes-related and cardiovascular mortality risk—creating a clinical rationale for adjunctive metabolic strategies. Iyengar noted that although GLP-1 receptor agonists appear safe during endocrine therapy and in survivorship, he cautioned against initiating them during active cytotoxic chemotherapy or immunotherapy because of unknown drug interactions and the risk of compounding gastrointestinal adverse effects (AEs). Retrospective data from a single-center cohort of 75 patients with breast cancer treated at Memorial Sloan Kettering Cancer Center showed a mean relative weight loss of –5% (95% CI, –6% to –3%) at 12 months, more modest than in non-oncology phase 3 trials, and a matched cohort study of 67,591 cancer survivors found GLP-1 receptor agonist use to be linked with significantly lower all-cause mortality (HR, 0.36; 95% CI, 0.25-0.51) and no increase in recurrence risk (HR, 0.80; 95% CI, 0.50-1.30). Risk stratification beyond body mass index (BMI) is needed, as normal-weight obesity, a normal BMI with elevated body fat percentage, independently increases recurrence risk; this underscores the need for metabolic and fat-based signatures to identify at-risk patients. Iyengar emphasized that GLP-1 receptor agonists do not replace lifestyle interventions, particularly strength training to preserve muscle mass, and advocated for a slow taper of approximately 20 weeks when discontinuing to avoid weight rebound.