Melflufen study reports drug uptake in three glioblastoma patients’ tumors

Oncopeptides has reported detecting active compound in surgically removed tumors from the first three patients in its INSULA glioblastoma study, an early test of whether its peptide-drug technology can reach its intended target. The company announced the findings October 9 and presented an update October 12. The result addresses a drug-delivery question; it does not establish that treatment helps patients live longer.

The study uses melflufen, also called melphalan flufenamide, in people whose glioblastoma has returned and who are already scheduled for surgery. Its significance lies in obtaining human tissue evidence before committing to larger trials designed to measure treatment benefit.

What the study measures

Oslo University Hospital describes INSULA as a Phase 1 window-of-opportunity trial examining the drug’s concentrations and biological effects in brain tissue. Participants receive treatment before their planned operation, allowing researchers to examine the removed tumor directly.

The hospital’s study description includes assessments before surgery, tissue analysis during the operation and subsequent safety monitoring. This design can connect exposure to findings in an actual human tumor, a useful step beyond laboratory models. It also selects a specific population: patients with recurrent disease who can undergo another operation. Findings may not generalize to people who cannot have surgery.

According to Oncopeptides’ October 12 presentation, the open-label program aims to enroll approximately 10 patients and includes an optional extension for continued treatment. Three patients had undergone surgical evaluation. The company said tissue concentrations were consistent with its preclinical expectations.

Those statements remain preliminary company-reported findings. A small tissue study cannot determine whether the treatment reduces progression or improves survival, and a concentration measurement alone cannot establish a favorable balance between benefit and harm.

Delivery and clinical benefit are separate questions

Oncopeptides interprets the tissue results as evidence of blood-brain-barrier penetration. The narrower observation available to readers is that active compound was detected in the sampled tumors. How consistently the drug reaches relevant tumor regions, how much biological damage it produces there and whether that translates into meaningful disease control require further evidence.

The October 12 presentation also reported that two patients had entered the extension, with different amounts of treatment completed. Such follow-up can contribute safety observations, but a few patients cannot reliably reveal uncommon toxicity or support comparisons with established care.

The next useful evidence would include detailed tissue measurements, methods, patient-level variability and complete adverse-event reporting. A subsequent efficacy study would need clinical outcomes and an appropriate comparison to show whether the delivery finding matters to patients.

An existing drug with a consequential regulatory history

Melflufen’s established use is in multiple myeloma, a bone-marrow cancer. The European Medicines Agency lists Pepaxti as authorized for a defined previously treated population, in combination with dexamethasone. That authorization does not establish benefit in glioblastoma.

The EMA describes its action as damaging DNA and lists low platelet counts, reduced white blood cells and anemia among common adverse effects. Serious risks include pneumonia and other respiratory infections. These existing findings make careful safety assessment essential when investigating a different cancer population.

In the United States, FDA withdrew Pepaxto’s approval on February 23, 2024. The agency concluded that the required confirmatory study had not verified clinical benefit and that available evidence did not establish safety or effectiveness under the approved conditions of use.

That decision concerned multiple myeloma, rather than this brain-tumor experiment. It nevertheless illustrates why promising pharmacology and early observations must be followed by convincing clinical outcomes. INSULA currently supplies an initial delivery signal, with the therapeutic value still unresolved.