The first patient has been enrolled in Oncopeptide’s clinical “Window-of-Opportunity” (WoO) study, OP-701 (INSULA), evaluating the company’s proprietary Peptide Drug Conjugate (PDC) platform in glioblastoma.
This milestone marks the transition from preclinical development to early clinical assessment of PDCs in the context of brain cancer, with the potential to expand the technology’s application beyond its established role in multiple myeloma.
Background and Rationale
Glioblastoma (GBM) remains the most aggressive and lethal primary brain tumor in adults, characterized by rapid progression, therapeutic resistance, and a median survival of only 12–15 months despite current therapies.[1]. Traditional oncological agents largely fail to achieve therapeutic concentrations in the central nervous system due to the restrictive nature of the blood-brain barrier (BBB)[2]. Consequently, there is a significant unmet medical need for novel therapeutic strategies to effectively target malignant cells in the brain.
Peptide Drug Conjugates (PDCs) are an emerging therapeutic class specifically engineered to overcome the BBB and deliver cytotoxic agents directly to tumor cells[3].
Oncopeptides’ PDC molecules leverage their small size and lipophilicity to enhance BBB penetration, with the peptide carrier component designed to exploit cancer cell metabolism to selectively activate and accumulate cytotoxic metabolites in malignant tissue. This targeted approach aims to maximize therapeutic effect while minimizing toxicity to healthy brain tissue, a limitation commonly encountered with traditional systemic chemotherapies.
Study Design
The OP-701 (INSULA) WoO study is the first clinical investigation of a PDC in glioblastoma. Approximately 10 patients with recurrent GBM scheduled for surgical intervention will be enrolled at Oslo University Hospital in Norway.
The trial employs an innovative design in which an approved PDC from Oncopeptides’ platform serves as a “clinical probe.” This design enables direct measurement of drug activity within resected tumor tissue, allowing rapid assessment of BBB penetration and cytotoxic efficacy in situ.
“Enrolling the first patient in our glioblastoma study is an important step that shifts our brain cancer program from pre-clinical and a regulatory milestone to active clinical assessment. Following our swift regulatory approval, this trial allows us to efficiently generate human clinical data in a highly underserved indication, potentially demonstrating the true versatility of our PDC platform as we look to expand our pipeline beyond multiple myeloma,” noted Sofia Heigis, MSc, Chief Executive Officer of Oncopeptides,
Scientific and Clinical Implications
The primary objective of the OP-701 study is to obtain initial human proof of concept that Oncopeptides’ PDCs can successfully traverse the BBB in patients with glioblastoma and exert cytotoxic effects on tumor cells. By employing a focused WoO approach, the study is designed to validate the biological mechanism of action and provide key insights before advancing to dose-finding and larger-scale clinical trials.
Given the estimated global glioblastoma market exceeding $8 billion USD by 2035 [4], the development of novel, BBB-penetrant therapeutics such as PDCs could represent a paradigm shift in the management of this devastating disease. The wide therapeutic window of PDCs, enabled by their targeted design, offers the promise of improved benefit-risk profiles and enhanced treatment outcomes for patients with GBM.
Next steps
The initiation of the OP-701 WoO study marks a significant advancement in the clinical development of PDCs for glioblastoma. Should the trial demonstrate effective BBB penetration and tumor-selective cytotoxicity, Oncopeptides’ PDC platform may offer a new avenue for addressing the profound unmet medical need in glioblastoma therapy.
Reference
[1] Ostrom QT, Cioffi G, Gittleman H, et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2016–2020. Neuro Oncol. 2023;25(Suppl 2):iii1–iii53.
[2] Arvanitis CD, Ferraro GB, Jain RK. The blood–brain barrier and blood–tumour barrier in brain tumours and metastases. Nat Rev Cancer. 2020;20(1):26–41.
[3] Stupp R, Mason WP, van den Bent MJ, et al. Peptide–drug conjugates as a targeted therapy for glioblastoma: Current status and future prospects. Expert Opin Investig Drugs. 2024;33(2):123–130.
Insight Partners. Glioblastoma Multiforme Market Forecast to 2035. Market Analysis Report. 2025.
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