Study Background

This Phase 1/2 clinical trial evaluates the safety and optimal dosage of selincro in combination with standard radiation therapy for newly diagnosed DIPG and high-grade glioma patients with H3 K27M mutations. Current radiation therapy alone provides limited tumor reduction, necessitating new treatment combinations.

Disease Characteristics

DIPG is located in the brainstem and is inoperable, while high-grade glioma grows rapidly, resulting in a very poor prognosis. In particular, the H3 K27M mutation increases the malignancy of the tumor, and the current standard treatment is limited to radiation. The development of effective drugs for this high-risk group can significantly improve patient survival rates.

Selincro Mechanism

Selincro is a selective nuclear export inhibitor that blocks CRM1 (nuclear export protein), inhibiting the growth signals of cancer cells and inducing cell death. When used in combination with radiation therapy, it may interfere with DNA damage repair, potentially increasing the death of tumor cells.

Trial Design

The trial is divided into Part 1 (dose-escalation phase) and Part 2 (efficacy evaluation phase). In Part 1, the maximum tolerated dose (MTD) is determined, and in Part 2, the anti-cancer effect of that dose is confirmed. Both phases use the same radiation protocol and focus only on differences in selincro dosage.

Expected Outcomes

If successful, the combination of selincro and radiation may become a new standard treatment for DIPG and HGG patients with limited current treatment options. It may also expand the clinical applicability of nuclear export inhibitors and have a ripple effect on other CNS tumors.