iOnctura Broadens PI3K Inhibitor Program to NSCLC

Following a successful funding round that raised nearly $86 million, Swiss biopharma company iOnctura is set to evaluate its leading drug candidate, roginolisib, in non-small cell lung cancer (NSCLC). The clinical program's expansion is supported by new partnerships with ETOP IBCSG Partners Foundation and GSK, as mentioned in a press release dated 9 July.

iOnctura's strategy involves a Phase II clinical study that will explore the efficacy of roginolisib when combined with GSK's PD-1 inhibitor, Jemperli (dostarlimab). This combination therapy targets NSCLC patients who have shown resistance to first-line checkpoint inhibitor treatments, potentially with or without docetaxel.

Roginolisib functions as an allosteric modulator of phosphoinositide 3-kinase-δ (PI3Kδ), a protein recognized for its central role in cancer progression. By inhibiting PI3Kδ, the drug triggers an anti-tumor immune response, effectively mobilizing the body's defense mechanisms against cancer cells. Earlier this year, the U.S. Food and Drug Administration (FDA) granted roginolisib orphan drug designation, highlighting its potential in treating rare medical conditions.

The decision to pair roginolisib with GSK's PD-1 inhibitor is based on emerging clinical and biomarker data, which suggest that the combination could counteract or even reverse drug resistance in NSCLC. According to iOnctura, this enhanced anti-tumor immune activity is achieved without adding significant toxicity.

Roginolisib is currently undergoing a Phase I clinical trial (NCT04328844) that assesses its effects as a monotherapy and in combination with chemotherapy in patients with advanced or metastatic cancers, including metastatic uveal melanoma. Preliminary results have shown positive efficacy at the 80mg dose, with minimal adverse events (grade 1 and 2) reported among patients with solid tumors.

Catherine Pickering, CEO of iOnctura, stated, “The successful uveal melanoma data reported so far, combined with a rich preclinical data package, support the rationale to expand our development program with potentially synergistic combinations in NSCLC.”

However, challenges in the development of PI3K inhibitors have emerged in recent years. The FDA’s Oncologic Drugs Advisory Committee (ODAC) expressed concerns about the safety profile of these drugs, citing high levels of fatal adverse events and toxicity. Consequently, the FDA recommended that future approvals for PI3K inhibitors in hematologic malignancies should require data from randomized trials, a decision made in 2022.

Despite these setbacks, advancements in the PI3K inhibitor space continue. Roche recently secured FDA priority review for inavolisib, another PI3K inhibitor, as a combination therapy with fulvestrant and Pfizer’s Ibrance (palbociclib) for breast cancer.

Earlier this year, iOnctura successfully raised €80m ($85.8m) in Series B financing. This substantial funding will support Phase II clinical activities for both roginolisib and the company's other candidate, cambritaxestat, an autotaxin inhibitor.

By expanding its clinical program and securing significant financial backing, iOnctura aims to push the boundaries of cancer treatment, focusing on novel therapeutic combinations that could offer new hope to patients with resistant forms of cancer.