iOnctura has reported immune-cell changes with roginolisib combinations in patients with advanced non-small cell lung cancer resistant to immunotherapy.

iOnctura has reported changes in immune-cell activity following treatment with its investigational PI3Kδ inhibitor roginolisib in patients with immunotherapy-resistant non-small cell lung cancer (NSCLC).

Data from the Phase 1/2 PULMO-01 study, presented at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting, showed that roginolisib-containing combinations reduced activated regulatory T cells (Tregs) and increased stem-like CD8+ T cells.

The findings suggest that inhibiting PI3Kδ signalling could help reverse the immunosuppressive environment that allows some tumours to evade immune checkpoint inhibitors.

The trial enrolled 49 patients with advanced or metastatic non-squamous NSCLC whose disease had progressed following treatment with immune checkpoint inhibitors.

Patients were randomised across three treatment groups: roginolisib, the checkpoint inhibitor dostarlimab and chemotherapy drug docetaxel (triplet combination, n=16); roginolisib plus dostarlimab without chemotherapy (n=17); or dostarlimab plus docetaxel (control, n=16).

Chemo-free combination shows strongest immune-cell changes

In both treatment groups receiving roginolisib, researchers observed reductions in activated Tregs and increases in stem-like TCF1-positive CD8+ central memory T cells.

These changes were most pronounced and sustained in patients receiving roginolisib and dostarlimab without chemotherapy.

Tregs normally help regulate immune responses, but their activity within the tumour microenvironment can suppress anti-tumour immunity. Increasing populations of stem-like CD8+ T cells may also help sustain immune responses against cancer.

Roginolisib is a conformation-selective inhibitor of phosphoinositide 3-kinase delta (PI3Kδ), an enzyme involved in immune-cell signalling. The drug is designed to lock PI3Kδ into its inactive state, reducing signalling associated with immunosuppression.

Catherine Pickering, chief executive officer and co-founder of iOnctura, said: “Resistance to immunotherapy remains one of the greatest challenges in the treatment of advanced NSCLC. These data show that roginolisib reduces immunosuppressive Tregs, which are linked to resistance in patients whose cancer no longer responds to checkpoint inhibitors. The strongest immune effects came with the ‘chemo-free’ regimen, which was also the most tolerable. These results support a potential future chemo-free treatment regimen for patients whose tumors have become resistant to checkpoint inhibitors.”

Lower rate of severe adverse events

The chemo-free combination also had the lowest proportion of patients experiencing Grade 3 or higher treatment-emergent adverse events.

These events occurred in 35% of patients receiving roginolisib and dostarlimab, compared with 69% in the triplet group and 75% in the control group.

No fatal adverse events were attributed to roginolisib.

Confirmed partial responses were observed across all three treatment groups. Two patients (12%) responded in the chemo-free group, compared with one patient (6%) in the triplet group and two patients (13%) in the control group.

Clinical benefit lasting at least six months was reported in 24% of patients receiving the chemo-free combination, 31% in the triplet group and 19% in the control group.

The findings indicate that clinical activity was observed across the study, although response rates remained low in this heavily pretreated population.

Overall survival data remain immature

At a data cut-off of September 30, 2026, median follow-up was 6.4 months. Six-month overall survival rates were 74.8% in the chemo-free group, 60.9% in the triplet group and 43.8% in the control group.

However, overall survival data remain immature, and the study was not designed to establish differences in survival between treatment groups. Further follow-up is ongoing.

The results provide early clinical evidence supporting the investigation of PI3Kδ inhibition as a strategy to address immune suppression in patients whose NSCLC has progressed following checkpoint inhibitor treatment.

For iOnctura, the findings also support further investigation of roginolisib in combination with immunotherapy, particularly regimens that could avoid additional chemotherapy.