Roginolisib, a first-in-class small molecule allosteric modulator of PI3Kδ, has been given the green light by the FDA to continue studies for patients with solid and hematologic malignancies.
The FDA has granted permission to proceed with clinical investigations of roginolisib in the United States, according to iOnctura.1
Roginolisib is currently being developed for patients with solid and hematologic malignancies, including uveal melanoma. Roginolisib is the first novel allosteric modulator of PI3K and utilizes a unique binding mode that when combined with high selectivity for PI3K. It is expected to improve safety and tolerability relative to that of earlier generation inhibitors.
"As we remain on track to deliver final clinical data from the initial patients treated with roginolisib in 2024, the clearance of our [investigational new drug] application demonstrates our commitment to driving roginolisib through the clinic" said Catherine Pickering, chief executive officer of iOnctura, in a press release.
The phase 1 DIONE-01 trial is actively investigating roginolisib in patients with metastatic cancers. The 2-part, first-in-human study is fully enrolled and includes patients ≥18 years of age who have an ECOG performance status of 0 to 1.2The extension phase of the DIONE-01 trial is ongoing and evaluating the agent in patients with advanced cancers and as a combination partner for conventional and immunotherapies.
Patients with non-Hodgkin lymphoma with an ECOG performance status of 2 also were allowed to enroll. Additional eligibility requirements including histologically or cytologically confirmed advanced or metastatic malignancies and measurable disease per RECIST v.1.1 or mRECIST.
Among the patients enrolled and treated in the study to date, roginolisib monotherapy led to 7% grade 3/4 toxicities, and no dose-limiting toxicities have been observed.1 Additionally, there have been no drug-related serious adverse events (AE) or drug-related AEs that have led to dose interruptions or discontinuation of treatment.
For a secondary end point of overall survival, rates have not been reached, and 62% of patients were alive at 12 months. These data compare favorably to historical controls of 34% in the same setting.
Moreover, the long-term administration of roginolisib has shown to be well-tolerated. In the study, patients have been treated for up to 40 months and clinical activity appears promising in patients with both solid and hematological cancers.
Final data from the study are expected to be released in Q1 of 2024.
"We believe roginolisib has the potential to slow or halt the progression of uveal melanoma, so providing an important treatment option for patients who currently have no approved therapeutic options after they progress on their first line therapy," added Pickering in a press release.