The phase 1/2 Oncorella-1 trial is expected to enroll up to 40 patients with advanced kidney cancer who are on dialysis due to renal failure.
The first patient has been treated in the phase 1/2 Oncorella-1 trial (NCT05287945) exploring ONC175 (orellanine) in patients with advanced clear-cell or papillary renal cell carcinoma (RCC) who are on dialysis due to renal failure, announced Oncorena, the developer of the treatment, in a news release.1
The first patient underwent infusion with ONC175 for 30 minutes at the Center of Clinical Cancer studies at Karolinska University Hospital in Stockholm, Sweden. No complications were reported.
"I am happy to announce first patient, first treatment in our clinical phase 1/2 trial, Oncorella-1, with ONC175 (orellanine). This is a milestone for Oncorena accelerating our development plan since these patients are in need of more effective therapies," Börje Haraldsson, the CEO and CSO of Oncorena AB, said in a news release.1
In total, the Oncorella-1 trial will include up to 40 adult patients with metastatic clear-cell or papillary RCC. Patients will be excluded from the study if they have a diagnosis of any other malignancy within 2 years of enrollment, have symptomatic brain metastases, received radiotherapy or systemic anti-cancer therapy within 4 weeks prior to the first dose, have not recovered from adverse events (AEs) from prior anti-cancer medications, have received any other investigational product within 4 weeks before the first dose, are pregnant or breastfeeding, or have an uncontrolled medical condition.2
The study will be conducted in 2 phases consisting of an intra-patient dose escalation phase followed by a dose expansion phase. Participants will receive .05-4.9 mg/kg single intravenous administration of ONC175 for 30 minutes following hemodialysis.
All patients included in the study will be monitored by an Independent Data Review Committee for 4 weeks following infusion. The safety, tolerability, pharmacokinetics, and anti-tumor effects of ONC175 will be assessed. Primary outcome measures include the occurrence of dose-limiting toxicities or AEs, determination of a maximum tolerated dose, and the determination of a recommended dose for phase 2 of the study.
According to the news release,1 ONC175 is a “being developed for organ-specific chemotherapy with curative potential for patients with metastatic renal cancer.” The synthetic drug’s main component is orellanine, which is found in mushrooms belonging to the Cortinarius family.
Preclinical studies3 showed that orellanine could target metastatic clear-cell RCC in vitro and in vivo and demonstrated potent anti-tumor effects.
Jeffrey Yachnin, MD, the study’s principal investigator, added about ONC175,1 "It concerns a very different and unique medicine that is being tested here on patients with disseminated kidney cancer. We are very happy that the study is underway and we look forward to the results.”
Additional patients in the Oncorella-1 study are expected to undergo treatment this fall.
1. Oncorena’s first patient treated with ONC175 (orellanine) in clinical phase I/II trial in patients with metastatic renal cancer and dialysis at Karolinska University Hospital in Stockholm, Sweden. News release. Oncorena AB. September 4, 2023. Accessed September 5, 2023. https://www.prnewswire.com/news-releases/oncorenas-first-patient-treated-with-onc175-orellanine-in-clinical-phase-iii-trial-in-patients-with-metastatic-renal-cancer-and-dialysis-at-karolinska-university-hospital-in-stockholm-sweden-301916755.html
2. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Study of orellanine in metastatic clear-cell or papillary renal cell carcinoma. Last updated August 14, 2023. Accessed September 5, 2023. https://clinicaltrials.gov/study/NCT05287945
3. Buvall L, Hedman H, Khramova A, et al. Orellanine specifically targets renal clear cell carcinoma. Oncotarget. Accessed September 5, 2023. 2017;8(53):91085-91098. doi:10.18632/oncotarget.19555