FDA greenlights trial of orellanine in metastatic renal cell carcinoma

The FDA has accepted an investigational new drug (IND) application to launch the phase 1/2 Oncorella-1 trial (NCT05287945) in the US, Oncorena announced in a news release.¹

The study will evaluate the investigational drug product ONC175 (orellanine) in patients with metastatic clear cell or papillary renal cell carcinoma (RCC) who have exhausted other options.

The Oncorella-1 trial was first launched in Stockholm, Sweden.

"This approval brings us closer to being able to evaluate the potential for this novel treatment in patients in desperate need for new and better options,” said Börje Haraldsson, CEO and co-founder of Oncorena, in the news release.¹ “We are excited to start the first US site, MD Anderson in Houston, Texas, where the study will be led by investigator Professor Nizar Tannir, a world-leading expert in renal cancer."

The Oncorella-1 trial was first launched at the Karolinska University Hospital in Stockholm, Sweden, with the dosing of the first patient announced in September 2023.² With sites in both Sweden and the US, the trial plans to enroll up to 75 adult patients with metastatic clear cell or papillary RCC who are on dialysis due to kidney failure.

To be eligible for enrollment, patients must have histologically confirmed advanced clear cell or papillary RCC, an ECOG performance status of 0-2, acceptable hematologic laboratory values, and a life expectancy of at least 3 months, among other criteria.³

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 intravenous infusion of ONC175 for 30 minutes. 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 preliminary anti-tumor effects of ONC175 will be assessed.

The 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 level for phase 2 of the study. The study will also assess changes in arterial blood pressure measurements, changes in pulse rate measurements, changes in respiratory rate measurements, changes in temperature measurements, and changes in physical examination findings.

About ONC175

According to Oncorena,¹ ONC175 is being developed “as a potential curative treatment of metastatic renal cell carcinoma in patients with no remaining kidney function.” The drug’s active component is synthetically produced orellanine, which is found in mushrooms belonging to the Cortinarius family.

In preclinical studies⁴ orellanine demonstrated the ability to target primary and metastatic clear-cell RCC in vitro and in vivo and demonstrated potent anti-tumor effects. Treatment with orellanine did not lead to off-target toxicity.

The authors concluded, “In nude rats carrying human ccRCC xenografts, brief orellanine treatment eliminated more than 90% of viable tumor mass compared to control rats. This identifies orellanine as a potential treatment concept for ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC.”

REFERENCES

1. Oncorena receives FDA approval to initiate studies in the US. News release. Oncorena. Published online and accessed March 18, 2025. https://www.prnewswire.com/news-releases/oncorena-receives-fda-approval-to-initiate-studies-in-the-us-302404183.html

2. 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 March 18, 2025. 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

3. Study of orellanine in metastatic clear-cell or papillary renal cell carcinoma. ClinicalTrials.gov. Last updated June 24, 2024. Accessed March 18, 2025. https://clinicaltrials.gov/study/NCT05287945

4. Buvall L, Hedman H, Khramova A, et al. Orellanine specifically targets renal clear cell carcinoma. Oncotarget. 2017;8(53):91085-91098. doi:10.18632/oncotarget.19555