Risovalisib Is Approved in Japan for Recurrent Ovarian Clear Cell Carcinoma

The Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the PI3Kα inhibitor risovalisib (risovalisib mesilate hydrate) for the treatment of patients with advanced or recurrent ovarian clear cell carcinoma harboring PIK3CA gene mutations following progression on chemotherapy.¹

The regulatory agency also approved the AmoyDx PIK3CA Mutation Detection Kit for use as a companion diagnostic to determine whether patients with ovarian clear cell carcinoma may be eligible for targeted treatment with risovalisib based on the presence or absence of PIK3CA gene mutations.²

The approval of risovalisib was supported by findings from the phase 2 CYH33-G201 trial (NCT05043922). This approval follows the June 30, 2025, orphan drug designation for risovalisib in this indication.³ Overall, data from clinical trials investigating risovalisib have shown that the agent is effective and has a manageable safety profile across advanced solid tumors harboring PIK3CA mutations, including ovarian, breast, and endometrial cancers.

What was the design of the CYH33-G201 trial evaluating risovalisib in ovarian clear cell carcinoma?

This open-label, multicenter trial enrolled female patients at least 18 years of age with histologically or cytologically confirmed recurrent or persistent ovarian, fallopian tube, or peritoneum clear cell carcinoma with identified PIK3CA mutation status whose disease had progressed on prior standard chemotherapy.⁴ Patients needed to have an ECOG performance status of 0 or 1, as well as adequate bone marrow and organ function within 28 days of screening.

Patients were ineligible to enroll if they had received prior treatment with any PI3K, mTOR, or AKT inhibitor; had undergone radical radiation therapy within 4 weeks before the first dose of risovalisib or local palliative radiation therapy for bone metastases within 2 weeks prior to dosing; or had unresolved toxicities from prior treatment. They were also excluded if they had received hematopoietic colony-stimulating growth factors within 2 weeks before dosing; had symptomatic central nervous system metastases; or had undergone major surgery or experienced significant traumatic injury within 28 days before the first dose of risovalisib or had not recovered from associated major adverse effects (AEs).

Additional exclusion criteria included known HIV infection with a history of acquired immunodeficiency syndrome–defining opportunistic infection within 12 months prior to study treatment; active hepatitis B or hepatitis C infection; a history of acute pancreatitis within 1 year of screening or chronic pancreatitis; or clinically significant cardiovascular disease.

Patients received risovalisib at 40 mg daily.

Overall response rate per RECIST 1.1 criteria in patients with PIK3CA mutations served as the trial’s primary end point. Secondary end points included progression-free survival by blinded, independent review committee per RECIST 1.1 criteria, overall survival in each PIK3CA mutation status cohort, and the identification of genetic and protein biomarker alterations that could affect the PI3K signaling pathway. Other end points included safety and tolerability, defined as the type, incidence, duration, severity and seriousness of AEs; the number and proportion of Japanese patients who experienced a dose-limiting toxicity during the first 28 days of treatment in the safety run-in portion of the study; and pharmacokinetic parameters, defined as the peak plasma concentration and the area under the plasma concentration–vs-time curve.

How is the AmoyDx PIK3CA Mutation Detection Kit used?

TheAmoyDx PIK3CA Mutation Detection Kit detects PIK3CA gene mutations in DNA extracted from FFPE tumor tissue that has confirmed presence of tumor cells.² Tissue samples are tested using real-time PCR. Notably, the test has a shelf life of 12 months.

References

1. PI3Kα inhibitor “Heitzexin 10 mg tablets” after cancer chemotherapy for ovarian clear cell carcinoma with advanced PIK3CA gene mutations obtained manufacturing and sales approval. News release. Haihe Pharmaceutical Co, Ltd. March 23, 2026. Accessed March 27, 2026. https://kk.haihepharma.com/news/news_20260313001.html?fbclid=IwdGRleAQt7r9leHRuA2FlbQIxMQBzcnRjBmFwcF9pZAo2NjI4NTY4Mzc5AAEe-BF6ZHFqDJ_PRFmNBt6An_EHpfGuhzDQnA5m7IhvLFA97IyRdQxkMCCKzMY_aem_Io8EyNDgM_EcC3KqR2sRXw
2. AmoyDx PIK3CA Mutation Detection Kit approved as a companion diagnostic for risovalisib in Japan. News release. Amoy Diagnostics Co, Ltd. March 23, 2026. Accessed March 27, 2026. https://www.amoydiagnostics.com/about/press-releases/281
3. HaiHe Biopharma’s selective PI3Kα inhibitor was granted orphan drug designation in Japan. News release. June 30, 2025. Accessed March 27, 2026. https://www.haihepharma.com/en/news/details/434
4. A study to evaluate the efficacy and safety of CYH33 in patients with recurrent/​persistent ovary clear cell carcinoma. ClinicalTrials.gov. Updated January 30, 2026. Accessed March 27, 2026. https://clinicaltrials.gov/study/NCT05043922