Salt-Formulation Cabozantinib Capsules Receive FDA Tentative Approval in RCC, HCC, epNET

The FDA has granted tentative approval to cabozantinib (Omcazio) capsules, a novel 505(b)(2) alternate-salt formulation of cabozantinib, for patients across various cancer indications, according to a news release from Handa Pharmaceuticals.¹

Omcazio is indicated for adult patients with advanced renal cell carcinoma (RCC), both as a single agent and in combination with nivolumab (Opdivo) in the first-line setting; adult patients with hepatocellular carcinoma (HCC) previously treated with sorafenib (Nexavar); and adult and pediatric patients 12 years and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic neuroendocrine tumors (epNETs).

“Tentative approval marks an important regulatory milestone for Handa [Phamraceuticals]. We developed Omcazio with the goal of providing an alternative oral cabozantinib formulation that may offer greater flexibility for patients and health care providers,” stated Bill Liu, chairman and chief executive officer of Handa, in the press release.¹ “We are continuing our commercial readiness activities and look forward to making Omcazio available to patients following FDA final approval.”

What is Omcazio and how does it differ from other cabozantinib formulations?

Omcazio is an alternate-salt capsule formulation of cabozantinib, a tyrosine kinase inhibitor, developed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. In bioavailability and bioequivalence studies, Omcazio demonstrated bioequivalence to Cabometyx, a previously approved formulation of cabozantinib, at a lower milligram dose, along with improved absorption of cabozantinib and no clinically significant food effect.² Meaningfully, Omcazio capsules can be administered with or without food.

What are the approved indications for Omcazio?

Beyond single-agent and nivolumab-combination use in advanced RCC, Omcazio covers patients with HCC who progressed on prior sorafenib and both adult and adolescent patients with previously treated epNETs.

How does Omcazio’s dosing compare with Cabometyx?

Because Omcazio is bioequivalent to Cabometyx at a lower dose, the approved label includes specific conversion guidance for patients switching between the 2 products: a 60 mg once-daily Cabometyx dose corresponds to 34.5 mg once daily of Omvazio, 40 mg corresponds to 23 mg, and 20 mg corresponds to 11.5 mg. The label carries a boxed warning noting that Omcazio is not substitutable on a milligram-to-milligram basis with other cabozantinib products, and that inappropriate substitution or incorrect conversion can increase the risk of serious adverse reactions.

What are the safety considerations for Omcazio?

The most common adverse reactions, occurred in 20% or more of patients, with single-agent Omcazio include diarrhea, fatigue, palmar-plantar erythrodysesthesia, decreased appetite, hypertension, nausea, vomiting, decreased weight, and constipation. When used in combination with nivolumab, additional common reactions include hepatotoxicity, stomatitis, rash, hypothyroidism, musculoskeletal pain, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.

Prescribing information warns of hemorrhage, gastrointestinal perforations and fistulas, thromboembolic events, cardiac failure, osteonecrosis of the jaw, impaired wound healing, reversible posterior leukoencephalopathy syndrome, thyroid dysfunction, and embryo-fetal toxicity.

Drug interactions were featured. When coadministration of Omcazio with “strong” CYP3A inhibitors cannot be avoided, Omcazio dose should be reduced. For strong or moderate CYP3A inhibitors, the dosage of Omcazio should be increased if coadministration cannot be avoided. There are no contraindications to Omcazio.

Patients are advised not to breastfeed when receiving Omcazio. Pediatric patients receiving Omcazio should have their growth plates monitored and interruption or discontinuation is recommended if abnormalities occur.

What is the regulatory status and next steps for OMCAZIO?

A tentative approval indicates that the FDA has determined an application meets the agency’s standards for safety, effectiveness, and manufacturing quality, but the product is not yet available for commercial distribution in the US.

References

1. Handa Oncology receives FDA tentative approval for OMCAZIO (cabozantinib) capsules. News release. Handa Pharmaceuticals, Inc. July 31, 2026. Accessed August 3, 2026. https://tinyurl.com/4pc9a749
2. CABOMETYX (cabozantinib) tablets, prescribing information. Exelixis, Inc. Accessed August 3, 2026. https://tinyurl.com/3keuuepm