FDA Grants Tentative Approval to New Cabozantinib Capsule Formulation

The FDA has granted tentative approval to a new capsule formulation of cabozantinib (Omcazio). The product is intended for adult patients with advanced renal cell carcinoma (RCC); adult patients with advanced RCC in combination with nivolumab (Opdivo) as first-line therapy; adult patients with hepatocellular carcinoma (HCC) previously treated with sorafenib (Nexavar); and adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced, or metastatic, well-differentiated extrapancreatic neuroendocrine tumors (epNET).¹

Cabozantinib capsules were developed under the FDA's 505(b)(2) regulatory pathway, which permits an applicant to rely in part on safety and efficacy data from a previously approved product. The new formulation uses an alternate salt of cabozantinib engineered to improve absorption. In bioavailability and bioequivalence studies submitted to the FDA, the capsules were shown to be bioequivalent to the originally approved tablet formulation at a lower milligram dose and to have no clinically significant food effect. The tablet formulation, marketed as Cabometyx, remains commercially available and is unaffected by this action.

Because the formulations are not interchangeable on a milligram-for-milligram basis, the cabozantinib capsule label carries a boxed warning describing the risk of serious adverse reactions or reduced effectiveness from medication errors. The label directs prescribers and pharmacists to confirm the specific cabozantinib product and strength intended before a prescription is written or filled.

A dose-conversion table included in the label maps tablet doses to their bioequivalent capsule doses: a tablet dose of 60 mg once daily corresponds to a capsule dose of 34.5 mg once daily; 40 mg once daily corresponds to 23 mg once daily; and 20 mg once daily corresponds to 11.5 mg once daily.¹

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 cannot yet be marketed in the United States. Handa said it is continuing commercial readiness activities and has not disclosed a timeline for final approval or launch. Bill Liu, chairman and chief executive officer of Handa, called the decision "an important regulatory milestone" for the company and said the formulation was developed to give patients and clinicians additional flexibility pending full approval.

Clinical Rationale

The labeled indications reflect efficacy data generated with the original cabozantinib tablet rather than new trials of the capsule formulation. In the phase 3 METEOR trial (NCT01865747), cabozantinib improved overall survival compared with everolimus in patients with advanced RCC previously treated with a VEGFR tyrosine kinase inhibitor.² The first-line combination of cabozantinib and nivolumab in advanced RCC is based on the phase 3 CheckMate 9ER trial (NCT03141177), which showed longer progression-free and overall survival compared with sunitinib (Sutent).³ The HCC indication stems from the phase 3 CELESTIAL trial (NCT01908426), in which cabozantinib improved overall survival compared with placebo in patients previously treated with sorafenib.⁴ The epNET indication is supported by the phase 3 CABINET trial (NCT03375320), which found that cabozantinib significantly extended progression-free survival compared with placebo in patients with previously treated extrapancreatic and pancreatic neuroendocrine tumors.⁵

Safety and Tolerability

The most common adverse reactions (occurring in ≥20% of patients) with cabozantinib monotherapy are diarrhea, fatigue, palmar-plantar erythrodysesthesia, decreased appetite, hypertension, nausea, vomiting, decreased weight, and constipation. When combined with nivolumab, the most common adverse reactions are diarrhea, fatigue, hepatotoxicity, palmar-plantar erythrodysesthesia, stomatitis, rash, hypertension, hypothyroidism, musculoskeletal pain, decreased appetite, nausea, dysgeusia, abdominal pain, cough, and upper respiratory tract infection.¹ Additional warnings on the label include hemorrhage, gastrointestinal perforation and fistula, thromboembolic events, hypertensive crisis, cardiac failure, osteonecrosis of the jaw, impaired wound healing, reversible posterior leukoencephalopathy syndrome, thyroid dysfunction, and embryo-fetal toxicity; when cabozantinib is combined with nivolumab, hepatotoxicity and adrenal insufficiency require additional monitoring.

REFERENCES

1. Handa Oncology Receives FDA Tentative Approval for OMCAZIO (cabozantinib) Capsules. News release. Handa Oncoloyg. July 31, 2026. Accessed August 3, 2026. https://tinyurl.com/59p5dbvx

2. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016 Jul;17(7):917-927. doi: 10.1016/S1470-2045(16)30107-3.

3. Choueiri TK, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2021 Mar 4;384(9):829-841. doi: 10.1056/NEJMoa2026982.

4. Abou-Alfa GK, Meyer T, Cheng AL, et al. Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma. N Engl J Med. 2018 Jul 5;379(1):54-63. doi: 10.1056/NEJMoa1717002.

5. Chan JA, Geyer S, Zemla T, et al. Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors. N Engl J Med. 2025 Feb 13;392(7):653-665. doi: 10.1056/NEJMoa2403991.