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Clinical Trial
. 2025 Feb 18;110(3):830-837.
doi: 10.1210/clinem/dgae512.

Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer

Bhavana Konda  1 , Eric J Sherman  2 , Erminia Massarelli  3 , Jorge Nieva  4 , Jameel Muzaffar  5 , John C Morris 3rd  6 , Mabel Ryder  6 , Alan L Ho  2 , Mark Agulnik  3 , Lai Wei  7 , Demond Handley  7 , Catherine Moses  1 , Rajani Jacob  1 , John Wright  8 , Howard Streicher  8 , William Carson  9 , Manisha H Shah  1
Affiliations
Clinical Trial

Cabozantinib Plus Ipilimumab/Nivolumab in Patients With Previously Treated Advanced Differentiated Thyroid Cancer

Bhavana Konda et al. J Clin Endocrinol Metab. .

Erratum in

Abstract

Background: This investigator-initiated phase II trial aimed to evaluate the efficacy of cabozantinib in combination with nivolumab and ipilimumab (CaboNivoIpi) in previously treated patients with radioactive iodine-refractory differentiated thyroid cancer.

Methods: Eligible patients with radioactive iodine-refractory differentiated thyroid cancer who progressed on 1 prior line of vascular endothelial growth factor receptor-targeted therapy received a 2-week run-in of cabozantinib monotherapy followed by CaboNivoIpi for 4 cycles (cycle length = 6 weeks), followed by cabozantinib plus nivolumab (cycle length = 4 weeks) until disease progression. The primary endpoint was objective response rate (ORR) within the first 6 months of treatment. A Simon optimal 2-stage design allowed for an interim analysis after accrual of 10 evaluable patients. At least 5 responses were needed to proceed to stage 2.

Results: Among 11 patients enrolled, the median age was 69 years. Prior vascular endothelial growth factor receptor-targeted therapies included lenvatinib, pazopanib, and sorafenib plus everolimus. Median follow-up was 7.9 months. Among 10 evaluable patients, ORR within the first 6 months of treatment was 10% (1 partial response). Median progression-free survival was 9 months (95% CI, 3.0-not reached) and median overall survival was 19.2 months (95% CI, 4.6-not reached). Grade 3/4 treatment-related adverse events (AEs) were noted in 55% (6/11) and grade 5 AEs in 18% (2/11) of patients. The most common treatment-related AE was hypertension. The study did not reach its prespecified efficacy threshold.

Conclusion: CaboNivoIpi had low ORRs and a high rate of grade ≥3 treatment-related AEs.

Clinical trial registration: NCT03914300.

Keywords: VEGFR; cabozantinib; differentiated thyroid cancer; immune checkpoint inhibitors; ipilimumab; nivolumab.

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Figures

Figure 1.
Figure 1.
Waterfall plot showing treatment responses with CaboNivoIpi. The lower horizontal line represents the RECIST v1.1 threshold for partial response (30% decrease in the sum of target lesion diameters). Abbreviated study IDs from left to right: #4, 14, 11, 1, 9, 6, 8, 13, 5, 12.
Figure 2.
Figure 2.
Swimmer's plot for all 11 patients who received study treatment. Each bar represents a patient; the time on study treatment is represented by the solid bar. For those subjects who came off study for reasons other than disease progression, the reasons are stated next to the bar: PD = progressive disease, PR = partial response, SD = stable disease per RECIST v1.1. Abbreviated study IDs from top to bottom: #5, 12, 9, 14, 1, 8, 13, 4, 6, 11, 15.
Figure 3.
Figure 3.
Median progression-free survival.
Figure 4.
Figure 4.
Median overall survival.
See this image and copyright information in PMC

References

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