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Clinical Trial
. 2025 Nov 14;31(22):4655-4663.
doi: 10.1158/1078-0432.CCR-25-2143.

Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial (CABATEN/GETNE-T1914)

Jaume Capdevila  1 , Jorge Hernando  1 , Javier Molina-Cerrillo  2 , Marta Benavent Viñuales  3 , Rocio Garcia-Carbonero  4 , Alex Teulé  5 , Ana Custodio  6 , Paula Jimenez-Fonseca  7 , Carlos López  8 , Cinta Hierro  9 , Alberto Carmona-Bayonas  10 , Vicente Alonso  11 , Marta Llanos  12 , Isabel Sevilla  13 , Alejandro García-Álvarez  1 , Teresa Alonso-Gordoa  2 , Inmaculada Gallego Jiménez  3 , Beatriz Antón-Pascual  2 , Andrea Modrego Sánchez  4 , Enrique Grande  14
Affiliations
Clinical Trial

Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial (CABATEN/GETNE-T1914)

Jaume Capdevila et al. Clin Cancer Res. .

Abstract

Purpose: Multikinase inhibitors have shown efficacy in endocrine neoplasms, and synergism with immune checkpoint inhibitors has been noted in other tumors.

Patients and methods: This is a prospective, multicenter, open-label, Simon two-stage optimal design, phase II study including patients with advanced and refractory endocrine and neuroendocrine neoplasms in six cohorts: lung well-differentiated neuroendocrine tumors, anaplastic thyroid cancer (ATC), adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PPGL), well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET), and grade 3 extrapulmonary neuroendocrine neoplasms. Patients received atezolizumab 1,200 mg intravenously every 3 weeks plus cabozantinib 40 mg/day orally until disease progression or unacceptable toxicity. The primary objective was the overall response rate (ORR) by RECIST 1.1.

Results: From October 2020 to December 2022, 93 patients were included. The ORR was 14.3% [95% confidence interval (CI), 1.8-42.8] in ATC (N = 14); 8.3% (95% CI, 1.0-27.0) in ACC (N = 24); 15.4% (95% CI, 1.9-45.5) in PPGL (N = 13), and 16.7% (95% CI, 4.7-37.4) in GEP-NET (N = 24). Lung well-differentiated neuroendocrine tumors and grade 3 extrapulmonary neuroendocrine neoplasms had no responses. The duration of response was 20.4 months in ATC, 13.1 months in ACC, 12.2 months in PPGL, and 15.8 months in GEP-NET. Survival rates at 12 months in ATC and ACC were 47.6% and 47.6%, respectively. No unexpected toxicity was observed.

Conclusions: Cabozantinib and atezolizumab were safely administered and showed promising ORR, and preliminary long-term survival rates were observed in aggressive and pretreated ACC and ATC, which warrants further investigation.

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Conflict of interest statement

J. Capdevila reports grants from Ipsen and Roche during the conduct of the study; grants and personal fees from Ipsen, Exelixis, Eisai, and ITM Radiopharma; personal fees from Bayer, Eli Lilly and Company, Novartis, Incyte Corporation, Sanofi, Merck, Esteve, Pfizer, and Advanz; and grants from AstraZeneca and Gilead Sciences outside the submitted work. J. Molina-Cerrillo reports grants from Ipsen and Roche during the conduct of the study; grants, personal fees, and nonfinancial support from MSD; personal fees and nonfinancial support from Astellas Pharma, Adium Pharma, and Bristol Myers Squibb; personal fees from AAA Pharma and Pfizer; and grants from Exelisis and Recordati outside the submitted work. M. Benavent Viñuales reports other support from Pfizer, Ipsen, Gilead Sciences, Esteve, and Novartis outside the submitted work. R. Garcia-Carbonero reports personal fees from Ipsen during the conduct of the study, as well as personal fees from Advanz Pharma, Astellas Pharma, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Crinetics, Esteve, GSK, Hutchmed, ITM Radiopharma, MSD, Novartis, Novocure, PharmaMar, Pierre Fabre, Sanofi, Servier, and Takeda outside the submitted work. A. Teulé reports other support from Advanced Accelerator Applications (ADACAP), Novartis, Esteve, Ipsen, Advanz Pharma, and AstraZeneca outside the submitted work. C. López reports grants, personal fees, and nonfinancial support from Ipsen, Eisai, and Roche; personal fees and nonfinancial support from Novartis/AAA Pharma; and grants from Pfizer during the conduct of the study. C. Hierro reports other support from Eli Lilly and Company, AstraZeneca, Bristol Myers Squibb, MSD, Jazz Pharmaceuticals, ALX Oncology, Amgen, and Roche and grants from Merck outside the submitted work. I. Sevilla reports grants from GETNE during the conduct of the study, as well as personal fees from Ipsen, AAA Pharma, Novartsi, PharmaMar, Esteve, Merck, Deciphera, and Boehringer Ingelheim outside the submitted work. A. García-Álvarez reports other support from Ipsen, personal fees and other support from Novartis, Elli Lilly and Company, and Eisai, and other support from Amgen and Advanz Pharma outside the submitted work. T. Alonso-Gordoa reports personal fees from Bayer, Astellas Pharma, Pfizer, Bristol Myers Squibb, MSD, Adacap, Novartis, Eisai, and Eli Lilly and Company; grants and personal fees from Johnson & Johnson; and personal fees and nonfinancial support from Ipsen during the conduct of the study. B. Antón-Pascual reports grants from NET España and personal fees from AAA Pharma, Novartis, Advanz Pharma, Merck, MSD, Persan Farma, Nutricia, and Servier outside the submitted work. E. Grande reports grants from Roche and Ipsen during the conduct of the study, as well as grants from Merck, Astellas Pharma, AstraZeneca, Novartis, and Merck outside the submitted work. No disclosures were reported by the other authors.

Figures

Figure 1.
Figure 1.
Patient distribution and treatment compliance by cohort. Screening failure, criteria met for advancing from the first to the second stage [based on responses to atezolizumab 1,200 mg intravenously (IV) every 3 weeks plus cabozantinib 40 mg/day orally], and reasons for treatment discontinuations are depicted. C, cabozantinib; A, atezolizumab; TKI, tyrosine kinase inhibitor.
Figure 2.
Figure 2.
ORR for each cohort: lungNET, ATC, ACC, PPGL, G1–2 GEP-NET, and G3 EP-NEN. CPS, combined positive score; MSI, microsatellite instability; MSS, microsatellite-stable; NA, not available; PR, partial response; TMB, tumor mutational burden. Molecular analyses were performed in the 10 patients who responded to treatment.
Figure 3.
Figure 3.
Survival endpoints. PFS for each cohort (A). OS for each cohort (B). m, month.
Figure 4.
Figure 4.
Safety analysis and treatment compliance for atezolizumab and cabozantinib. Most frequent toxicities at a ≥5% threshold for any grade or grade ≥3. The frequency of patients is indicated as a percentage. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BLS, blood and lymphatic system; CPK, creatine phosphokinase; PPE, palmar–plantar erythrodysesthesia; SST, skin and subcutaneous tissue.
See this image and copyright information in PMC

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