Clinical and biomarker results from a phase II trial of combined cabozantinib and durvalumab in patients with chemotherapy-refractory colorectal cancer (CRC): CAMILLA CRC cohort.

Autor: Saeed A; Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA. saeeda3@upmc.edu.; UPMC Hillman Cancer Center, Pittsburgh, PA, USA. saeeda3@upmc.edu., Park R; Division of Hematology and Medical Oncology, Moffitt Cancer Cente, Tampa, FL, USA., Pathak H; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA., Al-Bzour AN; Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA., Dai J; Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA., Phadnis M; Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA., Al-Rajabi R; Department of Medicine, Division of Medical Oncology, University of Kansas Medical Center, Kansas City, Ks, USA.; University of Kansas Cancer Center, Kansas City, KS, USA., Kasi A; Department of Medicine, Division of Medical Oncology, University of Kansas Medical Center, Kansas City, Ks, USA.; University of Kansas Cancer Center, Kansas City, KS, USA., Baranda J; Department of Medicine, Division of Medical Oncology, University of Kansas Medical Center, Kansas City, Ks, USA.; University of Kansas Cancer Center, Kansas City, KS, USA., Sun W; Department of Medicine, Division of Medical Oncology, University of Kansas Medical Center, Kansas City, Ks, USA.; University of Kansas Cancer Center, Kansas City, KS, USA., Williamson S; Department of Medicine, Division of Medical Oncology, University of Kansas Medical Center, Kansas City, Ks, USA.; University of Kansas Cancer Center, Kansas City, KS, USA., Chiu YC; UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Osmanbeyoglu HU; UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Madan R; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA., Abushukair H; Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA., Mulvaney K; University of Kansas Cancer Center, Kansas City, KS, USA., Godwin AK; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.; University of Kansas Cancer Center, Kansas City, KS, USA.; Kansas Institute for Precision Medicine, University of Kansas Medical Center, Kansas City, KS, USA., Saeed A; Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 20; Vol. 15 (1), pp. 1533. Date of Electronic Publication: 2024 Feb 20.
DOI: 10.1038/s41467-024-45960-2
Abstrakt: CAMILLA is a basket trial (NCT03539822) evaluating cabozantinib plus the ICI durvalumab in chemorefractory gastrointestinal cancer. Herein, are the phase II colorectal cohort results. 29 patients were evaluable. 100% had confirmed pMMR/MSS tumors. Primary endpoint was met with ORR of 27.6% (95% CI 12.7-47.2%). Secondary endpoints of 4-month PFS rate was 44.83% (95% CI 26.5-64.3%); and median OS was 9.1 months (95% CI 5.8-20.2). Grade≥3 TRAE occurred in 39%. In post-hoc analysis of patients with RAS wild type tumors, ORR was 50% and median PFS and OS were 6.3 and 21.5 months respectively. Exploratory spatial transcriptomic profiling of pretreatment tumors showed upregulation of VEGF and MET signaling, increased extracellular matrix activity and preexisting anti-tumor immune responses coexisting with immune suppressive features like T cell migration barriers in responders versus non-responders. Cabozantinib plus durvalumab demonstrated anti-tumor activity, manageable toxicity, and have led to the activation of the phase III STELLAR-303 trial.
(© 2024. The Author(s).)
Databáze: MEDLINE
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