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.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
20 Feb 2024
Historique:
received: 17 10 2023
accepted: 31 01 2024
medline: 21 2 2024
pubmed: 21 2 2024
entrez: 20 2 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 38378868
doi: 10.1038/s41467-024-45960-2
pii: 10.1038/s41467-024-45960-2
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1533

Informations de copyright

© 2024. The Author(s).

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Auteurs

Anwaar 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.

Robin Park (R)

Division of Hematology and Medical Oncology, Moffitt Cancer Cente, Tampa, FL, USA.

Harsh Pathak (H)

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Ayah Nedal Al-Bzour (AN)

Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA.

Junqiang Dai (J)

Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.

Milind Phadnis (M)

Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.

Raed 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.

Anup 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.

Joaquina 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.

Weijing 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.

Stephen 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.

Yu-Chiao Chiu (YC)

UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

Hatice Ulku Osmanbeyoglu (HU)

UPMC Hillman Cancer Center, Pittsburgh, PA, USA.

Rashna Madan (R)

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS, USA.

Hassan Abushukair (H)

Department of Medicine, Division of Hematology & Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, USA.

Kelly Mulvaney (K)

University of Kansas Cancer Center, Kansas City, KS, USA.

Andrew K 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.

Azhar Saeed (A)

Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT, USA.

Classifications MeSH