Etude : COSMIC-312 / XL184-312

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Acronyme / Nom
Situation thérapeutique
Cadre réglementaire
Présentation de l'étude
Acronyme / Nom : COSMIC-312 / XL184-312

Situation thérapeutique : Métastatique ou localement avancé

Traitement :

Cadre réglementaire : RIPH1

Dernière MÀJ : 26/02/2020
CIM10 - Localisation(s)
Informations principales
Titre : A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy

Spécialité : Organes digestifs
Localisation : C22 - Tumeur maligne du foie et des voies biliaires intrahépatiques
Informations complémentaires
Schéma : This is a multicenter, randomized, open-label, controlled Phase 3 trial of cabozantinib in combination with atezolizumab versus sorafenib in adults with advanced HCC who have not received previous systemic anticancer therapy in the advanced HCC setting. The primary objective of this study is to evaluate the effect of cabozantinib in combination with atezolizumab on the duration of progression-free survival (PFS) and duration of overall survival (OS) versus sorafenib. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in this patient population.

A pivotal Phase 3 clinical trial testing a combination of Cabometyx (cabozantinib) with Tecentriq (atezolizumab) versus standard care of Nevaxar (sorafenib) in previously untreated patients with advanced hepatocellular carcinoma (HCC) — the most common type of liver cancer — has begun.
The multi-center, randomized study (NCT03755791), sponsored by Exelixis and co-funded by Ipsen, is named COSMIC-312 and aims to include about 640 patients at up to 200 sites worldwide. Patient enrollment is ongoing at study sites in California and Nevada. (More information on study locations and contacts is available here.)
Participants will be assigned randomly to one of three treatment groups: Cabometyx (40 mg once a day) and Genentech’s Tecentriq (1,200 mg every three weeks), Bayer’s Nevaxar (400 mg twice per day), or stand-alone Cabometyx (60 mg once daily). Of note, while both Carbometyx and Nevaxar are delivered as oral tablets, Tecentriq is given intravenously.
The trial’s main goal is to determine if the Cabometyx-Tecentriq combination is better than Nexavar at extending the time patients live without signs of disease progression and extending overall survival. Therapeutic benefit with stand-alone Cabometyx therapy also will be evaluated.
Cabometyx targets receptors commonly expressed by cancer cells, such as MET, AXL, and VEGFR. They are known to be involved in several tumor processes, including new blood vessel formation, as well as tumor cell migration and invasiveness.
In turn, Tecentriq is a type of therapy called immune checkpoint inhibitor, which works by binding to the PD-L1 protein, found in both healthy and cancer cells. The binding of PD-L1 to PD-1 on immune T-cells helps cancer cells evade immune attack. Tecentriq is intended to block this interaction, boosting the immune response.
“Based on past evidence of potential synergistic effects with cabozantinib and immune checkpoint inhibitors, the combination offers promise for patients with advanced liver cancer who have not received prior treatment,” Gisela Schwab, MD, said in a press release. Schwab is Exelixis’ president of product development and medical affairs, and chief medical officer.
“We look forward to learning whether the combination of cabozantinib and atezolizumab may improve outcomes for previously untreated patients,” said R. Kate Kelley, MD, the study’s lead investigator.
Kelly, a professor of clinical medicine at the Division of Hematology/Oncology of University of California San Francisco further said that the more than 800,000 new cases of liver cancer worldwide each year and the poor prognosis for patients with advanced disease mean “there is an urgent need to identify new treatment options.”
Exelixis and Ipsen have an exclusive licensing agreement for the joint commercialization and development of Cabometyx indications outside of the U.S. and Japan. Ipsen will have access to COSMIC-312 results to support potential future regulatory submissions. In the U.S., Cabometyx is being developed and commercialized exclusively by Exelixis, while, in Japan, the company collaborates with Takeda for these purposes.
A decision on whether to approve Cabometyx in the U.S. for previously treated patients with advanced HCC is expected until Jan. 14, following the acceptance of a supplemental new drug application for the therapy by the U.S. Food and Drug Administration.
Cabometyx is approved in the U.S. for the treatment of advanced renal cell carcinoma (RCC). It also is approved in the European Union (EU), Norway, Iceland, Australia, Switzerland, Canada, South Korea, Canada, Brazil and Taiwan for adults with advanced RCC previously on a VEGF-targeted therapy; in the EU for previously untreated intermediate- or poor-risk advanced RCC; and in the EU, Norway, and Iceland for adults with HCC previously treated with Nevaxar.

Phase : III

Stade : Localement avancé à Métastasique

Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : - Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by CT or MRI per the AASLD 2018 or EASL 2018 guidelines.
- The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
- Measurable disease per RECIST 1.1 as determined by the Investigator.
- Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.
- Child-Pugh Score of A.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Critères de non-inclusion : - Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
- Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and immune checkpoint inhibitors (ICIs). Subjects who have received local intratumoral or arterial chemotherapy are eligible; local anticancer therapy must be completed ≥ 28 days before randomization
- Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 8 weeks prior to randomization.
- Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 8 weeks prior to randomization.
- Concomitant anticoagulation with oral anticoagulants
Informations relatives au promoteur
Promoteur :
Type de sponsor : Industriel

Coordonnateur :
Centre investigateur
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Docteur Stéphane CATTAN

Madame Daphnée SORET
03 20 44 59 62 - Poste 30671

Statut de l'essai : CLOS

MAJ : 26/02/2020