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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Exelixis Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 May 2019 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Exelixis, Inc.

External identifiers

EU CT number

2024-516479-34-00

EudraCT number

2018-003354-24

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Safety, Pharmacokinetic, Pharmacogenomic, Therapy, Efficacy

The primary objective of this study is to evaluate the efficacy of cabozantinib in combination with atezolizumab versus sorafenib in subjects with advanced HCC who have not received previous systemic anticancer therapy.

Secondary objectives 1

1. The secondary objective is to evaluate the activity of single-agent cabozantinib compared with sorafenib in subjects with advanced HCC who have not received previous systemic anticancer therapy.

Conditions and MedDRA coding

Hepatocellular carcinoma

Regulatory references

Scientific advice from competent authorities

Medicines Evaluation Board, Norwegian Medical Products Agency, Swedish Medical Products Agency, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histological or cytological diagnosis of HCC or clinical diagnosis of HCC in cirrhotic patients by multiphase imaging using CT or MRI per the American Association for the Study of Liver Diseases (AASLD) guidelines or European Association for the Study of the Liver (EASL 2018)
2. The subject has disease that is not amenable to a curative treatment approach (eg, transplant, surgery, ablation therapy) or locoregional therapy (eg, TACE).
3. Measurable disease per RECIST 1.1 as determined by the Investigator. Barcelona Clinic Liver Cancer (BCLC) stage Category B or C.
4. Child-Pugh Score of A.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria 5

1. Known fibrolamellar carcinoma, sarcomatoid HCC or mixed hepatocellular cholangiocarcinoma.
2. Prior systemic anticancer therapy for advanced HCC including but not limited to chemotherapy, small molecule kinase inhibitors, and ICIs. Subjects who have received local intratumoral or arterial chemotherapy are eligible. Subjects who have received any local anticancer therapy within 28 days prior to randomization are ineligible
3. Radiation therapy for bone metastasis within 2 weeks, any other external beam radiation therapy within 8 weeks prior to randomization.
4. 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.
5. Concomitant anticoagulation with oral anticoagulants.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Duration of Progression Free Survival (PFS) per RECIST 1.1, by Blinded Independent Radiology Committee (BIRC) for the experimental arm (cabozantinib+atezolizumab) vs the control arm ( sorafenib)
2. Duration of Overall Survival (OS) for the experimental arm (cabozantinib+atezolizumab) vs the control arm (sorafenib)

Secondary endpoints 1

1. PFS per RECIST 1.1 by BIRC for the single-agent cabozantinib arm vs the control arm (sorafenib)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Exelixis Inc.

Sponsor organisation

Exelixis Inc.

Address

1851 Harbor Bay Parkway

City

Alameda

Postcode

94502-3010

Country

United States

Scientific contact point

Organisation

Exelixis Inc.

Contact name

Exelixis, Inc.

Public contact point

Organisation

Exelixis Inc.

Contact name

Exelixis, Inc.

Third parties 1

Locations

5 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications