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A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma

Trial Status: Closed to Accrual

This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma.

Inclusion Criteria

  • Male or female participants
  • 18 years and older (Japan-20 years and older)
  • Confirmed hepatocellular carcinoma (HCC) based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods.
  • Immunotherapy-naïve
  • Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC.

Exclusion Criteria

  • Prior exposure to immune-mediated therapy
  • Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
  • Gastrointestinal bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
  • Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
  • Main portal vein thrombosis (Vp4) as documented on imaging
  • Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment
  • Active or prior documented autoimmune or inflammatory disease with some exceptions
  • Current or prior use of immunosuppressive medication within 14 days with some exceptions

Arizona

Scottsdale
Mayo Clinic in Arizona
Status: CLOSED_TO_ACCRUAL

California

San Francisco
UCSF Medical Center-Mount Zion
Status: CLOSED_TO_ACCRUAL

Connecticut

New Haven
Yale University
Status: ACTIVE

Florida

Jacksonville
Mayo Clinic in Florida
Status: CLOSED_TO_ACCRUAL
Tampa
Moffitt Cancer Center
Status: ADMINISTRATIVELY_COMPLETE

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: TEMPORARILY_CLOSED_TO_ACCRUAL
Contact: Rachel Lynn Alvey
Phone: 317-278-6455

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE
Massachusetts General Hospital Cancer Center
Status: ACTIVE

New York

New York
Memorial Sloan Kettering Cancer Center
Status: CLOSED_TO_ACCRUAL

North Carolina

Durham
Duke University Medical Center
Status: ACTIVE

Pennsylvania

Philadelphia
Fox Chase Cancer Center
Status: CLOSED_TO_ACCRUAL
Thomas Jefferson University Hospital
Status: COMPLETED

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: CLOSED_TO_ACCRUAL

Singapore

Singapore
Johns Hopkins Singapore
Status: CLOSED_TO_ACCRUAL
Contact: Akhil Chopra
Phone: 65-68802171

The study will comprise of 6 parts. Participants in Part 1A (safety run-in cohort), Part 1B

(efficacy-gating cohort), Part 2A, and Part 4 will receive weight-based dosing regimens; and

participants in Part 2B and Part 3 will receive fixed dosing regimens. Part 1A Stage 2 of the

study may start after the first 3 participants in Stage 1 have been observed on study for at

least 4 weeks. In addition, a separate cohort of participants will be enrolled in mainland

China (China cohort) once global recruitment in Part 2A will be closed.

- In Part 1 (both 1A and 1B), participants will receive tremelimumab 1 mg/kg intravenous

(IV) every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W.

- In Part 2A, participants will be randomized in a 1:1:1 ratio to receive:

- Durvalumab 20 mg/kg Q4W

- Tremelimumab 10 mg/kg Q4W × 7 doses followed by every 12 weeks (Q12W)

- Tremelimumab 1 mg/kg Q4W × 4 doses + durvalumab 20 mg/kg Q4W, followed by

durvalumab 20 mg/kg Q4W

- In China cohort, Part 2A study design will be followed.

- In Part 2B, participants will receive tremelimumab 300 mg × 1 dose + durvalumab 1500 mg

Q4W.

- In Part 3, participants will be randomized in a 2:2:1:2 ratio to receive:

- Durvalumab 1500 mg Q4W

- Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W

- Tremelimumab 750 mg Q4W for 7 doses followed by Q12W

- Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W, followed by durvalumab

1500 mg Q4W.

Following protocol amendment 5, enrollment into 'Tremelimumab 75 mg Q4W × 4 doses +

durvalumab 1500 mg' arm will close. Participants will be randomized at a ratio of 2:1:2 in

'Durvalumab 1500 mg Q4W', 'Tremelimumab 750 mg Q4W for 7 doses followed by Q12W', and

'Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W' arms, respectively.

• In Part 4, participants will receive durvalumab 1120 mg (15 mg/kg) + bevacizumab 15 mg/kg

every 3 weeks (Q3W).

Participants will receive the treatment until confirm progressive disease, withdrawal of

consent, lost to follow-up, or development of other reason for treatment discontinuation,

whichever occurs first.

All participants will be followed for survival until the end of study visit (last participant

discontinues the study treatment).

Trial Phase Phase II

Trial Type Treatment

Lead Organization
MedImmune Inc

  • Primary ID D4190C00022
  • Secondary IDs NCI-2016-00207
  • Clinicaltrials.gov ID NCT02519348