UCDCRC/19/01

University College Dublin

Catherine McAuley Centre, Nelson Street, Dublin 7, Ireland, D07 A8NN

Gráinne O'Reilly, Director of Research Clinical Trials, University College Dublin, +353 17166603, grainne.oreilly1@ucd.ie

Gráinne O'Reilly, Director of Research Clinical Trials, University College Dublin, +353 17166603, grainne.oreilly1@ucd.ie

No

No

No

Final

07 Sep 2023

Yes

12 Dec 2022

Yes

12 Dec 2022

No

To preliminarily evaluate the 6-month progression free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced HCC (in combination with TACE). The trial protocol is derived from a US-based trial (with ClinicalTrials.gov id number 16-C-0135) sponsored by the NIH. A combined analysis will be undertaken but results from the Irish cohort only are reported here.

The clinical research team (chief investigator, clinical trial nurse, research registrar, co- investigators) will meet on a regular (at least monthly) basis during the accrual and active treatment phase of the study to review eligibility of prospective participants and review safety data of patients and discuss each patient already enrolled. Decisions about dose level enrollment and dose escalation if applicable will be made based on the toxicity data from prior patients. All data will be collected in a timely manner and reviewed by the principal investigator or a lead associate investigator. Adverse events will be reported as required above. Any safety concerns, new information that might affect either the ethical and or scientific conduct of the trial, or protocol deviations will be immediately reported to the IRB, the Sponsor and the manufacturer. The principal investigator will review adverse event and response data on each patient to ensure safety and data accuracy. The principal investigator will personally conduct or supervise the investigation and provide appropriate delegation of responsibilities to other members of the research staff.

31 Oct 2019

No

No

Ireland: 13

13

13

0

0

0

0

0

0

0

13

0

Single period (overall period)

Not applicable

This is a single arm, open-label study.

Yes

Tremelimumab

Solution for infusion

Infusion

Tremelimumab 300mg for 1 dose. Tremelimumab is to be administered as an IV solution of 10 mg/kg at a rate of 250 mL/hr, followed by observation for 60 minutes.

Durvalumab

Solution for infusion

Infusion

Dose of 1500mg durvalumab for patients >30 kg will be administered using an IV bag containing 0.9% (w/v) saline, with a final durvalumab concentration ranging from 1 to 20mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter. Dose of 1500mg durvalumab for patients >30 kg will be administered using an IV bag containing 0.9% (w/v) saline, with a final durvalumab concentration ranging from 1 to 20mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter.

Tremelimumab

Solution for injection/infusion

Infusion

Tremelimumab 75mg for 4 doses q28 days. Tremelimumab is administered as an IV solution of 10 mg/kg at a rate of 250 mL/hr, followed by observation for 60 minutes.

Durvalumab

Solution for infusion

Infusion

Dose of 1500mg durvalumab for patients >30 kg will be administered using an IV bag containing 0.9% (w/v) saline, with a final durvalumab concentration ranging from 1 to 20mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter. Dose of 1500mg durvalumab for patients >30 kg will be administered using an IV bag containing 0.9% (w/v) saline, with a final durvalumab concentration ranging from 1 to 20mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter.

Main cohort

Pilot

Main cohort

Pilot

The primary endpoint is defined as survival without progression (evaluated by RECIST) to 6 months, with follow-up starting from the day of trial treatment initiation.

Primary

From treatment initiation to 6-months

The primary efficacy endpoint of 6-month PFS is estimated along with a 90% one-sided lower confidence bound, calculated using the 'survival' package in R with confidence interval estimated based on the logarithmic transformation of the survival function. Analysis was performed on the main trial cohort of 10 patients. A 90% one-sided lower confidence bound above 0.15 (15%) was defined in the protocol as providing evidence of a clinically relevant treatment effect.

Main cohort v Pilot

13

Pre-specified

0.6

1-sided

Estimate of median progression free survival (PFS) time, as defined by RECIST, using data collected from treatment initiation to end of follow-up. Note that confidence interval upper bounds were not estimable- a value of 999 has been entered in place to comply with EudraCT validation rules.

Secondary

From treatment initiation until end of follow-up

RECIST Best Overall Response rates

Secondary

From treatment initiation to end of follow-up

This endpoint is used to estimate median overall survival time, from survival data captured from treatment initiation until last survival follow-up. Note that confidence interval upper bounds were not estimable - a value of 999 has been entered in place to comply with EudraCT validation rules.

Secondary

From treatment initiation until last survival follow-up

The adverse event reporting period for this trial began from the time of informed consent up to 90 days after the last dose of study drug has been administered.

Given the potential risk for delayed immune-related toxicities, safety follow-up was performed up to 90 days after the last dose of Durvalumab or Tremelimumab administration. The extended safety follow-up beyond 30 days (to 90 days) after last durvalumab or tremelimumab administration was performed either via a site visit or via a telephone call.

26

Main cohort

Pilot