JOURNAL ONKOLOGIE – STUDIE

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05908786

Studienbeginn:
Dezember 2023

Letztes Update:
09.08.2024

Wirkstoff:
Atezolizumab, Bevacizumab, Tiragolumab, Tobemstomig

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Hoffmann-La Roche

Collaborator:
-

Studienleiter

Clinical Trials
Study Director
Hoffmann-La Roche

Kontakt

Reference Study ID Number: GO44457 https://forpatients.roche.com/
Kontakt:
Phone: 888-662-6728 (U.S. and Canada)
E-Mail: global.rochegenentechtrials@roche.com» Kontaktdaten anzeigen

Studienlocations
(3 von 31)

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Medizinische Klinik und Poliklinik
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

University of Southern California (USC); Norris Comprehensive Cancer Center
90033 Los Angeles
United StatesRekrutierend» Google-Maps

University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
90404-2023 Santa Monica
United StatesRekrutierend» Google-Maps

Yale School of Medicine - Smilow Cancer Hospital - Yale-New Haven Hospital Location
06519-1110 New Haven
United StatesRekrutierend» Google-Maps

Georgetown University Medical Center
20007 Washington
United StatesRekrutierend» Google-Maps

Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
48201-2013 Detroit
United StatesRekrutierend» Google-Maps

Montefiore Einstein Cancer Center
10461 Bronx
United StatesRekrutierend» Google-Maps

Columbia University Medical Center; Herbert Irving Pavilion Location
10032 New York
United StatesRekrutierend» Google-Maps

University of Pennsylvania - Abramson Cancer Center
19104-4206 Philadelphia
United StatesRekrutierend» Google-Maps

UT Southwestern Medical Center
75390-8813 Dallas
United StatesRekrutierend» Google-Maps

Fred Hutchinson/University of Washington Cancer Consortium
98109-4433 Seattle
United StatesRekrutierend» Google-Maps

Klinikum Klagenfurt am Wörthersee
9020 Klagenfurt am Worthersee
AustriaRekrutierend» Google-Maps

Centre Georges Francois Leclerc (CGFL)
21079 Dijon
FranceRekrutierend» Google-Maps

Centre Eugene Marquis (CEM)
35042 Rennes
FranceRekrutierend» Google-Maps

Assistance Publique-Hopitaux de Paris
94800 Villejuif
FranceRekrutierend» Google-Maps

Gustave Roussy
94805 Villejuif
FranceRekrutierend» Google-Maps

CHA Bundang Medical Center
13496 Gyeonggi-do
Korea, Republic ofRekrutierend» Google-Maps

Severance Hospital, Yonsei University Health System
03722 Seoul
Korea, Republic ofRekrutierend» Google-Maps

Asan Medical Center
05505 Seoul
Korea, Republic ofRekrutierend» Google-Maps

Samsung Medical Center
06351 Seoul
Korea, Republic ofRekrutierend» Google-Maps

Auckland District Health Board (ADHB); Auckland City Hospital (ACH)
1023 Auckland
New ZealandRekrutierend» Google-Maps

Hospital Universitario Marques de Valdecilla
39008 Santander
SpainRekrutierend» Google-Maps

Clínica Universidad de Navarra
31620 Pamplona
SpainRekrutierend» Google-Maps

Hospital Clinic de Barcelona (Hospital Clinic i Provincial); Barcelona Clinic Liver Cancer (BCLC)
8036 Barcelona
SpainRekrutierend» Google-Maps

Hospital Universitario Fundacion Jimenez Diaz.
28040 Madrid
SpainRekrutierend» Google-Maps

National Cheng Kung University Hospital
70457 Tainan
TaiwanRekrutierend» Google-Maps

Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
83301 Tainan
TaiwanRekrutierend» Google-Maps

Taipei Veterans General Hospital
112 Taipei City
TaiwanRekrutierend» Google-Maps

National Taiwan University Hospital (NTUH) - Cancer Research Center
10002 Zhongzheng Dist.
TaiwanRekrutierend» Google-Maps

Belfast Health and Social Care Trust - Belfast City Hospital
BT9 7AB Belfast
United KingdomRekrutierend» Google-Maps

Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)
London
United KingdomRekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Brief Summary:

This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate

neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is

designed with the flexibility to open new treatment arms as new agents become available,

close existing treatment arms that demonstrate minimal clinical activity or unacceptable

toxicity, or modify the participant population.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Diagnosis of HCC confirmed either histologically or clinically according to AASLD

criteria for patients with cirrhosis. For participants without cirrhosis,

histological confirmation is mandatory.

- HCC that is amenable to R0 surgical resection with curative intent in the opinion of

the surgeons and oncologists or hepatologists involved in the care of the

participant. Patients presenting with resectable HCC within or beyond Milan criteria

(without extrahepatic spread or macrovascular invasion) are eligible.

- Measurable disease (at least one target lesion) according to RECIST v1.1 as

determined by the investigator

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days

prior to randomization

- Child-Pugh Class A within 7 days prior to randomization

- Negative HIV test at screening

- No prior locoregional or systemic treatment for HCC

- Adequate hematologic and end-organ function

- Documented virology status of hepatitis

- For women of childbearing potential: agreement to remain abstinent (refrain from

heterosexual intercourse) or use contraception

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or

use contraception, and agreement to refrain from donating sperm

General Exclusion Criteria:

- Presence of extrahepatic disease or macrovascular invasion

- Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other

rare variants of HCC

- History of hepatic encephalopathy if clinically significant within one year prior to

initiation of study treatment

- Moderate or severe ascites

- Active co-infection with HBV and HCV

- Known active co-infection with HBV and hepatitis D viral infection

- Prior treatment with CD137 agonists or immune checkpoint inhibitors, including

anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies

- Treatment with investigational therapy within 28 days prior to initiation of study

treatment

- Untreated or incompletely treated esophageal and/or gastric varices with bleeding or

that are at high risk for bleeding

- A prior bleeding event due to esophageal and/or gastric varices within 6 months

prior to initiation of study treatment

- Inadequately controlled hypertension

- History of hypertensive crisis or hypertensive encephalopathy

- Significant vascular disease within 6 months prior to initiation of study treatment

- History of hemoptysis within 1 month prior to initiation of study treatment

- Evidence of bleeding diathesis or significant coagulopathy

- Current or recent (<= 10 days prior to initiation of study treatment) use of

full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic

purposes

- History of abdominal or tracheoesophageal fistula, GI perforation or intra-abdominal

abscesses within 6 months prior to initiation of study treatment

- History of intestinal obstruction and/or clinical sign or symptoms of GI obstruction

- Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture

- Grade >= proteinuria

- Major surgical procedure, open biopsy, or significant traumatic injury, or abdominal

surgery, interventions or traumatic injuries, or anticipation of need of major

surgical procedure other than potentially curative liver resection

- Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)

- Serious infection requiring oral or IV antibiotics and/or hospitalization

- Active tuberculosis

Studien-Rationale

Primary outcome:

1. Major Pathologic Response (MPR) Rate (Time Frame - At the time of surgery):
MPR rate is defined as the proportion of participants with =<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review.

Secondary outcome:

1. Pathologic Complete Response (pCR) Rate (Time Frame - At the time of surgery):
pCR rate is defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review.

2. Relapse-Free Survival (RFS) (Time Frame - Surgery to the first documented recurrence of disease (up to approximately 2 years)):
RFS is defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic) according to EASL and/or RECIST v1.1, or death from any cause.

3. Event-Free Survival (EFS) (Time Frame - Randomization up to approximately 3 years):
EFS is defined as the time from randomization to any of the following events (whichever occurs first): disease progression that precludes surgery, as assessed by the investigator according RECIST v1.1; local regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.

4. Overall Survival (OS) (Time Frame - Randomization to death from any cause (up to approximately 3 years)):
OS is defined as the time from randomization to death from any cause.

5. OS Rate at 24 Months (Time Frame - Randomization up to 24 months):
OS rate at 24 months is defined as the proportion of participants who have not experience death from any cause at 24 months after randomization.

6. OS Rate at 36 Months (Time Frame - Randomization up to 36 months):
OS rate at 36 months is defined as the proportion of participants who have not experience death from any cause at 36 months after randomization.

7. Objective Response Rate (ORR) (Time Frame - Prior to surgery):
ORR is defined as the proportion of participants with a radiographic Complete Response (CR) or Partial Response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1 and HCC mRECIST. Responses will be assessed and determined according to RECIST v1.1 and HCC mRECIST but are not required to be confirmed by subsequent imaging assessments.

8. Proportion of Participants Downstaged to Within Milan Criteria (Time Frame - Prior to surgery):
Proportion of participants downstaged to within Milan criteria (for participants beyond criteria at randomization). Within Milan criteria is defined as single tumor <= 5 cm or 2 - 3 nodules all <= 3 cm.

9. R0 Resection Rate (Time Frame - At the time of surgery):
R0 resection rate (proportion of resected participants obtaining an R0 resection). R0 resection is defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.

10. Percentage of Participants With Adverse Events (Time Frame - Up to approximately 3 years after first participant enrolled)

11. Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events (Time Frame - >28 days from surgical restaging visit, anticipated up to 56 days):
Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit).

12. Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification (Time Frame - Surgery to treatment completion/discontinuation (up to approximately 2 years)):
Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa.

13. Post-Operative Mortality (Time Frame - Within 90 days after surgery):
Post-operative mortality is defined as death within 90 days after surgery

Studien-Arme

Experimental: Atezo + Bev
Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Experimental: Atezo + Bev +Tira
Participants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Experimental: Tobe + Bev
Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Geprüfte Regime

Atezolizumab (Tecentriq):
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Bevacizumab (Avastin):
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Tiragolumab:
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
Tobemstomig (RO7247669):
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Quelle: ClinicalTrials.gov

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