Adjuvant Therapy with Pembrolizumab Versus Placebo in Participants with Hepatocellular Carcinoma and Complete Radiological Response after Surgical Resection or Local Ablation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 May 2019 → 30 Sep 2025

Decision date (initial)

2023-07-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501971-24-00

EudraCT number

2018-004800-20

WHO UTN

U1111-1282-6370

ClinicalTrials.gov

NCT03867084

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Efficacy, Safety, Prophylaxis

1. To compare Recurrence-Free Survival (RFS)
2. To compare Overall Survival (OS)

Secondary objectives 3

1. To evaluate the safety and tolerability
2. To compare time to deterioration (TTD) and score change from baseline in global quality of life (QoL) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) global health status/QoL scale and EORTC QLQ-HCC18
3. To characterize health utilities using the EuroQoL-5 Dimension Questionnaire, 5-Level (EQ-5D-5L) health utility scores

Conditions and MedDRA coding

Adjuvant treatment of HCC

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Has a diagnosis of HCC by radiological criteria and/or pathological confirmation.
2. Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and CT or MRI of the pelvis) confirming complete radiological response ≥4 weeks after complete surgical resection or local ablation. Randomization needs to occur within 12 weeks of the date of surgical resection or local ablation.
3. Has no radiologic evidence of disease prior to enrollment.
4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to Cycle 1, Day 1.
5. Has a Child-Pugh class A liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
6. Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 days prior to Cycle 1, Day 1.
7. Has controlled hepatitis B (Hep B).
8. Has recovered adequately from toxicity and/or complications from the local intervention (surgical resection or local ablation) prior to starting study treatment.
9. If female, is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a WOCBP and using a contraceptive method that is highly effective or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a negative pregnancy test within 72 hours before the first dose of study treatment).
10. If undergoing surgical resection, has submitted a tumor tissue sample during Screening.
11. Has adequate organ function.

Exclusion criteria 20

1. Has a known additional malignancy that is progressing or has required active antineoplastic treatment (including hormonal) or surgery within the past 3 years.
2. Has had esophageal or gastric variceal bleeding within the last 6 months.
3. Has clinically apparent ascites on physical examination.
4. Has had clinically diagnosed hepatic encephalopathy in the last 6 months.
5. Has received local therapy to liver ablation other than with radiofrequency or microwave ablation.
6. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
7. Has an active infection requiring systemic therapy.
8. Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study entry.
9. Has a known history of human immunodeficiency virus (HIV) infection.
10. Has known active tuberculosis (TB; Bacillus tuberculosis).
11. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
12. Has received prior systemic anti-cancer therapy for HCC including investigational agents.
13. Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5) Oncological surgical therapy; or systemic glucocorticoids for any purpose other than to modulate symptoms from an AE that is suspected to have an immunologic etiology.
14. Has received a live vaccine within 30 days prior to the first dose of study treatment.
15. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to Cycle 1, Day 1.
16. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.
17. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
18. Has an active autoimmune disease that has required systemic treatment in past 2 years.
19. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
20. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Recurrence-Free Survival (RFS)
2. Overall Survival (OS)

Secondary endpoints 5

1. Percentage of participants who experience an adverse event (AE)
2. Percentage of participants who discontinue study treatment due to an AE
3. Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Overall Scores and Subscale Scores
4. Change from Baseline in EORTC QLQ-Hepatocellular Carcinoma Module (EORTC QLQ-HCC18) Scale Score
5. Change from Baseline in European Quality of Life (EuroQoL)-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) Health Utility Score

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Usha Malhotra

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Usha Malhotra

Third parties 8

Locations

11 EU/EEA countries · 50 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 129 files

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

Application history

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