ROSETTA HCC-206: An Open-Label, Multi-Center, Randomized Phase I/II Study of Pumitamig Alone or In Combination With Ipilimumab in Participants With First-Line Advanced or Unresectable Hepatocellular Carcinoma (HCC)

Study Identifier:
CA266-0006
CT.gov Identifier:
NCT07291076
EudraCT Identifier:
202552360233
EU Trial (CTIS) Number:
2025-523602-33-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

To evaluate the safety and tolerability of Pumitamig alone or in combination with Ipilimumab in participants with first-line advanced or unresectable Hepatocellular Carcinoma (HCC)

To evaluating Pumitamig as a single agent or in combination with ipilimumab in participants with first-line advanced or unresectable hepatocellular carcinoma (HCC)

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Liver
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting

Requirements information
Inclusion criteria
  • Participants must have a histologically confirmed diagnosis of locally advanced or unresectable Hepatocellular Carcinoma (HCC).
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Participants must have no prior systemic therapy for advanced/ unresectable HCC.
  • Participants must have measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Participants must sign and date the written ICF approved by the IRB/IEC in accordance with regulatory, local, and institutional guidelines.
  • Participants must have histologically confirmed HCC.
  • At least 5 tumor tissue slides must be submitted.
  • Participants must have advanced HCC
  • Participants must have at least one previously untreated lesion measurable by RECIST version 1.1.
  • Participants must have never received systemic drug therapy for advanced/unresectable HCC.
  • Participants were eligible for enrollment if they had non-virus-associated HCC, or HBV-HCC or HCV-HCC as defined below: a) HBV-HCC: i. Recovered HBV infection, characterized by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen; or ii. Chronic HBV infection, characterized by detectable HBV surface antigen or HBV DNA. Participants with chronic HBV infection must be receiving antiviral therapy, and their HBV DNA levels must be less than 500 IU/mL.
  • b) HCV-HCC: i. Recovered HCV infection, characterized by detectable HCV antibodies but undetectable HCV RNA; or ii. Chronic HCV infection, characterized by detectable HCV RNA.
  • Child-Pugh Grade A
  • ECOG PS score is 0 or 1.
  • Life expectancy ≥ 3 months
  • At the time of signing up for the ICF, participants must be 18 years of age or older, or of legal adult Age as defined by local regulations.
  • Men and women of childbearing age participating in the study need to take necessary precautions against contraception.
  • Age of Participant must be ≥ 18 years of age, or legal adult age according to the local regulation inclusive, at the time of signing the ICF.
  • People with a certain kind of advanced liver cancer (HCC) that can't be removed by surgery.
  • People who can still do most everyday things on their own.
  • People whose liver is working well.
  • People who haven't had certain treatments for their liver cancer before.
  • People who have at least one tumor that shows up on a scan
Exclusion criteria
  • Participants must not have significant bleeding or coagulation disorders or other obvious bleeding risk evidence.
  • Participants must not have an organ transplant or autoimmune disease.
  • Other protocol-defined Inclusion/Exclusion criteria apply.
  • Histological subtypes: fibrolamellar HCC, sarcomatoid HCC, or mixed HCC/cholangiocarcinoma.
  • Previous liver transplant recipient
  • Imaging findings suggest a central tumor with invasion, necrosis, or cavitation of large blood vessels, indicating a high risk of bleeding.
  • Liver complications: a) Grade 2 hepatic encephalopathy occurring within 12 months. b) Clinically significant ascites requiring treatment or ongoing prophylactic treatment.
  • c) Presence of untreated or incompletely treated esophageal and/or gastric varices with bleeding or a high risk of bleeding. Participants must undergo esophagogastric-duodenal endoscopy (EGD), and all varices of all sizes (from smallest to largest) must have been assessed and treated according to local standards prior to enrollment. Participants who have undergone EGD within 6 months prior to the start of study treatment do not need to repeat the examination.
  • Untreated known CNS metastases, including compression of the brain, pia mater, and/or spinal cord.
  • Known or suspected active autoimmune diseases
  • Systemic immunosuppressive therapy (e.g., >10 mg/day prednisone or equivalent) is required within 14 days prior to the first dose of the study intervention.
  • Pre-existing thyroid dysfunction that cannot be maintained within the normal range by medication
  • Concurrent malignant tumors requiring treatment or a history of active malignant tumors within the past 2 years.
  • History of interstitial lung disease or lung inflammation
  • Pleural or pericardial effusion requiring repeated therapeutic drainage procedures
  • Uncontrolled or significant cardiovascular disease
  • Clinically significant cardiovascular diseases, including but not limited to congenital long QT syndrome.
  • Risk of clotting and bleeding
  • Evidence of active or uncontrolled infection requiring systemic antimicrobial, antiviral, or antifungal therapy within ≤14 days prior to the first dose of the study intervention (excluding viral infections presumed to be related to the underlying tumor).
  • Participants were known to be HIV positive and had an AIDS-defined opportunistic infection in the past year, or had a current CD4 count of <350 cells/μL.
  • Hepatitis a) HBV: Positive for hepatitis B surface antigen (HBsAg) and HBV DNA ≥500 IU/mL. b) Co-infection: Active HBV + HCV or HBV + hepatitis D virus (HDV) co-infection. c) Participants receiving HCV antiviral therapy must consult a medical monitor.
  • Any serious or uncontrollable medical condition
  • Researchers considered any other medical, psychiatric, or social condition that would contraindicate participation in the study.
  • 20
  • :
  • twenty one Unable to comply with the restrictions and contraindications listed in the protocol's prior and concomitant treatments
  • 21
  • :
  • twenty two Life-threatening toxicity resulting from previous systemic cancer treatment, unless recurrence is considered unlikely.
  • 22
  • :
  • twenty three A history of grade ≥3 immune-mediated adverse events leading to discontinuation of previous immunotherapy
  • 23
  • :
  • twenty four History of solid organ, tissue, or allogeneic hematopoietic stem cell transplantation
  • The study participants had received treatment with potent cytochrome P450 (CYP)3A4 inducers (e.g., rifampicin, St. John's wort) within one week prior to the first dose of the intervention.
  • Treatment with anticoagulants or antiplatelet agents that may increase the risk of bleeding.
  • Patients must have received radiation therapy within 4 weeks prior to the first dose of the study intervention. Palliative radiation therapy must have been completed ≥2 weeks prior to the first dose of the study intervention.
  • Received live/attenuated vaccine within 28 days prior to the first dose of the study intervention.
  • Those who used over-the-counter or prescription supplements within 14 days prior to the first dose of the study intervention.
  • Evidence of organ dysfunction or any clinically significant abnormality that is inconsistent with the target population in physical examination, vital signs, ECG, or clinical laboratory tests, and which, if involved in the study, may expose the participant to unacceptable risks or interfere with the study intervention or follow-up.
  • Laboratory test results that do not meet the requirements of the protocol
  • Known or suspected allergy to any investigational drug or investigational drug ingredient
  • History of severe hypersensitivity to any monoclonal antibody
  • Simultaneously participating in another interventional clinical trial
  • Prisoners or participants in involuntary imprisonment
  • People with rare types of liver cancer.
  • People who have serious bleeding problems or are likely to bleed easily.
  • People who have had an organ transplant or have immune system diseases.
  • People with high blood pressure that can't be controlled, even with medicine.
  • People whose urine has too much protein (sign of kidney problems).
  • People taking strong blood-thinning medicines.
  • Key exclusion criteria include significant bleeding or coagulation disorders, evident bleeding risk, organ transplant history, or active autoimmune disease.

Clinical Study Information for Healthcare Providers

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Juan José Soto
Status
Recruiting
Condition(s) Treated at Site
Liver