Patients must have an HCC diagnosis (initial, recurrent, progressive and/or refractory to other therapies) by at least one criterion listed below =< 360 days prior to study entry\r\n* Pathologically (histologically or cytologically) proven diagnosis of HCC\r\n* At least one solid liver lesion or vascular tumor thrombosis (involving portal vein, inferior vena cava [IVC] and/or hepatic vein) > 1 cm with arterial enhancement and delayed washout on multi-phasic computerized tomography (CT) or magnetic resonance imaging (MRI) in the setting of cirrhosis or chronic hepatitis B or C without cirrhosis\r\n* For patients whose CURRENT disease is vascular only: enhancing vascular thrombosis (involving portal vein, IVC and/or hepatic vein) demonstrating early arterial enhancement and delayed washout on multi-phasic CT or MRI, in a patient with known HCC (diagnosed previously < 720 days)
Prior sorafenib use > 60 days and/or grade 3 or 4 sorafenib related toxicity; note that prior chemotherapy for HCC or a different cancer is allowable
Total sum of maximum diameters of each definite parenchymal hepatocellular carcinomas within the liver or maximum diameter of a single conglomerate HCC > 20 cm
More than 5 discrete intrahepatic parenchymal foci of definite HCC
Measureable common or main branch biliary duct involvement with HCC
Patients must have confirmed hepatocellular carcinoma (HCC) by histopathology or imaging criteria according to AASLD guidelines.
For Phase 2, must have one of the following tumor types: recurrent or refractory NSCLC (any histology), or HCC with elevated alpha-fetoprotein (AFP) ?200 nanogram/milliliter (ng/mL).
For HCC:
Participants with a first diagnosis of HCC who have undergone a curative resection or ablation
Participants are eligible to enroll if they have non-viral related-HCC, or if they have HBV-HCC, or HCV-HCC
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
Participants previously receiving any prior therapy for HCC, including loco-regional therapies
Confirmed diagnosis of hepatocellular carcinoma (HCC)
HCC for which no other appropriate therapy is available. Note: Expansion Part: No prior systemic therapy for advanced/unresectable HCC
Subjects must have a diagnosis of measurable advanced or metastatic hepatocellular carcinoma; advanced HCC is defined as disease not amenable to surgery, ablation, transplant, or embolic therapy
Histologically confirmed diagnosis of hepatocellular carcinoma (mixed HCC/cholangiocarcinoma is allowed)
Patients must have HCC limited to the liver; there must be no definitive clinical or radiographic evidence of extrahepatic HCC; portal lymphadenopathy is permitted as lymphadenopathy is commonly associated with cirrhosis unrelated to malignancy
Patients with locally advanced HCC not eligible for curative therapies
Patient who has received previous systemic therapy or transarterial chemoembolization (TACE) for HCC
Presence of at least one measurable lesion according to RECIST v1.1. c-i) FGF401 single agent-Phase I and Phase II, Group 3: Patients with HCC or advanced solid tumors, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. c-ii) FGF401 single agent-Phase II, Groups 1 and 2: HCC patients previously treated with sorafenib for advanced HCC with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment c-iii) FGF401 in combination with PDR001:Advanced HCC patients who have received up to 2 previous lines of systemic treatment and one treatment must have included sorafenib with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment
Have a diagnosis of hepatocellular carcinoma (HCC) and high risk for HCC recurrence
Concurrent administration of systemic therapy for HCC
HCC (unresectable hepatocellular carcinoma) histopathological diagnosis confirmation based on tumor tissue
No prior systemic therapy for HCC
Histology and/or cytology confirmed HCC per the enrolling institution; subjects in Cohort 1 are permitted to enroll without confirmation of HCC as long as imaging Liver Imaging Reporting and Data System (LiRAD)s criteria are met and a biopsy is scheduled prior to or the day of the deb-TACE procedure; HCC confirmation must be completed prior to initiation of nivolumab for all cohorts; if a patient is found to not have confirmed HCC, they will be removed from the study
Confirmed hepatocellular carcinoma (HCC) by one of the following: \r\n* Histopathology\r\n* One radiographic technique that confirms a lesion >= 1 cm with arterial hypervascularization with washout on delayed phase
COHORT B, GROUP 6: HEPATOCELLULAR CARCINOMA: Patients with hepatocellular carcinoma do not need to have histologic confirmation of disease as long as they meet the radiologic criteria for diagnosis of hepatocellular carcinoma (HCC) (evidence of arterial phase enhancement with corresponding venous or delayed phase wash out)
Patient must have a histologically confirmed diagnosis hepatocellular carcinoma; known fibrolamellar HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC will be excluded
Patient who has received previous systemic therapy for HCC
Progressed on, be intolerant of, or refused sorafenib (for hepatocellular carcinoma [HCC]), second line treatment and beyond for cholangiocarcinoma or gemcitabine-based chemotherapy for biliary tract cancer.
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
Any prior systemic therapy for HCC
Known fibrolamellar or mixed HCC-cholangiocarcinoma histology
Confirmed HCC based on histopathological findings from tumor tissues. Unresectable HCC with diagnosis confirmed pathologically or with noninvasive methods.
Diagnosis of primary liver malignancy including hepatocellular carcinoma (HCC) or cholangiocarcinoma by characteristic imaging findings on computed tomography (CT) or MRI, clinical presentation, and/or pathologic confirmation of diagnosis; subjects with other current or prior malignancies are eligible for this study
Fibrolamellar carcinoma or mixed HCC
Patients must have no prior history of treatment for HCC (treatment naive).
Patients must not have received prior anticancer therapy with anti-CLTA-4 or anti-PD1 for HCC. Patients receiving any concomitant systemic therapy for HCC are excluded
Participants who have received prior sorafenib or anti-PD1 therapy for HCC
Pathologic diagnosis of hepatocellular carcinoma (including fibrolamellar variants and biphenotypic tumors with a hepatocellular carcinoma [HCC] component)
Prior systemic therapies for HCC are allowed but not required
Be scheduled for sub-lobar radioembolization therapy of a previously untreated HCC mass < 6 cm visible on grayscale ultrasound
Patients with diagnoses of hepatocellular carcinoma (HCC) according to European Association for the Study of Liver disease (EASL) criteria for diagnosis; regional lymphadenopathy will be allowed\r\n* Any virus status accepted (e.g. hepatitis C, etc.)\r\n* Any prior liver treatment
Patients within unresectable HCC
Patients with resectable HCC
Histological or radiologic diagnosis of advanced (unresectable or metastatic) HCC with Child-Pugh A or Child Pugh B7 cirrhosis:\r\n* The diagnosis of HCC will be made according to the European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer Clinical Practice Guidelines (EASL–EORTC CPG) and according to successive modifications of the American Association for the Study of Liver Disease (AASLD) practice guidelines \r\n* Pathological diagnoses of HCC will be made according to the International Working Party criteria
Cytologically or histologically confirmed advanced or metastatic HCC; if no histological diagnosis, patient must have imaging studies compatible with HCC
Total maximal sum of hepatocellular carcinomas or a single conglomerate HCC > 20 cm
Measurable common or main branch biliary duct involvement with HCC
Patients who have received sorafenib or other systemic therapies for treatment of HCC in the past
Subjects with advanced hepatocellular carcinoma (HCC) with no curative option
Have histologically or cytologically documented HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required; for subjects without cirrhosis histological confirmation is mandatory
Portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
Had prior systemic therapy for HCC other than sorafenib, or intercurrent local therapy to the liver tumor between sorafenib and study drug
Patient must have advanced hepatocellular carcinoma; fibrolamellar HCC is not allowed; hepatocellular carcinoma should be confirmed by at least one of the following:\r\n* Tissue diagnosis\r\n* The presence of one or more liver lesions measuring >= 2 cm in longest diameter, showing characteristic arterial enhancement and venous washout using arterial-phase contrast enhanced imaging, and a clinical history of cirrhosis
More than one line of prior systemic therapy for HCC
Patients must have a diagnosis of hepatocellular carcinoma (HCC) confirmed by American Association for Study of Liver Diseases (AASLD) guidelines with a Childs-Pugh score of A or B (but, =< Childs score B8)\r\n* NOTE: If the patient does not have histological confirmation of disease by biopsy, diagnosis of HCC must be documented with approval by a tumor board or other multidisciplinary conference
Patients must have histopathological confirmation of hepatocellular carcinoma (HCC) or biliary tract carcinoma (BTC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study OR histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma); fibrolamellar variant is also allowed; the term BTC includes intra- or extrahepatic cholangiocarcinoma, gallbladder cancer or ampullary cancer
No prior treatment of current HCC; however, recurrent HCC after resection may be included
Part 2 Group B is restricted to HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
Subjects who have radiographic or histological diagnosis of hepatocellular cancer (HCC), with advanced stage disease that is not amenable to curative surgical resection; patients without histologic diagnosis must meet the radiographic criteria for HCC
Patients who have received sorafenib or other systemic therapies for treatment of HCC in the past
Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required
Histological or radiologic confirmation of advanced or metastatic HCC:\r\n* The diagnosis of HCC will be made according to the guidelines of the Barcelona-2000 European Association for the Study of the Liver (EASL) Conference (Bruix et al 2001) and according to successive modifications of the American Association for the Study of Liver Disease (AASLD) (Bruix et al 2005) \r\n* Pathological diagnoses of HCC will be made according to the International Working Party criteria (International Working Party 1995)
HCC not amenable to surgical resection, liver transplantation, chemoembolization, or ablation therapy
Patients must have a diagnosis of hepatocellular carcinoma confirmed by at least one of the following: \r\n* Histological confirmation; \r\n* Imaging results consistent with cirrhosis and at least one solid liver lesion of > 2 cm with early enhancement and delayed washout (American Association for the Study of Liver Diseases [AASLD] criteria for diagnosis of hepatocellular carcinoma [HCC]);\r\n* Alpha fetoprotein level > 400 ng/mL and evidence of at least one solid liver lesion > 2 cm, regardless of specific imaging characteristics on magnetic resonance imaging (MRI)
Infiltrative form of HCC on imaging; if there is at least one measurable lesion per modified RECIST (mRECIST) criteria and otherwise patient is eligible for the study, the patient can be enrolled
Diagnosis of HCC:
For subjects without underlying cirrhosis at the time of diagnosis, diagnosis of HCC documented by cytology and/or histology.
For subjects with underlying cirrhosis at the time of diagnosis, diagnosis of HCC established according to the American Association for the Study of Liver Diseases Practice Guideline algorithm (Appendix E).
HCC is advanced, ie, treatment-refractory or metastatic, and no standard therapies are expected to be curative.
Receipt of no, or of >1, prior systemic drug therapies for HCC.
Active malignancy other than HCC.
Diagnosed with a single HCC lesion ? 3.0 cm but ? 7.0 cm in maximum diameter based on diagnosis at screening.
Subjects not meeting the AASLD criteria for HCC will need a biopsy to confirm HCC prior to randomization.
Have previously received therapeutic treatment for HCC outside the study protocol or is expected to receive concomitant HCC treatment prior to PFS event.
Diagnosis of intrahepatic malignancy including but not limited to HCC; the histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as alpha-fetoprotein (AFP) and clinical findings
Patient diagnosed with hepatocellular carcinoma in both lobes of the liver by one of the following methods\r\n* Pathologically confirmed hepatocellular carcinoma (HCC) by biopsy, OR\r\n* HCC > 2 cm with classic radiographic findings of arterial phase enhancement with venous phase washout and pseudocapsule formation on contrast enhanced magnetic resonance imaging (MRI) or computed tomography (CT), OR\r\n* Lesion greater than 2 cm with probable imaging features of HCC and imaging findings of cirrhosis and/or portal hypertension or a serum alpha fetoprotein (AFP) greater than 200 ng/mL
Unilobar HCC
Histological/cytological diagnosis of primary HCC
Diagnosis of unresectable intrahepatic HCC. The histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as alphafetoprotein (AFP)^21 and clinical findings. Guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) describe in detail the approach and algorithm for diagnosing HCC.
Histologically or cytologically confirmed, or clinically diagnosed based on currently accepted standards, cancer metastatic to the liver or HCC that is not amenable at the time of enrollment to resection, transplant or other potentially curative therapy.
Primary HCC amenable to resection, transplant or other potentially curative therapy.
Pathologically newly diagnosis HCC, which is deemed resectable and resected
Histologically confirmed diagnosis of HCC
No prior systemic therapy for HCC (with the exception of HCC patients enrolled in the safety run-in substudy [Japan only])
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology
Patients with advanced HCC not amenable for surgical or loco-regional treatment
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
Subject has a confirmed pathologic diagnosis of Hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) Guidelines.
Subjects who have progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.
Subject has received more than 2 previous systemic therapies for Hepatocellular carcinoma (HCC).
Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases (AASLD) criteria in patients with a confirmed diagnosis of cirrhosis.
Prior systemic therapy for HCC; prior exposure to regorafenib.
Expansion cohort (HCC): histologically or cytologically confirmed diagnosis of hepatocellular carcinoma who are Child-Pugh class A and who were previously treated with sorafenib or refused sorafenib
Pathologically confirmed diagnosis of stage IIIB/IV recurrent squamous cell NSCLC defined as not amenable to local curative therapy (surgery, radiation, or chemoradiation), and refractory to systemic therapy OR Pathologically or radiologically (fulfilling non-invasive criteria) confirmed diagnosis of HCC not amenable to resection (partial hepatectomy or liver transplantation) or local therapy with curative intent (e.g. radiofrequency ablation) and must not be a liver transplant candidate as defined according to Milan criteria
HIV infection, active hepatitis B or C infection. History of treated hepatitis B or C is permitted if the viral load is undetectable. HCC patients with controlled or chronic stable HBV infection will be eligible for screening. HCC patients with HBV infections who are not on anti-HBV treatment will be excluded from the study. HCC subjects with HCV infections will be allowed for screening; however, subjects with both HBV and HCV infections will be excluded for screening
For Dose Expansion Cohort: HCC patients only: HCC confirmed by biopsy OR diagnosed by clinical and radiologic criteria; all of the following criteria must be met or a biopsy is required:\r\n* Known cirrhosis or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection\r\n* Hypervascular liver masses > 2 cm, and either serum alpha-fetoprotein (AFP) > 400 ng/ml\r\n* AFP > three times normal and doubling in value in the antecedent 3 months\r\n* In the expansion cohort, prior treatment with sorafenib as first-line therapy allowed
Patients with hepatocellular carcinoma are eligible for this trial; hepatocellular carcinoma is defined as having at least one of the following:\r\n* Biopsy proven hepatocellular carcinoma (HCC); or\r\n* A discrete hepatic tumor(s) as defined by the Barcelona criteria – for cirrhotic patients, > 1 cm with arterial hypervascularity and venous or delayed phase washout on computed tomography (CT) or MRI
Diagnosis of liver-only HCC based on European Association for the Study of the Liver (EASL) criteria (radiographic lesion appearance on contrast-enhanced computed tomography [CT] or magnetic resonance imaging [MRI], i.e. enhancement on early arterial phase, washout on portal venous phase with or without associated elevation of serum AFP level > 200 U/ml) or histologic confirmation of HCC diagnosis, whichever is applicable
Patients must have histologically diagnosed American Joint Committee on Cancer (AJCC) stage II, III, or IV HCC not eligible for curative resection, transplantation, or ablative therapies\r\n* Cases with mixed, composite, or combined HCC-cholangiocarcinoma histology are eligible with approval from study chair and provided the treating investigator believes it is in the best interest of the patient to treat the tumor with therapy targeted towards the HCC component of tumor based upon review of pathology and clinical\r\ncharacteristics
No prior systemic cytotoxic chemotherapy or targeted therapy (including sorafenib) for HCC
Biliary tract cancers or fibrolamellar variant tumors are excluded\r\n* Cases with mixed, composite, or combined HCC-cholangiocarcinoma histology are eligible with approval from study chair and provided the treating investigator believes it is in the best interest of the patient to treat the tumor with therapy targeted towards the HCC component of tumor based upon review of pathology and clinical characteristics
Prior systemic cytotoxic therapies for HCC (chemoembolization is permitted if inclusion criteria are met)
Diagnosis of liver confined hepatocellular carcinoma (HCC) confirmed by histology or American Association for the Study of Liver Diseases (AASLD) guidelines\r\n* Lesions < 1 cm in diameter have a low likelihood of being malignant and should be followed; lack of growth over 1-2 years suggests it is not HCC\r\n* Alpha-fetoprotein (AFP) > 200 and radiological evidence (arterial hypervascularity) of lesion > 2 cm does not require biopsy\r\n* Two imaging modalities (triphasic computed tomography [CT], MRI, ultrasound, angiography) demonstrating “arterial hypervascularity” in the background of cirrhosis does not require biopsy\r\n* One imaging modality with a lesion with arterial hypervascularity with wash out in early or delayed venous phase, does not require a biopsy\r\n* Atypical appearances on imaging requires a biopsy\r\n* Non-conclusive biopsy requires closer monitoring \r\n* For non-cirrhotics (by biopsy or imaging findings), diagnosis of HCC requires biopsy
Patients must have hepatocellular carcinoma (HCC) with one of the following: \r\n* Microvascular/macrovascular invasion, \r\n* Tumor outside of Milan criteria, \r\n* Poor tumor differentiation; \r\n* Elevated surrogate markers (AFP > 500 or PIVKA [DCP] > 400) pre transplant and with biopsy proven HCC prior to orthotopic liver transplantation (OLT) or on explants
Patients with local lymph node metastases\r\n* However, patients with high risk HCC who have been down-staged prior to OLT and show 100% necrosis on explant are eligible as long as there is biopsy proven HCC
Patients with fibrolamellar HCC, cholangiocarcinoma, and combined HCC-cholangiocarcinoma
Prior use of any systemic chemotherapy for HCC, with the exception of sorafenib
Prior use of systemic investigational agents for HCC
Has a HCC diagnosis confirmed by radiology, histology or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib, prior to the start of study drug.
Phase 2 expansion: HCC
Must have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
Histological or cytological diagnosis of HCC.
Progression following at least 1 prior systemic treatment for HCC.
Receipt of more than 2 prior systemic therapies for advanced HCC.
Hepatocellular carcinoma (HCC)\r\n* Not eligible for curative attempt resection or liver transplant
Locoregional therapy for hepatocellular carcinoma (HCC) must be completed at least 4 weeks prior to the baseline scan
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants should have Child-Pugh stage A.
Participants with HCC that:
Have known HCC with fibro-lamellar or mixed histology.
Unresectable HCC confirmed by histology or by non-invasive AASLD criteria
History of previous or concurrent cancer other than HCC unless treated curatively 5 or more years prior to entry
Prior systemic treatment for the treatment of HCC, including sorafenib
Known chronic hepatitis B or C virus (HBV/HCV) infection, unless comorbidity in subjects with Hepatocellular carcinoma (HCC).
For Cohort 1: has histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) based on pathology report
For Cohort 2: has an HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
Has portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
For Cohort 1: had prior systemic therapy for HCC other than sorafenib, or intercurrent local therapy to the liver tumor between sorafenib and study drug
Participants with diagnosis of HCC.
Subjects must have confirmed diagnosis of unresectable HCC with any of the following criteria:
Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteria
Imaging findings for HCC corresponding to any of the following:
Patients with the diagnosis of hepatocellular carcinoma (HCC) currently being evaluated for liver transplantation and considered for downstaging
Advanced tumoral disease, defined as vascular invasion, extrahepatic spread, or diffuse HCC (50% liver involvement)
Has histopathologically or cytologically confirmed HCC, Child-Pugh Class A, with documented disease progression during or after discontinuation of sorafenib therapy, or intolerance of sorafenib therapy, and an ?-fetoprotein (AFP) ? 1.5x upper limit of normal
Subject has a documented diagnosis of advanced HCC of any etiology.
Subject has adequately recovered from toxicities due to prior HCC therapy to ? grade
Subject has fibrolamellar variant of HCC.
Subject has a history of a non-HCC malignancy with the following exceptions:
History of recurrent bacterial infections unrelated to hepatocellular carcinoma (HCC) (particularly skin or lung)
Outpatients with histologically/cytologically documented or radiographically diagnosed unresectable hepatocellular carcinoma (HCC) who are candidates for systemic therapy and for whom a decision to treat with sorafenib has been made; radiographic diagnosis needs typical findings of HCC by a radiographic method, i.e. on multi-dimensional dynamic computed tomography (CT), CT hepatic arteriography (CTHA)/CT arterial portography (CTAP) or magnetic resonance imaging (MRI)
Part A2 only: Patients with histological or cytological diagnosis of HCC who have had 0 to 2 prior lines of systemic therapy (progressed or intolerant to approved HCC standard of care treatment).
No prior systemic therapy for HCC
History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
Patients with histological or cytologically documented hepatocellular carcinoma (HCC) (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects is required; for subjects without cirrhosis histological confirmation is mandatory
Prior systemic therapy for the treatment of HCC, including sorafenib
Patients must have histopathological confirmation of HCC or (Cohort E only) biliary tract carcinoma (BTC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC (or biliary tract carcinoma in Cohort E); fibrolamellar variant is also allowed; for cohort E, the term BTC includes intra- or extrahepatic cholangiocarcinoma, gallbladder cancer or ampullary cancer, as long as there is an intrahepatic component amenable to RFA
Participants must have histologically or/and radiologically confirmed advanced hepatocellular carcinoma (HCC); radiographic diagnosis needs typical findings of HCC by radiographic method i.e. on multi-dimensional dynamic computed tomography (CT), CT hepatic arteriography (CTHA)/CT arterial portography (CTAP) or magnetic resonance imaging (MRI)
Diagnosis of hepatocellular carcinoma (HCC) confirmed histologically, excluding mixed HCC histology (e.g. HCC plus cholangiocarcinoma) or fibrolamellar variant
Advanced staged HCC (unresectable and not amenable to local or regional therapy; or metastatic HCC); the diagnosis of HCC should be based on at least one of the following:\r\n* Magnetic resonance imaging (MRI) or computed tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion measuring >= 2 cm, with characteristics arterial enhancement and venous washout regardless of alpha-fetoprotein (AFP) levels\r\n* AFP >= 400 ng/mL AND evidence of at least one solid liver lesion >= 2 cm regardless of specific imaging characteristics on CT or MRI\r\n* Histological/cytology biopsy confirming HCC
Histologically confirmed advanced HCC
No prior systemic regimens for HCC
Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases criteria in patients with a confirmed diagnosis of cirrhosis
Prior systemic treatment for HCC, except sorafenib.
Known to be Hepatitis B or C positive (except HCC patients)
Have histological evidence of a diagnosis of HCC not amenable to curative surgery
Known HCC with fibro-lamellar or mixed histology
Patients with chronic Hepatitis B and C infection. For patients with hepatocellular carcinoma (HCC), the presence of chronic HBV and HCV is NOT an exclusion. Patients must have a viral titer <50 IU/ml x 2 at a minimum of 2 weeks apart.
Diagnosis of HCC
Advanced tumoral disease (vascular invasion or extrahepatic spread, portal vein thrombosis of bland or malignant origin), or diffuse HCC, defined as 50% liver involvement).
Diagnosis of HCC
Locally advanced HCC
Prior intra-arterial embolization, chemotherapy or systemic therapy for HCC.
Histologic diagnosis of liver-confined fibrolamellar or non-fibrolamellar hepatocellular carcinoma (HCC)
Early stage hepatocellular carcinoma (HCC) diagnosed based on the typical hallmark of HCC (hypervascular in the arterial phase with washout in the portal venous or delayed phases)
Documented complete response to HCC treatment.
Advanced unresectable hepatocellular carcinoma with branch portal vein thrombosis (confirmed by non-invasive criteria EASL/AASLD, mandatory by histology in non-cirrhotic patients); can be naive or recurrent HCC after curative treatment (> 6 months before randomization)
At least one uni-dimensional HCC target lesion assessable by CT or MRI according to RECIST 1.1
Confirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).
Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to study entry; this diagnosis must be confirmed by pathology review at a Dana-Farber (DF)/Harvard Cancer Center (HCC) institution
Diagnosis of fibrolamellar HCC or tumors of mixed histology.
Confirmed to have HCC as described by the American Association for the Study of Liver Disease (AASLD).
Prior chemotherapy, immunotherapy, investigational therapeutic agent, or other therapy used to treat HCC within 4 weeks before the first scheduled administration of RO7070179.
Subjects must have histologically or cytologically confirmed advanced solid tumor. However, Hepatocellular Carcinoma (HCC) subjects are allowed without histological confirmation as long as there is radiological diagnosis as per standard criteria
Histologically confirmed HCC
Prior systemic anticancer treatment for advanced HCC (except for sorafenib as described in the inclusion criteria)
Prior diagnosis of HCC confirmed histologically.
Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional therapies.
Other primary solid tumor with no known active disease in the opinion of the investigator that will not affect patient outcome in the setting of current HCC diagnosis.
Histologically confirmed HCC that is inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), and not eligible for local therapy
More than 1 prior systemic regimen (prior MET inhibitors/antibodies are not allowed; experimental systemic therapy for inoperable HCC given before or after sorafenib counts as separate regimen and is not allowed)
Histologically confirmed diagnosis of advanced solid tumor (dose escalation component) or metastatic melanoma (uveal or cutaneous) (doses escalation and MTD expansion components) or platinum-resistant (tumor progression within a year after the completion of platinum-based therapy) ovarian carcinoma (high grade serous, endometrial or poorly differentiated endometrioid) or HCC that has failed treatment with sorafenib or did not tolerate sorafenib or refused sorafenib, or HCC with coexistent BCT that has or has not been treated with chemotherapy, or BCT that has or has not been treated with chemotherapy. For HCC and HCC with coexistent BCT, cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix C). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.
Ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only tissue either from an archived specimen or from a new biopsy of sufficient amount and quality should be available for IHC determination of ASS status to be performed retrospectively for the ovarian cancer, or HCC, or HCC with coexistent BCT, or BCT only cohorts. Subjects with no tissue available would require a biopsy.
Cytological or histological confirmed diagnosis of advanced hepatocellular or renal cell carcinoma; HCC patients should not be amenable to treatment with surgery or to orthotopic liver transplant (Phase I)
HCC patients only:\r\n* First line (i.e., no prior systemic therapy) or second-line (with prior first-line sorafenib therapy only) advanced HCC \r\n* Child Pugh class A or B7 liver disease \r\n* Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if >= 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable (Phase I)
HCC patients only: Cancer potentially amenable to local modalities of therapy or surgical resection (phase I)
Fibrolamellar histology HCC, mixed hepatocholangiocarcinoma, hepatic sarcomas and other non-HCC primary liver tumors
First line advanced HCC (i.e., no prior systemic therapy)
Patients must have histopathological confirmation of hepatocellular carcinoma (HCC) by the Laboratory of Pathology of the National Cancer Institute (NCI) prior to entering this study OR
Histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology, are highly suggestive of a diagnosis of HCC
Hepatocellular Carcinoma (HCC) --Histologic or cytologic diagnosis of hepatocellular carcinoma
HCC diagnosed by tissue or imaging study
Unresectable HCC without extrahepatic disease based on CT
No prior systemic therapy for HCC
Patients with hepatocellular carcinoma (HCC) are eligible for this trial; HCC is defined as having at least one of the following:\r\n* HCC diagnosed either on biopsy or based on standard imaging criteria on contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) (arterial enhancement with washout and pseudocapsule); or\r\n* A discrete hepatic tumor(s) as defined by the Barcelona criteria for cirrhotic patients, > 1 centimeter (cm) with arterial hypervascularity and venous or delayed phase washout on CT or MRI\r\n* Presentation at multidisciplinary liver tumor board to assess eligibility for either SBRT or MWA
Patients with 1 focus of HCC will be eligible if their tumor is 3.5 cm or less in greatest diameter; patients with 2 foci of HCC will be eligible if each lesion is 3.5 cm in diameter or less and the combined diameter of both lesions is 5 cm or less
The foci of HCC must be in an anatomic location amendable to treatment by both MWA and SBRT
Patients with 3 or more foci of HCC
Participation in qualitative interview during phase 1 (Dana-Farber Harvard Cancer Center [DF/HCC] 16-396)
Participants with advanced or metastatic and/or unresectable HCC
Histologic proof of HCC reviewed and confirmed per the local standard of care
A diagnosis of HCC based on histopathologic findings, or a diagnosis of cirrhosis and a tumor with classical HCC imaging characteristics.
Sorafenib was the only systemic therapy for HCC and was discontinued for disease progression or intolerance (Main Global and ME2 Cohorts only).
The participant received one prior systemic therapy regimen, excluding prior sorafenib, for the treatment of HCC (OLE Cohort only).
Only participants found to express high levels (immunohistochemistry [IHC] score 3 and above) of gamma-OHPdG (gamma-OHPdG-high hepatocellular carcinoma [HCC]) in baseline liver biopsy will be enrolled to receive Polyphenon E treatment
Participant has confirmed HCC by CT/MRI; participants who have previously had HCC but have been treated and have been recurrence free for 5 years are eligible
Patients with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, or metastatic liver cancer planned to receive definitive doses of radiation or surgical resection are eligible
Scheduled for TACE treatment of a hepatocellular carcinoma (HCC) mass (lesions reported as Liver Imaging Reporting and Data Systems 4B or 5 or Organ Procurement and Transplantation Network 5a or 5b)
Have an HCC mass viewable on grayscale B-mode ultrasound
Patients not eligible or scheduled for TACE of a HCC mass
Patients scheduled for 90Y radioembolization for HCC as part of their standard of care
Subjects must have a diagnosis of hepatocellular carcinoma (HCC) and a treatment plan to undergo radioembolization therapy with Y-90 at Indiana University Health Hospital
Patients with a known infiltrative variant of HCC
Patients diagnosed with HCC, who will undergo resection or transplantation within 6 months, as part of routine clinical care and patients diagnosed with unresectable HCC
Patients with unresectable HCC undergoing systemic therapy based on clinical indication or approved drug trial; and/or undergoing clinically indicated Y90 radioembolization
HCC PATIENTS: Patient with confirmed diagnosis of HCC, and untreated or
HCC PATIENTS: Patients with suspected HCC (suspected HCC nodules should preferably be smaller than 3 cm and preferably within 6 cm in depth of the transducer head to minimize attenuation) and untreated or
HCC PATIENTS: Patients at a higher risk of HCC undergoing a screening program by ultrasound
Liver tumor diagnosed histologically as HCC or suspected of being HCC in association with serum alpha-fetoprotein level > 200 or tumor mass with characteristics of malignancy on diagnostic imaging
Part 1: HCC; cholangiocarcinoma; or esophageal, nasopharyngeal, or serous ovarian cancer, regardless of FGF/FGFR status.
Cohort A: HCC with FGF19 amplification.
Cohort B: HCC without FGF19 amplification.
Histologically confirmed HCC, not amenable to transplant, resection or loco-regional therapy
Other active malignancy besides HCC within 3 years.
Must be listed for liver transplantation with HCC exception points based on the imaging diagnosis of at least one Organ Procurement and Transplantation Network (OPTN) class 5 HCC lesion(s) per study-defined imaging criteria (participating institutions may not enroll patients in whom the HCC diagnosis is solely based on biopsy and who do not have at least one liver lesion that meets imaging criteria for OPTN Stage 2, Class 5 HCC)\r\n* Patients must meet one of the following descriptions based on imaging findings:\r\n** EITHER OPTN Class 5B: at least 1 focal liver lesion(s) >= 2 cm diameter compatible with imaging diagnosis of Stage II HCC on contrast-enhanced CT imaging and/or contrast-enhanced MRI;\r\n** OR OPTN Class 5A: 2 or 3 focal liver lesions, each between > 1 and < 3 cm diameter, if each is compatible with imaging diagnosis of HCC on contrast-enhanced CT imaging and/or contrast-enhanced MRI\r\n** Imaging findings at the patient level in both situations must be within the United Network for Organ Sharing (UNOS) Stage 2, which is Milan criteria
Does not meet OPTN Class 5 imaging criteria for HCC, even if they have biopsy-proven HCC; NOTE: Patients enrolled to the trial under the “Declaration of Intent to List” mechanism who fail to be listed with HCC MELD/PELD Score Exception history data on the UNOS UNET Web site within 60 days from enrollment will come off trial and will not be counted towards target accrual
Subjects must have verified unresectable hepatocellular carcinoma (HCC), diagnosed on the basis of clinical and imaging criteria
Subjects must satisfy one of the following conditions pertaining to their eligibility to undergo orthotopic liver transplantation (OLT):\r\n* HCC that is within Milan Criteria, i.e., TACE is indicated as a “bridge” to OLT (Group I); or\r\n* HCC that is outside Milan Criteria, i.e., TACE is indicated as a means of “down-staging” into transplant eligibility (Group II)
Subjects who have received prior treatment for HCC (prior surgical procedures not related to HCC are allowed)
History of HCC or suspicious mass on imaging within 6 months prior to ascertainment of eligibility
HCC screening prior to randomization