A trial to learn how well NMS-01940153E works in combination with atezolizumab and priming administration of decitabine or with atezolizumab alone in patients with hepatocellular carcinoma (HCC) that cannot be removed by surgery and who received prior treatment with other anti-cancer medicines

Prior treatment

• Previous history or actual presence of varices, unless this medical condition is stable with optimal medical management (eg, non-selective beta blocker, proton pump inhibitor) and there is no active or a prior documented gastrointestinal bleeding episode (eg, esophageal varices or ulcer bleeding) within the last 12 months.
• Patients with prior administration of a tyrosine kinase inhibitor (TKI) in advanced disease.
• Patients with previous episodes (minimum of 1 episode) of neutropenia grade 3 and 4 related to therapeutic treatment for HCC.

Other illness

• Ascites defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2.
• Recent history of hepatic encephalopathy Grade ≥2.

Lab values

• QT interval corrected by Fridericia ≥480 ms or with risk factors for Torsade de Pointes (eg, heart failure, uncontrolled hypokalemia, family history of long QT syndrome) or receiving treatment with concomitant medications known to prolong the QT/corrected QT interval that cannot be replaced with another treatment.

Other

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed hepatocholangiocarcinoma.
• Uncontrolled high blood pressure (systolic blood pressure >150 mmHg and/or diastolic blood pressure >95 mmHg, despite optimal treatment, on at least 2 out of 3 determinations repeated at 30 minute intervals and done in case that the first 1 meets the criterion for exclusion).

• Histological, cytological, or radiological diagnosis of HCC, according to the American Association for the Study of Liver Diseases/European Association for the Study of the Liver criteria.
• Aged ≥18 years old on day of consent.
• Disease that is not amenable to a curative treatment approach (eg, transplant, surgery, radiofrequency ablation) and unsuitable for or refractory to locoregional treatments (eg, transarterial chemoembolization).
• At least 1 unidimensional measurable lesion by computed tomography, positron emission tomography, or magnetic resonance imaging according to RECIST 1.1 which is either not previously treated by local therapy or, if treated, it has clearly progressed before the patient is recruited.
• Had received only one line of prior treatment including atezolizumab plus bevacizumab or other approved check-point inhibitor (ICI) combination as 1st line.
• Patients treated with the prior ICI must have received at least 4 consecutive treatment cycles, and 2 subsequent tumor assessments. It is required that at least 1 tumor assessment showed either stable disease (SD), partial response (PR), or complete response (CR) while on treatment with prior ICI.
• Patients must have confirmation of radiological progression on prior ICI treatment before inclusion.
• Barcelona Clinic Liver Cancer stage B (that is not eligible for locoregional therapy) or stage C.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Child-Pugh score of A within 7 days prior to enrollment.