Unresectable Hepatocellular Carcinoma (HCC)Phase 1/2NCT05630937
Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy
A Phase 1/2 study testing NMS-01940153E in people with Unresectable Hepatocellular Carcinoma (HCC), run by Nerviano Medical Sciences at 9 sites in 3 countries.
Trial summary
This is a Phase I/II, open-label, non-randomized, multicenter study to explore safety, tolerability and antitumor activity of NMS-01940153E as single agent in adult patients with unresectable hepatocellular carcinoma (HCC) previously treated with systemic therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma (HCC)
- What is being tested?
- NMS-01940153E
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 9 sitesin 3 countries
- Study dates
- 13 Nov 2020to 6 Aug 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Histological, cytological or radiological diagnosis of HCC, according to the American Association for the Study of Liver Diseases (AASLD) / European Association for the Study of the Liver (EASL) criteria, in subjects that are refractory or not able to tolerate the standard therapy, or subjects for whom the standard therapy is not considered appropriate by the physician.
- The subject has disease that is not amenable to a curative treatment approach (e.g., transplant, surgery, radiofrequency ablation) and unsuitable for or refractory to locoregional treatments (e.g., TACE).
- At least one uni-dimensional measurable lesion by CT or MRI according to RECIST 1.1 which is either not previously treated by local therapy or, if treated, it has clearly progressed before the subject is recruited.
- Phase I only: subjects must have disease relapsed or refractory to the standard of care treatment not exceeding 3 lines of prior systemic treatment. Subjects intolerant to previous treatment with tyrosine kinase inhibitors (TKIs) are eligible. Phase II: subjects must have disease relapsed or refractory to the standard of care treatment including an immunocheckpoint inhibitor as first line and at least a tyrosine kinase inhibitor, not exceeding 3 lines of prior systemic treatment. A minimum of 14 days of treatment with prior TKI would be required to qualify as line of therapy;
- Child-Pugh score ≤ 6 (class A).
Show all 15Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Age ≥18 years old on day of consent.
- No history of liver transplantation or not listed for high urgent transplantation.
- Meets required laboratory data
- In case of active hepatitis B (HBV) or chronic HIV infection the patient should receive antiviral therapy per local standard of care.
- Patients must use effective contraception or abstinence. Female subjects must be surgically sterile or, if subjects of childbearing potential, must agree to use effective contraception or abstinence during the period of therapy and in the following 180 days after discontinuation of study treatment. Male subjects must be surgically sterile or must agree to use effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment.
- With the exception of alopecia, resolution of all acute toxic effects of any prior systemic therapy, surgery or radiotherapy to National Cancer Institute (NCI) common terminology criteria (CTC) (Version 5.0) Grade ≤1 or to the baseline laboratory values as defined in Inclusion Criterion Number 9.
- Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol.
- Signed and dated independent ethics committee (IEC)-approved Informed Consent Form indicating that the subject is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the investigational nature of the therapy, potential benefits, side effects, discomforts, risks and alternative treatments.
Who cannot join
- The presence of any of the following will exclude a subject from study enrollment:
- Known fibrolamellar HCC or mixed hepato-cholangiocarcinoma.
- Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
- Subjects with QT interval using Fridericia standard (QTcF) ≥480 milliseconds or with risk factors for torsade de pointes (e.g., heart failure, uncontrolled hypokalemia, family history of long QT syndrome) or receiving treatment with concomitant medications known to prolong the QT/QTc interval that cannot be replaced with another treatment.
- Ascites defined as CTCAE Grade ≥2. Subjects who have been on a stable medication regimen for at least 2 months to manage ascites are eligible if they show ascites Grade <2.
- Subjects with clinically undetectable ascites who are Child A with detectable ascites at CT/MRI are eligible.
Show all 26Show fewer
- Uncontrolled high blood pressure (systolic blood pressure, SBP >150 mmHg and/or diastolic blood pressure, DBP >95 mmHg, despite optimal treatment, on at least 2 out of 3 determinations repeated at 30 minutes interval and done in case that the first one meets the criterion for exclusion).
- Direct-Acting Antivirals (DAA) at the time of treatment start; previous hepatitis C virus (HCV) treatment with DAAs is allowed.
- Clinical evidence of hepatic encephalopathy.
- Known brain metastases or evidence of leptomeningeal disease.
- Known history of allergic reactions to polysorbate 80.
- Any of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis (except chronic/stable portal vein thrombosis).
- Major surgery, other than diagnostic surgery, within 4 weeks before treatment start.
- Any anticancer agent within 4 weeks or, in absence of toxicity, 5 half-lives (within 6 weeks for nitrosureas, mitomycin C and liposomal doxorubicin) before treatment start.
- Radiation therapy within 4 weeks or radionuclide treatment (e.g., I-131 or Y-90) within 6 weeks before treatment start.
- Untreated uncontrolled bacterial, viral, or fungal infections including acute HIV infection or acquired immunodeficiency syndrome (AIDS), untreated uncontrolled HBV, untreated uncontrolled HCV, untreated uncontrolled concomitant HBV and HCV; patients who are seropositive following HBV vaccine are eligible.
- Subjects under treatment with therapeutic dose of anticoagulants (e.g., warfarin or warfarin-related agents, low-molecular weight heparin, or similar agent such as anti Xa and anti-thrombin agents) or antiplatelet agents (e.g. clopidogrel) or with coagulation disorders. Aspirin at dose up to 100 mg is permitted. Prophylaxis with anticoagulants is allowed to meet the international normalized ratio (INR) value range as cited in inclusion criterion 9.
- Uncontrolled diabetes mellitus.
- Pregnant or breast-feeding women.
- Known second malignancy that is progressing or requiring active treatment. Exceptions include adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri.
- Current enrollment or participation in another interventional clinical trial.
- Clinically significant respiratory or metabolic diseases uncontrolled by medication.
- Subjects with active alcohol and/or substances abuse.
- Any known organ dysfunction, serious illness, acute or chronic medical or psychiatric condition, or laboratory abnormality which, in the Investigator's opinion, may increase the risk associated/interfere with study participation, or with the interpretation of the results.
- Subjects who, within 7 days prior to the first NMS-01940153E intake, are receiving or received strong inducers of flavin-containing monooxygenase FMO1 and FMO3.
- Subjects who are receiving sensitive CYP3A4 substrates, CYP3A4 and breast cancer resistance protein (BCRP) substrates with narrow therapeutic index (NTI).
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
Italy6 sites
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Azienda Sanitaria Locale Napoli 1 Centro - Ospedale del Mare
Naples, 80145
Istituto Oncologico Veneto - IRCCS
Padova, 35128
Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara
Pisa, 56126
Istituto Clinico Humanitas
Rozzano, 20089
Azienda Ospedaliera Ordine Mauriziano di Torino
Torino, 10128
United States2 sites
University of California Irvine Health
Orange, California, 92868-3201
Siteman Cancer Center - Washington University Medical Campus
St Louis, Missouri, 63110-1032
About this study
Official title: Phase I/II Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy
This is a Phase I/II, open-label, non-randomized, multicenter study to explore safety, tolerability and antitumor activity of NMS-01940153E as single agent in adult patients with unresectable hepatocellular carcinoma (HCC) previously treated with systemic therapy.
The Phase I portion is designed as a dose-escalation study in sequential cohorts of patients aimed to obtain the maximum tolerated dose (MTD) that is defined based on the dose limiting toxicities (DLTs) observed in the first cycle of treatment.
The Phase II portion is designed as a two-stage study with an interim analysis for futility and stopping criteria for unacceptable toxicity to assess the antitumor activity of NMS-01940153E in adult patients with unresectable HCC previously treated with systemic therapy measured as objective response rate.
- Being tested
- NMS-01940153E
- Keywords
- Unresectable Hepatocellular Carcinoma (HCC)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMS-01940153EDrug
Route of administration: intravenous (IV) solution
| Study group | Role | What they receive |
|---|---|---|
| NMS-01940153E | Experimental | Phase I: Patients will be allocated to sequential cohorts of progressively higher dose levels of NMS-01940153E based on the presence of Dose Limiting Toxicities (DLT).
Phase II: Patients will be treated at the recommended Phase II dose (RP2D) defined in the Phase I portion. Receives: Drug: NMS-01940153E |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I Drug Related Dose Limiting Toxicities (DLTs)
All 12 Phase I treated patients were evaluable for DLT (Dose-Limiting Toxicity Evaluable Set) and included 6 patients treated at each of the two dose levels explored (i.e., 100 mg/m2/week and 135 mg/m2/week) who received at least 66% of the study drug in the first 28-day cycle of treatment and underwent a DLT assessment within the DLT window.
Participants who experienced DLTs are presented.
Measured: Phase I: From screening to end of first 28-day cycle (17 months)
Phase II Objective Response Rate
The objective response rate (ORR) was calculated as the proportion of evaluable patients who achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) measured by investigator-assessed RECIST 1.1 (Phase II).
Measured: Phase II: From Phase II start to Study Completion (23 months)
Secondary outcomes (21)
Treatment-emergent Adverse Events by Maximum CTC Grade
The maximum Common Terminology Criteria (CTC) grade (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed.
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.
Grade 4 Life-threatening consequences; urgent intervention indicated.
Measured: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Treatment-emergent Adverse Events Related to NMS-01940153E
The number of treatment-emergent adverse events related to NMS-01940153E by maximum CTC grade experienced (graded using NCI CTCAE Version 5.0). Whether the the AE was related or not was assessed by the investigator. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented.
Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.
Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living.
Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living.
Grade 4 Life-threatening. Phase 2 started before Phase 1 completed.
Measured: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade
Number of treatment emergent abnormalities (at any grade) at all dose levels are presented.
CTC = Common Terminology Criteria WBC = white blood cells
Measured: From screening to 28 days follow-up, an average 6 months
Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1
The mean days to first occurrence of neutrophil count decrease are presented for all dose levels.
Grade 0: ≥2,000/mm3 Grade 1: ≥1,500-< 2,000/mm3 Grade 2: ≥1,000- < 1,500/mm3 Grade 3: ≥500- < 1,000/mm3 Grade 4: <500/mm3
- G3 = Time (days) to Treatment Start to First Occurrence of Neutrophil Count Decrease >=Grade 3
- G3 to Recovery to G1 = Time (days) to First Occurrence of Neutrophil Count Decrease >= Grade 3 to Recovery to Grade 1
Measured: From screening to 28 days follow-up, an average 6 months
Blood Chemistry: Treatment-emergent Abnormalities by Dose Level
Treatment-emergent abnormalities in blood chemistry at any grade are presented by dose level.
ALP = Alkaline phosphatase ALT = Alanine aminotransferase AST = Aspartate aminotransferase GGT = Gamma-glutamyl transferase LDH = Lactate dehydrogenase
Measured: From screening to 28 days follow-up, an average 6 months
Blood Chemistry and Coagulation: Treatment-emergent Abnormalities
Treatment Emergent abnormalities by dose Level are presented for blood chemistry and coagulation parameters.
INR = international normalized ratio LNL = lower normal limit NL = normal limit ULN = upper limit of normal
Measured: From screening to 28 days follow-up, an average 6 months
Electrocardiogram Abnormalities
The number of participants who experienced electrocardiogram abnormalities are presented.
Measured: From screening to 28 days follow-up, an average 6 months
Tmax and Tlast of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion.
Tmax = Time to maximum observed plasma concentration Tlast = Time of last detectable concentration
Measured: Day 1 to Day 15
Cmax and Clast of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion.
Cmax = Maximum observed plasma concentration Clast = Last detectable concentration
Measured: Day 1 to Day 15
AUClast, AUCweekly, and AUCinf of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15.
AUClast = Area under the interpolated observed plasma time-concentration curve from infusion start to the last observed plasma concentration AUCweekly = Area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours AUCinf = Area under the interpolated observed plasma time-concentration curve from infusion start extrapolated to infinity based on the last observed plasma concentration
Measured: From Days 1 to 21 (168 hours after the Day 15 infusion)
t½,z of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion.
t½,z = Half-life of the terminal phase of observed plasma concentration
Measured: Day 1 to Day 15
CL and CLss of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion.
CL = Clearance based on last observed concentration and extrapolation to infinity CLss = Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state
Measured: Day 1 to Day 15
Vss and Vss,SS of NMS-01940153E
Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion.
Vss = Volume of distribution at steady state based last observed concentration extrapolated to infinity and Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state Vss,SS = Volume of distribution at steady state based last observed concentration extrapolated to infinity and clearance based on last observed concentration and extrapolation to infinity
Measured: Day 1 to Day 15
RA AUCweekly and RA Cmax of NMS-01940153E
Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15.
RA AUCweekly = Accumulation ratio Day 1 to 15 calculated using area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours RA Cmax = Accumulation ratio Day 1 to 15 calculated using maximum observed plasma concentration
Measured: Day 21 (168 hours after the Day 15 infusion)
FE of NMS-01940153E
Urine pharmacokinetic profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion.
FE = Molar fraction of excreted compound relative to the administered molar dose calculated using urine concentration and volume data
Measured: Day 1 to Day 15
Phase I Objective Tumor Response (Partial and Complete Response)
Phase I any dose level, objective response and best overall tumor response are presented, as measured by investigator assessed RECIST 1.1 (Phase I).
The objective response rate was calculated as the proportion of evaluable patients who achieved best overall response (BOR), confirmed complete response (CR) or partial response (PR).
Measured: Phase I: From the Study Start Date to Phase I Completion (32 months)
Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST
Objective response rate as measured by investigator-assessed mRECIST in Phase II.
Measured: Phase II: From Phase II start to Study Completion (23 months)
Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1
Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1.
Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response.
Measured: Phase I: From the Study Start Date to Phase I Completion (32 months)
Phase II: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1. and Investigator-assessed mRECIST
Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1 and investigator-assessed modified RECIST (mRECIST).
Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response.
Measured: Phase II: From Phase II start to Study Completion (23 months)
Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II
Progression Free Survival as measured by investigator assessed RECIST 1.1, for all treated participants in Phase I and Phase II.
Phase 2 started before Phase 1 completed.
Measured: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Overall Survival in Phases I and II
Overall Survival for all treated participants in Phases I and II. The estimates are based on the Kaplan-Meier (KM) method.
Phase 2 started before Phase 1 completed.
Measured: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2022
- Study start13 Nov 2020
- Primary completion31 Jan 2024
- Study completion6 Aug 2024
Why it stopped: In the Phase II part of the study, among the participants evaluable for efficacy, no objective (partial response or clinical response) was observed at the first futility analysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Unresectable Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nerviano Medical Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05630937
- Sponsor's protocol ID
- MPSA-153-001
- Other IDs
- 2020-001002-26
- Status last verified
- Jun 2025
- First submitted
- 18 Nov 2022
- Last updated
- 19 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy
- ClinicalTrials.gov ID
- NCT05630937
- Acronym / sponsor ID
- MPSA-153-001
- Keywords
- Unresectable Hepatocellular Carcinoma (HCC)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: In the Phase II part of the study, among the participants evaluable for efficacy, no objective (partial response or clinical response) was observed at the first futility analysis.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Nerviano Medical SciencesIndustry (pharma, biotech, devices)
- Study start
- 13 Nov 2020 (actual)
- Primary completion
- 31 Jan 2024 (actual)
- Study completion
- 6 Aug 2024 (actual)
- First posted
- 30 Nov 2022 (actual)
- Results
- Posted 7 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase I/II, open-label, non-randomized, multicenter study to explore safety, tolerability and antitumor activity of NMS-01940153E as single agent in adult patients with unresectable hepatocellular carcinoma (HCC) previously treated with systemic therapy.
The Phase I portion is designed as a dose-escalation study in sequential cohorts of patients aimed to obtain the maximum tolerated dose (MTD) that is defined based on the dose limiting toxicities (DLTs) observed in the first cycle of treatment.
The Phase II portion is designed as a two-stage study with an interim analysis for futility and stopping criteria for unacceptable toxicity to assess the antitumor activity of NMS-01940153E in adult patients with unresectable HCC previously treated with systemic therapy measured as objective response rate.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NMS-01940153E | Experimental | Drug: NMS-01940153EPhase I: Patients will be allocated to sequential cohorts of progressively higher dose levels of NMS-01940153E based on the presence of Dose Limiting Toxicities (DLT). Phase II: Patients will be treated at the recommended Phase II dose (RP2D) defined in the Phase I portion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
- Histological, cytological or radiological diagnosis of HCC, according to the American Association for the Study of Liver Diseases (AASLD) / European Association for the Study of the Liver (EASL) criteria, in subjects that are refractory or not able to tolerate the standard therapy, or subjects for whom the standard therapy is not considered appropriate by the physician.
- The subject has disease that is not amenable to a curative treatment approach (e.g., transplant, surgery, radiofrequency ablation) and unsuitable for or refractory to locoregional treatments (e.g., TACE).
- At least one uni-dimensional measurable lesion by CT or MRI according to RECIST 1.1 which is either not previously treated by local therapy or, if treated, it has clearly progressed before the subject is recruited.
- Phase I only: subjects must have disease relapsed or refractory to the standard of care treatment not exceeding 3 lines of prior systemic treatment. Subjects intolerant to previous treatment with tyrosine kinase inhibitors (TKIs) are eligible. Phase II: subjects must have disease relapsed or refractory to the standard of care treatment including an immunocheckpoint inhibitor as first line and at least a tyrosine kinase inhibitor, not exceeding 3 lines of prior systemic treatment. A minimum of 14 days of treatment with prior TKI would be required to qualify as line of therapy;
Key exclusion criteria (26 listed)
- Known fibrolamellar HCC or mixed hepato-cholangiocarcinoma.
- Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry.
- Subjects with QT interval using Fridericia standard (QTcF) ≥480 milliseconds or with risk factors for torsade de pointes (e.g., heart failure, uncontrolled hypokalemia, family history of long QT syndrome) or receiving treatment with concomitant medications known to prolong the QT/QTc interval that cannot be replaced with another treatment.
- Ascites defined as CTCAE Grade ≥2. Subjects who have been on a stable medication regimen for at least 2 months to manage ascites are eligible if they show ascites Grade <2.
- Subjects with clinically undetectable ascites who are Child A with detectable ascites at CT/MRI are eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NMS-01940153ERoute of administration: intravenous (IV) solution | Drug | NMS-01940153E |
Primary outcome
Phase I Drug Related Dose Limiting Toxicities (DLTs)
Time frame: Phase I: From screening to end of first 28-day cycle (17 months)
All 12 Phase I treated patients were evaluable for DLT (Dose-Limiting Toxicity Evaluable Set) and included 6 patients treated at each of the two dose levels explored (i.e., 100 mg/m2/week and 135 mg/m2/week) who received at least 66% of the study drug in the first 28-day cycle of treatment and underwent a DLT assessment within the DLT window. Participants who experienced DLTs are presented.
Phase II Objective Response Rate
Time frame: Phase II: From Phase II start to Study Completion (23 months)
The objective response rate (ORR) was calculated as the proportion of evaluable patients who achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) measured by investigator-assessed RECIST 1.1 (Phase II).
21 secondary outcomes
Treatment-emergent Adverse Events by Maximum CTC Grade
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Treatment-emergent Adverse Events Related to NMS-01940153E
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade
Time frame: From screening to 28 days follow-up, an average 6 months
Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1
Time frame: From screening to 28 days follow-up, an average 6 months
Blood Chemistry: Treatment-emergent Abnormalities by Dose Level
Time frame: From screening to 28 days follow-up, an average 6 months
Blood Chemistry and Coagulation: Treatment-emergent Abnormalities
Time frame: From screening to 28 days follow-up, an average 6 months
Electrocardiogram Abnormalities
Time frame: From screening to 28 days follow-up, an average 6 months
Tmax and Tlast of NMS-01940153E
Time frame: Day 1 to Day 15
Cmax and Clast of NMS-01940153E
Time frame: Day 1 to Day 15
AUClast, AUCweekly, and AUCinf of NMS-01940153E
Time frame: From Days 1 to 21 (168 hours after the Day 15 infusion)
t½,z of NMS-01940153E
Time frame: Day 1 to Day 15
CL and CLss of NMS-01940153E
Time frame: Day 1 to Day 15
Vss and Vss,SS of NMS-01940153E
Time frame: Day 1 to Day 15
RA AUCweekly and RA Cmax of NMS-01940153E
Time frame: Day 21 (168 hours after the Day 15 infusion)
FE of NMS-01940153E
Time frame: Day 1 to Day 15
Phase I Objective Tumor Response (Partial and Complete Response)
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months)
Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST
Time frame: Phase II: From Phase II start to Study Completion (23 months)
Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months)
Phase II: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1. and Investigator-assessed mRECIST
Time frame: Phase II: From Phase II start to Study Completion (23 months)
Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Overall Survival in Phases I and II
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Unresectable Hepatocellular Carcinoma (HCC)
Not yet recruitingPhase 2
PEARL Trial: Partial TACE Enhancing Anti-tumor Response With Lenvatinib in Unresectable HCC
Hepatocellular Carcinoma
Active, not recruitingPhase 3
Radiation Therapy With Protons or Photons in Treating Patients With Liver Cancer
Recurrent Hepatocellular Carcinoma, Stage III Hepatocellular Carcinoma AJCC v7
Active, not recruitingPhase 1/2
Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer
Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8
Not yet recruitingObservational study
Immune-Related Adverse Events and Clinical Outcomes of First-Line Immunotherapy in Egyptian Patients With Unresectable Hepatocellular Carcinoma
Hepatocellular Carcinoma, Hepatocellular Carcinoma (HCC)
Active, not recruiting
BioPearl™ Microspheres Loaded With Doxorubicin for the Treatment of Unresectable Hepatocellular Carcinoma (HCC)
Hepatocellular Carcinoma Non-resectable
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NMS-01940153E in people with Unresectable Hepatocellular Carcinoma (HCC), run by Nerviano Medical Sciences at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy, United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I Drug Related Dose Limiting Toxicities (DLTs) (time frame: Phase I: From screening to end of first 28-day cycle (17 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2025.