Study on Safety and Efficacy of NMS-01940153E in Adult Patients With Unresectable Hepatocellular Carcinoma (HCC) Previously Treated With Systemic Therapy

NCT05630937 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: MPSA-153-0012020-001002-26
• Study Type: interventional
• Target: 31
• Locations: 3 countries
• Sites: 9

Brief 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. 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.

Conditions

Unresectable Hepatocellular Carcinoma (HCC)

Keywords

Unresectable Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  Phase II: From Phase II start to Study Completion (23 months)

Secondary Outcomes (21)

• Treatment-emergent Adverse Events by Maximum CTC Grade

  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

  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

  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

  From screening to 28 days follow-up, an average 6 months

• Blood Chemistry: Treatment-emergent Abnormalities by Dose Level

  From screening to 28 days follow-up, an average 6 months

Study Arms (1)

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.

Drug: NMS-01940153E

Interventions

NMS-01940153E DRUG

Route of administration: intravenous (IV) solution

NMS-01940153E

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Nerviano Medical Sciences: lead

Study Sites (9)

University of California Irvine Health

Orange, California, 92868-3201, United States

Location

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, 63110-1032, United States

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Sanitaria Locale Napoli 1 Centro - Ospedale del Mare

Naples, 80145, Italy

Location

Istituto Oncologico Veneto - IRCCS

Padua, 35128, Italy

Location

Azienda Ospedaliero Universitaria Pisana - Ospedale Santa Chiara

Pisa, 56126, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Azienda Ospedaliera Ordine Mauriziano di Torino

Torino, 10128, Italy

Location

Hospital Clínic de Barcelona

Barcelona, 8036, Spain

Location

Limitations and Caveats

In the Phase II part of the study, among the patients evaluable for efficacy, no objective response (partial response or clinical response) was observed at the first futility analysis. Therefore, this study was terminated for clinical futility, according to the protocol rules.

Results Point of Contact

• Title: Alberto Ocana
• Organization: Nerviano Medical Sciences S.r.l.

DL-Clinicaltrials@nervianoms.com

39 0331 58 1111

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2022
• First Posted: November 30, 2022
• Study Start: November 13, 2020
• Primary Completion: January 31, 2024
• Study Completion: August 6, 2024
• Last Updated: June 19, 2025
• Results First Posted: May 7, 2025

Record last verified: 2025-06

Locations

IT (6); ES (1); US (2)