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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Nerviano Medical Sciences S.r.l.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jan 2025 → 21 Apr 2026

Decision date (initial)

2024-12-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Nerviano Medical Sciences S.r.l.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Therapy, Pharmacokinetic

To determine the antitumor activity of NMS-01940153E administered with the immune checkpoint inhibitor (ICI) atezolizumab with (Part A, B) or without (Part C) low dose decitabine priming to adult patients with unresectable HCC previously treated with immune checkpoint inhibitors

Secondary objectives 3

1. To determine the safety and tolerability profile of NMS-01940153E admnistered with the ICI atezolizumab with (Part A, B) or without (Part C) low dose decitabine priming to adult patients with unresectable HCC previously treated with immune checkpoint inhibitors
2. To assess additional clinical outcome measures of antitumoral activity of NMS-01940153E administered with the ICI atezolizumab with (Part A, B) or without (Part C) low dose decitabine priming based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
3. To evaluate the pharmacokinetics (PK) of NMS-01940153E and its main metabolite NMS-03593478 in plasma, co-administered with the ICI atezolizumab

Conditions and MedDRA coding

Unresectable Hepatocellular Carcinoma (HCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. 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.
2. 2. 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).
3. 3. 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.
4. 4. Had received only one line of prior treatment including atezolizumab plus bevacizumab or other approved check-point inhibitor (ICI) combination as 1st line.
5. 5. 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.
6. 6. Patients must have confirmation of radiological progression on prior ICI treatment before inclusion.
7. 7. Barcelona Clinic Liver Cancer stage B (that is not eligible for locoregional therapy) or stage C.
8. 8. Eastern Cooperative Oncology Group performance status of 0 or 1.
9. 9. Child-Pugh score of A within 7 days prior to enrollment.
10. 10. Aged ≥18 years old on day of consent.

Exclusion criteria 8

1. 1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed hepatocholangiocarcinoma.
2. 2. 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.
3. 3. 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.
4. 4. Ascites defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2.
5. 5. 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).
6. 6. Recent history of hepatic encephalopathy Grade ≥2.
7. 7. Patients with prior administration of a tyrosine kinase inhibitor (TKI) in advanced disease.
8. 8. Patients with previous episodes (minimum of 1 episode) of neutropenia grade 3 and 4 related to therapeutic treatment for HCC.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR, calculated as the proportion of evaluable patients who have achieved, as BOR, confirmed CR or PR measured by investigator-assessed RECIST 1.1.

Secondary endpoints 5

1. Overall safety profile characterized by type, severity (graded using National Cancer Institute CTCAE version 5.0), duration of the adverse events (AEs), laboratory, and electrocardiogram abnormalities, unacceptable toxicities, and relationship of the AEs to study treatment in the first and subsequent cycles of therapy
2. Duration of response (DOR) as measured by investigator-assessed RECIST 1.1
3. Progression-free survival (PFS), including landmark analyses, as measured by investigator-assessed RECIST 1.1
4. Overall survival
5. Pharmacokinetic parameters of NMS-01940153E and its main metabolite NMS-03593478 in plasma.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Nerviano Medical Sciences S.r.l.

Sponsor organisation

Nerviano Medical Sciences S.r.l.

Address

Via Louis Pasteur 10

City

Nerviano

Postcode

20014

Country

Italy

Scientific contact point

Organisation

Nerviano Medical Sciences S.r.l.

Contact name

Global Clinical Lead

Public contact point

Organisation

Nerviano Medical Sciences S.r.l.

Contact name

Global Clinical Lead

Third parties 4

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications