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NCT05630937

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

Terminated Phase 1, PHASE2 Results posted Last updated 19 June 2025
What this trial tests

Phase 1, PHASE2 trial testing NMS-01940153E in Unresectable Hepatocellular Carcinoma (HCC) in 31 participants. Terminated before completion.

Timeline
13 November 2020
Primary endpoint
31 January 2024
6 August 2024

Quick facts

Lead sponsorNerviano Medical Sciences
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationna
Designsequential
Maskingnone
Primary purposetreatment
Enrollment31
Start date13 November 2020
Primary completion31 January 2024
Estimated completion6 August 2024
Sites9 locations across Italy, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Nerviano Medical Sciences — full company profile →

Who can join

18 and older, any sex, with Unresectable Hepatocellular Carcinoma (HCC). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase I Drug Related Dose Limiting Toxicities (DLTs) Primary · 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.

GroupValue95% CI
100 mg/m2/Week Dose (Phase I)0
135 mg/m2/Week Dose (Phase I)2
Phase II Objective Response Rate Primary · 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).

Stable Disease
GroupValue95% CI
Phase II (Evaluable Population)3
Progressive Disease
GroupValue95% CI
Phase II (Evaluable Population)11
Complete Response
GroupValue95% CI
Phase II (Evaluable Population)0
Partial Response
GroupValue95% CI
Phase II (Evaluable Population)0
Treatment-emergent Adverse Events by Maximum CTC Grade Secondary · Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)

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 acti

Grade 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)0
135 mg/m2/Week Dose (Phase I)0
Phase II (Evaluable Population)3
Grade 2
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)1
135 mg/m2/Week Dose (Phase I)1
Phase II (Evaluable Population)8
Grade 3
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)3
135 mg/m2/Week Dose (Phase I)3
Phase II (Evaluable Population)7
Grade 4
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)1
135 mg/m2/Week Dose (Phase I)2
Phase II (Evaluable Population)0
Treatment-emergent Adverse Events Related to NMS-01940153E Secondary · Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)

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 med

Grade 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)0
135 mg/m2/Week Dose (Phase I)0
Phase II (Evaluable Population)7
Grade 2
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)1
135 mg/m2/Week Dose (Phase I)1
Phase II (Evaluable Population)3
Grade 3
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)2
135 mg/m2/Week Dose (Phase I)2
Phase II (Evaluable Population)2
Grade 4
GroupValue95% CI
100 mg/m2/Week Dose (Phase I)1
135 mg/m2/Week Dose (Phase I)2
Phase II (Evaluable Population)0
Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade Secondary · From screening to 28 days follow-up, an average 6 months

Number of treatment emergent abnormalities (at any grade) at all dose levels are presented. CTC = Common Terminology Criteria WBC = white blood cells

Hemoglobin Decreased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)13
135 mg/m2/Week Dose (Phase I Only)5
All Treated Participants (Phase I and II; All Dose Levels)18
Neutrophil Count Decreased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)6
135 mg/m2/Week Dose (Phase I Only)4
All Treated Participants (Phase I and II; All Dose Levels)10
WBC Decreased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)8
135 mg/m2/Week Dose (Phase I Only)6
All Treated Participants (Phase I and II; All Dose Levels)14
Platelet Count Decreased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)6
135 mg/m2/Week Dose (Phase I Only)4
All Treated Participants (Phase I and II; All Dose Levels)10
Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 Secondary · From screening to 28 days follow-up, an average 6 months

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

>=G3
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)63.00± 19.80
135 mg/m2/Week Dose (Phase I Only)28.00± 15.36
All Treated Participants (Phase I and II; All Dose Levels)39.67± 23.38
>= G3 to Recovery to G1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)7.00± 1.41
135 mg/m2/Week Dose (Phase I Only)7.33± 3.51
All Treated Participants (Phase I and II; All Dose Levels)7.20± 2.59
Blood Chemistry: Treatment-emergent Abnormalities by Dose Level Secondary · From screening to 28 days follow-up, an average 6 months

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

Hypoalbuminemia
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)8
135 mg/m2/Week Dose (Phase I Only)4
All Treated Participants (Phase I and II; All Dose Levels)12
Hypoglycemia
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)0
135 mg/m2/Week Dose (Phase I Only)1
All Treated Participants (Phase I and II; All Dose Levels)1
AST Increased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)12
135 mg/m2/Week Dose (Phase I Only)3
All Treated Participants (Phase I and II; All Dose Levels)15
ALT Increased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)8
135 mg/m2/Week Dose (Phase I Only)2
All Treated Participants (Phase I and II; All Dose Levels)10
GGT Increased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)9
135 mg/m2/Week Dose (Phase I Only)1
All Treated Participants (Phase I and II; All Dose Levels)10
Creatinine Increased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)6
135 mg/m2/Week Dose (Phase I Only)3
All Treated Participants (Phase I and II; All Dose Levels)9
Blood Bilirubin Increased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)7
135 mg/m2/Week Dose (Phase I Only)1
All Treated Participants (Phase I and II; All Dose Levels)8
ALP Increased
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)10
135 mg/m2/Week Dose (Phase I Only)1
All Treated Participants (Phase I and II; All Dose Levels)11
Blood Chemistry and Coagulation: Treatment-emergent Abnormalities Secondary · From screening to 28 days follow-up, an average 6 months

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

Hyponatremia: Total
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)4
135 mg/m2/Week Dose (Phase I Only)2
All Treated Participants (Phase I and II; All Dose Levels)6
Hyponatremia: Below LNL
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)4
135 mg/m2/Week Dose (Phase I Only)2
All Treated Participants (Phase I and II; All Dose Levels)6
Hypokalemia: Total
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)0
135 mg/m2/Week Dose (Phase I Only)1
All Treated Participants (Phase I and II; All Dose Levels)1
Hypokalemia: Below LNL
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)0
135 mg/m2/Week Dose (Phase I Only)1
All Treated Participants (Phase I and II; All Dose Levels)1
Phosphatemia: Total
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)11
135 mg/m2/Week Dose (Phase I Only)2
All Treated Participants (Phase I and II; All Dose Levels)13
Phosphatemia: Above ULN
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)3
135 mg/m2/Week Dose (Phase I Only)0
All Treated Participants (Phase I and II; All Dose Levels)3
Phosphatemia: Below LNL
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)7
135 mg/m2/Week Dose (Phase I Only)2
All Treated Participants (Phase I and II; All Dose Levels)9
Phosphatemia: Above/Below NL
GroupValue95% CI
100 mg/m2/Week Dose (Phase I and II)1
135 mg/m2/Week Dose (Phase I Only)0
All Treated Participants (Phase I and II; All Dose Levels)1
Electrocardiogram Abnormalities Secondary · From screening to 28 days follow-up, an average 6 months

The number of participants who experienced electrocardiogram abnormalities are presented.

GroupValue95% CI
100 mg/m2/Week Dose (Phase I)0
135 mg/m2/Week Dose (Phase I)0
Phase II (Evaluable Population)0
Tmax and Tlast of NMS-01940153E Secondary · Day 1 to Day 15

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

Tmax: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)0.933± 0.0327
135 mg/m2/Week Dose (Phase I Only)1.19± 0.513
Tmax: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)1.10± 0.216
135 mg/m2/Week Dose (Phase I Only)1.87± 1.90
Tlast: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)169± 3.01
135 mg/m2/Week Dose (Phase I Only)154± 39.2
Tlast: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)144± 48.5
135 mg/m2/Week Dose (Phase I Only)169± 0.418
Cmax and Clast of NMS-01940153E Secondary · Day 1 to Day 15

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

Cmax: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)0.754± 0.174
135 mg/m2/Week Dose (Phase I Only)1.91± 0.640
Cmax: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)1.35± 1.10
135 mg/m2/Week Dose (Phase I Only)1.59± 1.31
Clast: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)0.0590± 0.0191
135 mg/m2/Week Dose (Phase I Only)0.0840± 0.0335
Clast: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)0.113± 0.0454
135 mg/m2/Week Dose (Phase I Only)0.133± 0.0779
AUClast, AUCweekly, and AUCinf of NMS-01940153E Secondary · From Days 1 to 21 (168 hours after the Day 15 infusion)

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

AUClast: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)20.8± 4.31
135 mg/m2/Week Dose (Phase I Only)24.8± 8.55
AUClast: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)30.0± 9.16
135 mg/m2/Week Dose (Phase I Only)39.1± 14.9
AUCweekly: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)20.8± 4.35
135 mg/m2/Week Dose (Phase I Only)25.7± 7.11
AUCweekly: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)32.4± 6.49
135 mg/m2/Week Dose (Phase I Only)39.0± 14.8
AUCinf: Day 1
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)28.7± 6.88
135 mg/m2/Week Dose (Phase I Only)37.1± 14.9
AUCinf: Day 15
GroupValue95% CI
100 mg/m2/Week Dose (Phase I Only)48.1± 19.6
135 mg/m2/Week Dose (Phase I Only)62.9± 34.1

Adverse events — posted to ClinicalTrials.gov

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). Phase 2 started before Phase 1 completed.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase I: 100 mg/m2/Week
Serious: 1/6 (17%)
Deaths: 5/6
Phase I: 135 mg/m2/Week
Serious: 2/6 (33%)
Deaths: 5/6
Phase II: 100 mg/m2/Week
Serious: 5/18 (28%)
Deaths: 9/18

Serious adverse events (8 terms)

ReactionSystemPhase I: 100 mg/m2/WeekPhase I: 135 mg/m2/WeekPhase II: 100 mg/m2/Week
Disease progressionGeneral disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Pathological fractureMusculoskeletal and connective tissue disorders
SepsisInfections and infestations
Device related bacteraemiaInfections and infestations
Device related infectionInfections and infestations
Peritonitis bacterialInfections and infestations
Other adverse events (79 terms — click to expand)

ReactionSystemPhase I: 100 mg/m2/WeekPhase I: 135 mg/m2/WeekPhase II: 100 mg/m2/Week
AstheniaGeneral disorders
Abdominal pain upperGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
HypertensionVascular disorders
Infusion site reactionGeneral disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ChromaturiaRenal and urinary disorders
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
HypotensionVascular disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Non-cardiac chest painGeneral disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
HaemoperitoneumGastrointestinal disorders
StomatitisGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Influenza like illnessGeneral disorders
Platelet count decreasedInvestigations
HeadacheNervous system disorders
AscitesGastrointestinal disorders
FatigueGeneral disorders
Infusion site painGeneral disorders
DysphagiaGastrointestinal disorders
EczemaSkin and subcutaneous tissue disorders
COVID-19Infections and infestations
LeukopeniaBlood and lymphatic system disorders
ThrombocytosisBlood and lymphatic system disorders
HyperthyroidismEndocrine disorders
HypothyroidismEndocrine disorders
MelaenaGastrointestinal disorders

Most-reported serious reactions: Disease progression, Anaemia, Neutropenia, Pathological fracture, Sepsis, Device related bacteraemia, Device related infection, Peritonitis bacterial.

Data from ClinicalTrials.gov NCT05630937 adverse events section.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Small-molecule-based targeted therapy in liver cancer.
    Ming Y, Gong Y, Fu X, Ouyang X, et al · · 2024 · cited 6× · PMID 39113358 · DOI 10.1016/j.ymthe.2024.08.001
  2. Systemic Therapy for Unresectable Hepatocellular Carcinoma: Current Landscape and Future Directions.
    Philippi Z, Reddy KD, Malik S, Al-Khalil Z, et al · · 2025 · cited 1× · PMID 40649773 · DOI 10.3390/ijms26135994

Verify or expand the search:

Other recruiting trials for Unresectable Hepatocellular Carcinoma (HCC)

Currently open trials in the same condition.

Other Nerviano Medical Sciences trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT05630937.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing