TerminatedNCT02601378Updated Sep 29, 2022

A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.

A Phase 1 interventional study of LXS196 and LXS196 and HDM201 in Uveal Melanoma, sponsored by Novartis Pharmaceuticals. Terminated at 6 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-09-29.

Sponsored by Novartis Pharmaceuticals · Phase 1, Interventional, and Treatment

Why this study was terminated

The combination part of the study was terminated early due to business reasons

From the registry’s dates

Primary completion was Jan 2022, 4 years 9 months ago, and no results have been posted to the registry.

Phase: Phase 1
Study type: Interventional
Enrollment: 107
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma.

Conditions studied

Uveal Melanoma

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Keywords

Uveal melanoma
Metastatic uveal melanoma
Phase I
LXS196
PKC inhibitor
HDM201
HDM2 inhibitor
dose escalation

In context

Melanoma

3,005 studies on the registry are indexed under Melanoma; 519 are open to participants now.

This study's enrollment of 107 is above the median of 38 across 2,350 interventional studies indexed under Melanoma.

Browse Melanoma studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Key Inclusion Criteria:

Male or female patients ≥18 years of age
Diagnosis of uveal melanoma with histological or cytological confirmed metastatic disease. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent therapy.
Willingness to provide newly obtained tumor tissue at baseline and on treatment unless contraindicated by medical risk in the opinion of the treating physician.
Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as >10 mm with CT scan.
ECOG performance status ≤ 1

Key Exclusion Criteria:

Malignant disease other than that being treated in this study.
Symptomatic or untreated CNS metastases or spinal cord compression. Brain metastasis must be stable with verification by imaging .
Impaired cardiac function or clinically significant cardiac diseases
History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism (applicable to combination part only).
Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following:
known and possible risk for QT prolongation
known to be strong inducers or inhibitors of CYP3A4/5 (for single agent part); known to be moderate to strong inducers or inhibitors of CYP3A4/5 (for combination part)
known to be inducers or inhibitors of P-gp
known to be substrates of CYP3A4/5 and P-gp with a narrow therapeutic index
Patients with abnormal laboratory values, defined as any of the following:
AST or ALT > 3 times ULN, AST or ALT > 5 times ULN for patients with liver metastases.
Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN.
Absolute neutrophil count (ANC) ≤ 1.5 x109/L.
Platelets ≤ 100 x 109/L.
Hemoglobin (Hgb) ≤ 90 g/L (9 g/dL).
Creatinine > 1.5 x ULN
Patients receiving live vaccines due to the expected bone marrow toxicity (applicable to combination part only).
Patients treated with growth factors targeting the myeloid lineage (e.g. G-CSF, GM-CSF and M-CSF) within 2 weeks of starting study treatment. (applicable to combination part only).

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 107 participants (actual)

Study arms

Experimental
LXS196 as a single agent
About 68 patients will be enrolled in dose escalation and expansion
Drug: LXS196
Experimental
LXS196 in combination with HDM201
about 44 patients to be enrolled in dose escalation and expansion
Drug: LXS196 and HDM201

Interventions

DrugLXS196
LXS196 as a single agent
DrugLXS196 and HDM201
LXS196 in combination with HDM201

What researchers measure

Primary outcomes

Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
cycle = 28 days
Time frame: Cycle 1 in dose escalation
Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients)
Time frame: Continuously throughout the study until 30 days after treatment discontinuation
Dose interruptions, reductions and dose intensity
Time frame: Continuously throughout the study until 30 days after treatment discontinuation

Secondary outcomes

Overall response rate (ORR) per RECIST version 1.1 criteria
Time frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma LXS196 concentration-time profiles as a single agent
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Modulation of signaling molecules downstream of PKC
Time frame: Baseline and Cycle 1 Day 15
Progression free survival (PFS) per RECIST version 1.1 criteria
Time frame: From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months
Plasma PK parameters of LXS196 as a single agent:AUC
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 as a single agent: Racc
Time frame: Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1
Plasma HDM201 concentration-time profiles
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: AUC
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma PK parameters of HDM201: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1
Plasma LXS196 concentration-time profiles in combination with HDM201
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201:AUC
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Cmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Tmax
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: t1/2
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
Plasma PK parameters of LXS196 in combination with HDM201: Racc
Time frame: Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1
LXS196 plasma protein binding as a single agent
Time frame: Cycle 1 Day 1, 2, 15, 16
LXS196 plasma protein content as a single agent
Time frame: Cycle 1, 2, 3 and 4 Day 1

Study locations

6 sites

Columbia University Medical Center
New York, New York 10032, United States
Novartis Investigative Site
Westmead, New South Wales 2145, Australia
Novartis Investigative Site
Paris, 75231, France
Novartis Investigative Site
Leiden, 2300 RC, Netherlands
Novartis Investigative Site
Oslo, 0379, Norway
Novartis Investigative Site
Madrid, 28050, Spain

References and documents

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 29, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02601378
Lead sponsor: Novartis Pharmaceuticals
Responsible party: Sponsor
First posted: Nov 10, 2015
Start date: Feb 1, 2016
Primary completion: Jan 7, 2022
Completion: Jan 7, 2022
Last update: Sep 29, 2022

Study contacts

Novartis Pharmaceuticals

study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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