Clinical trial NCT02974725: A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma
Official title: A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Melanoma
Keywords: NSCLC
Melanoma
NRAS
KRAS
BRAF
LXH254
LTT462
Trametinib
Ribocliclib
Non-small cell lung carcinoma (NSCLC)
treatment of lung cancer after first metastasis
lung cancer
lung adenocarcinoma
Large-cell lung carcinoma
Non small cell lung carcinoma
Non small cell lung cancer
Large cell lung carcinoma
Large cell lung cancer
squamous cell lung carcinoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-11-28
Enrollment: 241
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.


Eligibility criteria: Inclusion Criteria:

* Patients must have advanced or metastatic NSCLC or cutaneous melanoma
* Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
* All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
* ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2

Exclusion Criteria:

-Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed).

Patients who have received more than 3 lines of anti-cancer therapy are excluded.

* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
* Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
* Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
* Patients with Gilbert's syndrome or other heritable diseases of bile processing.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
timeFrame: up to 5 years
measure: Dose limiting toxicities (DLTs) (dose escalation only)
timeFrame: up to 3 years
measure: Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
timeFrame: up to 5 years
measure: Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 5 years
measure: Duration of response (DOR)
timeFrame: Up to 5 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 5 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 5 years
measure: Overall Survival (OS) - (dose expansion part only)
timeFrame: Up to 5 years
measure: Derived PK parameter (Cmax) for LXH254 & LTT462:
timeFrame: Up to 5 years
measure: Derived PK parameter (AUC) for LXH254 & LTT462
timeFrame: Up to 5 years
measure: Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
timeFrame: up to 5 years
measure: Derived PK parameter (Cmax) for LXH254 & trametinib
timeFrame: up to 5 years
measure: Derived PK parameter (AUC) for LXH254 & trametinib
timeFrame: Up to 5 years
measure: Derived PK parameter (Cmax) for LXH254 & ribociclib
timeFrame: Up to 5 years
measure: Derived PK parameter (AUC) for LXH254 & ribociclib
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego .
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital SC
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Ctr .
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: Uni of TX MD Anderson Cancer Cntr
state: Texas
city: Westmead
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Paris 10
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Verona
country: Italy
facility: Novartis Investigative Site
state: VR
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: