A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02974725
• Other study ID #: CLXH254X2102
• Secondary ID: 2016-004293-18
• Status: Terminated
• Phase: Phase 1
• Start date: February 24, 2017
• Est. completion date: April 24, 2024

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 241
• Est. completion date: April 24, 2024
• Est. primary completion date: April 24, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Melanoma
• Non-Small Cell Lung Cancer

Intervention

Drug:
• LXH254
LXH254 will be supplied as tablet for oral use.
• LTT462
LTT462 will be supplied as hard gelatin capsule for oral use.
• Trametinib
Trametinib will be supplied as film-coated tablet for oral use
• Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Melbourne	Victoria
Australia	Novartis Investigative Site	Westmead	New South Wales
Belgium	Novartis Investigative Site	Leuven
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Paris 10
France	Novartis Investigative Site	Villejuif
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Koeln
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Rozzano	MI
Italy	Novartis Investigative Site	Verona	VR
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Poland	Novartis Investigative Site	Warszawa
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Pamplona	Navarra
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Sweden	Novartis Investigative Site	Stockholm
United States	Massachusetts General Hospital SC	Boston	Massachusetts
United States	Uni of TX MD Anderson Cancer Cntr	Houston	Texas
United States	Sarah Cannon Research Institute Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Ctr .	New York	New York
United States	University of California San Diego .	San Diego	California
United States	UCSF Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Germany,  Israel,  Italy,  Korea, Republic of,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs) as a measure of safety and tolerability		up to 5 years
Primary	Dose limiting toxicities (DLTs) (dose escalation only)		up to 3 years
Primary	Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions		up to 5 years
Primary	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		Up to 5 years
Secondary	Overall Response Rate (ORR)		Up to 5 years
Secondary	Duration of response (DOR)		Up to 5 years
Secondary	Disease Control Rate (DCR)		Up to 5 years
Secondary	Progression Free Survival (PFS)		Up to 5 years
Secondary	Overall Survival (OS) - (dose expansion part only)		Up to 5 years
Secondary	Derived PK parameter (Cmax) for LXH254 & LTT462:		Up to 5 years
Secondary	Derived PK parameter (AUC) for LXH254 & LTT462		Up to 5 years
Secondary	Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples		up to 5 years
Secondary	Derived PK parameter (Cmax) for LXH254 & trametinib		up to 5 years
Secondary	Derived PK parameter (AUC) for LXH254 & trametinib		Up to 5 years
Secondary	Derived PK parameter (Cmax) for LXH254 & ribociclib		Up to 5 years
Secondary	Derived PK parameter (AUC) for LXH254 & ribociclib		Up to 5 years