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

Primary Purpose

Non-Small Cell Lung Cancer, Melanoma

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LXH254
LTT462
Trametinib
Ribociclib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of California San Diego .
  • UCSF Medical Center
  • Massachusetts General Hospital SC
  • Memorial Sloan Kettering Cancer Ctr .
  • Sarah Cannon Research Institute Tennessee Oncology
  • Uni of TX MD Anderson Cancer Cntr
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

LXH254+LTT462

LXH254+Trametinib

LXH254+Ribociclib

Arm Description

Outcomes

Primary Outcome Measures

Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
Dose limiting toxicities (DLTs) (dose escalation only)
Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
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

Secondary Outcome Measures

Overall Response Rate (ORR)
Duration of response (DOR)
Disease Control Rate (DCR)
Progression Free Survival (PFS)
Overall Survival (OS) - (dose expansion part only)
Derived PK parameter (Cmax) for LXH254 & LTT462:
Derived PK parameter (AUC) for LXH254 & LTT462
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
Derived PK parameter (Cmax) for LXH254 & trametinib
Derived PK parameter (AUC) for LXH254 & trametinib
Derived PK parameter (Cmax) for LXH254 & ribociclib
Derived PK parameter (AUC) for LXH254 & ribociclib

Full Information

First Posted
November 23, 2016
Last Updated
October 3, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02974725
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 24, 2017 (Actual)
Primary Completion Date
April 26, 2024 (Anticipated)
Study Completion Date
April 26, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
242 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LXH254+LTT462
Arm Type
Experimental
Arm Title
LXH254+Trametinib
Arm Type
Experimental
Arm Title
LXH254+Ribociclib
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LXH254
Intervention Description
LXH254 will be supplied as tablet for oral use.
Intervention Type
Drug
Intervention Name(s)
LTT462
Intervention Description
LTT462 will be supplied as hard gelatin capsule for oral use.
Intervention Type
Drug
Intervention Name(s)
Trametinib
Intervention Description
Trametinib will be supplied as film-coated tablet for oral use
Intervention Type
Drug
Intervention Name(s)
Ribociclib
Intervention Description
Ribociclib will be supplied in tablets and hard gelatin capsules.
Primary Outcome Measure Information:
Title
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
Time Frame
up to 5 years
Title
Dose limiting toxicities (DLTs) (dose escalation only)
Time Frame
up to 3 years
Title
Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
Time Frame
up to 5 years
Title
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
Time Frame
Up to 5 years
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Time Frame
Up to 5 years
Title
Duration of response (DOR)
Time Frame
Up to 5 years
Title
Disease Control Rate (DCR)
Time Frame
Up to 5 years
Title
Progression Free Survival (PFS)
Time Frame
Up to 5 years
Title
Overall Survival (OS) - (dose expansion part only)
Time Frame
Up to 5 years
Title
Derived PK parameter (Cmax) for LXH254 & LTT462:
Time Frame
Up to 5 years
Title
Derived PK parameter (AUC) for LXH254 & LTT462
Time Frame
Up to 5 years
Title
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
Time Frame
up to 5 years
Title
Derived PK parameter (Cmax) for LXH254 & trametinib
Time Frame
up to 5 years
Title
Derived PK parameter (AUC) for LXH254 & trametinib
Time Frame
Up to 5 years
Title
Derived PK parameter (Cmax) for LXH254 & ribociclib
Time Frame
Up to 5 years
Title
Derived PK parameter (AUC) for LXH254 & ribociclib
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of California San Diego .
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
UCSF Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Massachusetts General Hospital SC
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Ctr .
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Sarah Cannon Research Institute Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Uni of TX MD Anderson Cancer Cntr
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Novartis Investigative Site
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Novartis Investigative Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Novartis Investigative Site
City
Paris 10
ZIP/Postal Code
75475
Country
France
Facility Name
Novartis Investigative Site
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20162
Country
Italy
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Verona
State/Province
VR
ZIP/Postal Code
37126
Country
Italy
Facility Name
Novartis Investigative Site
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
02 781
Country
Poland
Facility Name
Novartis Investigative Site
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41013
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08036
Country
Spain
Facility Name
Novartis Investigative Site
City
Valencia
State/Province
Comunidad Valenciana
ZIP/Postal Code
46010
Country
Spain
Facility Name
Novartis Investigative Site
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Novartis Investigative Site
City
Stockholm
ZIP/Postal Code
171 76
Country
Sweden

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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