A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02974725 |
Recruitment Status :
Active, not recruiting
First Posted : November 28, 2016
Last Update Posted : April 16, 2024
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Non-Small Cell Lung Cancer Melanoma | Drug: LXH254 Drug: LTT462 Drug: Trametinib Drug: Ribociclib | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 242 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | February 24, 2017 |
Estimated Primary Completion Date : | May 1, 2024 |
Estimated Study Completion Date : | May 1, 2024 |
Arm | Intervention/treatment |
---|---|
Experimental: LXH254+LTT462 |
Drug: LXH254
LXH254 will be supplied as tablet for oral use. Drug: LTT462 LTT462 will be supplied as hard gelatin capsule for oral use. |
Experimental: LXH254+Trametinib |
Drug: LXH254
LXH254 will be supplied as tablet for oral use. Drug: Trametinib Trametinib will be supplied as film-coated tablet for oral use |
Experimental: LXH254+Ribociclib |
Drug: LXH254
LXH254 will be supplied as tablet for oral use. Drug: Ribociclib Ribociclib will be supplied in tablets and hard gelatin capsules. |
- Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [ Time Frame: up to 5 years ]
- Dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: up to 3 years ]
- 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 ]
- 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 ]
- Overall Response Rate (ORR) [ Time Frame: Up to 5 years ]
- Duration of response (DOR) [ Time Frame: Up to 5 years ]
- Disease Control Rate (DCR) [ Time Frame: Up to 5 years ]
- Progression Free Survival (PFS) [ Time Frame: Up to 5 years ]
- Overall Survival (OS) - (dose expansion part only) [ Time Frame: Up to 5 years ]
- Derived PK parameter (Cmax) for LXH254 & LTT462: [ Time Frame: Up to 5 years ]
- Derived PK parameter (AUC) for LXH254 & LTT462 [ Time Frame: Up to 5 years ]
- Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples [ Time Frame: up to 5 years ]
- Derived PK parameter (Cmax) for LXH254 & trametinib [ Time Frame: up to 5 years ]
- Derived PK parameter (AUC) for LXH254 & trametinib [ Time Frame: Up to 5 years ]
- Derived PK parameter (Cmax) for LXH254 & ribociclib [ Time Frame: Up to 5 years ]
- Derived PK parameter (AUC) for LXH254 & ribociclib [ Time Frame: Up to 5 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974725
United States, California | |
University of California San Diego . | |
San Diego, California, United States, 92103 | |
UCSF Medical Center | |
San Francisco, California, United States, 94143 | |
United States, Massachusetts | |
Massachusetts General Hospital SC | |
Boston, Massachusetts, United States, 02114 | |
United States, New York | |
Memorial Sloan Kettering Cancer Ctr . | |
New York, New York, United States, 10065 | |
United States, Tennessee | |
Sarah Cannon Research Institute Tennessee Oncology | |
Nashville, Tennessee, United States, 37203 | |
United States, Texas | |
Uni of TX MD Anderson Cancer Cntr | |
Houston, Texas, United States, 77030 | |
Australia, New South Wales | |
Novartis Investigative Site | |
Westmead, New South Wales, Australia, 2145 | |
Australia, Victoria | |
Novartis Investigative Site | |
Melbourne, Victoria, Australia, 3000 | |
Belgium | |
Novartis Investigative Site | |
Leuven, Belgium, 3000 | |
France | |
Novartis Investigative Site | |
Lyon, France, 69373 | |
Novartis Investigative Site | |
Paris 10, France, 75475 | |
Novartis Investigative Site | |
Villejuif, France, 94800 | |
Germany | |
Novartis Investigative Site | |
Dresden, Germany, 01307 | |
Novartis Investigative Site | |
Essen, Germany, 45147 | |
Novartis Investigative Site | |
Frankfurt, Germany, 60590 | |
Novartis Investigative Site | |
Koeln, Germany, 50937 | |
Israel | |
Novartis Investigative Site | |
Tel Aviv, Israel, 6423906 | |
Italy | |
Novartis Investigative Site | |
Milano, MI, Italy, 20133 | |
Novartis Investigative Site | |
Milano, MI, Italy, 20162 | |
Novartis Investigative Site | |
Rozzano, MI, Italy, 20089 | |
Novartis Investigative Site | |
Verona, VR, Italy, 37126 | |
Novartis Investigative Site | |
Napoli, Italy, 80131 | |
Korea, Republic of | |
Novartis Investigative Site | |
Seoul, Korea, Republic of, 03080 | |
Novartis Investigative Site | |
Seoul, Korea, Republic of, 06351 | |
Poland | |
Novartis Investigative Site | |
Warszawa, Poland, 02 781 | |
Spain | |
Novartis Investigative Site | |
Sevilla, Andalucia, Spain, 41013 | |
Novartis Investigative Site | |
Barcelona, Catalunya, Spain, 08035 | |
Novartis Investigative Site | |
Barcelona, Catalunya, Spain, 08036 | |
Novartis Investigative Site | |
Valencia, Comunidad Valenciana, Spain, 46010 | |
Novartis Investigative Site | |
Pamplona, Navarra, Spain, 31008 | |
Novartis Investigative Site | |
Madrid, Spain, 28034 | |
Sweden | |
Novartis Investigative Site | |
Stockholm, Sweden, 171 76 |
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT02974725 |
Other Study ID Numbers: |
CLXH254X2102 2016-004293-18 ( EudraCT Number ) |
First Posted: | November 28, 2016 Key Record Dates |
Last Update Posted: | April 16, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Lung Neoplasms Carcinoma, Non-Small-Cell Lung Melanoma Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Neuroendocrine Tumors Neuroectodermal Tumors |
Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Nerve Tissue Nevi and Melanomas Skin Neoplasms Skin Diseases Trametinib Naporafenib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |