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

NCT ID: NCT02974725

Last Updated: 2025-04-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

241 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-24

Study Completion Date

2024-04-24

Brief Summary

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

Detailed Description

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Conditions

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Non-Small Cell Lung Cancer Melanoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LXH254+LTT462

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

LXH254 will be supplied as tablet for oral use.

LTT462

Intervention Type DRUG

LTT462 will be supplied as hard gelatin capsule for oral use.

LXH254+Trametinib

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

LXH254 will be supplied as tablet for oral use.

Trametinib

Intervention Type DRUG

Trametinib will be supplied as film-coated tablet for oral use

LXH254+Ribociclib

Group Type EXPERIMENTAL

LXH254

Intervention Type DRUG

LXH254 will be supplied as tablet for oral use.

Ribociclib

Intervention Type DRUG

Ribociclib will be supplied in tablets and hard gelatin capsules.

Interventions

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LXH254

LXH254 will be supplied as tablet for oral use.

Intervention Type DRUG

LTT462

LTT462 will be supplied as hard gelatin capsule for oral use.

Intervention Type DRUG

Trametinib

Trametinib will be supplied as film-coated tablet for oral use

Intervention Type DRUG

Ribociclib

Ribociclib will be supplied in tablets and hard gelatin capsules.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of California San Diego .

San Diego, California, United States

Site Status

UCSF Medical Center

San Francisco, California, United States

Site Status

Massachusetts General Hospital SC

Boston, Massachusetts, United States

Site Status

Memorial Sloan Kettering Cancer Ctr .

New York, New York, United States

Site Status

Sarah Cannon Research Institute Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Uni of TX MD Anderson Cancer Cntr

Houston, Texas, United States

Site Status

Novartis Investigative Site

Westmead, New South Wales, Australia

Site Status

Novartis Investigative Site

Melbourne, Victoria, Australia

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Lyon, , France

Site Status

Novartis Investigative Site

Paris, , France

Site Status

Novartis Investigative Site

Villejuif, , France

Site Status

Novartis Investigative Site

Cologne, , Germany

Site Status

Novartis Investigative Site

Dresden, , Germany

Site Status

Novartis Investigative Site

Essen, , Germany

Site Status

Novartis Investigative Site

Frankfurt, , Germany

Site Status

Novartis Investigative Site

Tel Aviv, , Israel

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Rozzano, MI, Italy

Site Status

Novartis Investigative Site

Verona, VR, Italy

Site Status

Novartis Investigative Site

Napoli, , Italy

Site Status

Novartis Investigative Site

Warsaw, , Poland

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seoul, , South Korea

Site Status

Novartis Investigative Site

Seville, Andalusia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Novartis Investigative Site

Pamplona, Navarre, Spain

Site Status

Novartis Investigative Site

Valencia, Valencia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Stockholm, , Sweden

Site Status

Countries

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United States Australia Belgium France Germany Israel Italy Poland South Korea Spain Sweden

References

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Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist RS, Sun JM, Min Kim T, Reguart N, Sanmamed MF, Felip E, Garrido P, Santoro A, Bootle D, Couillebault XM, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer. 2024 Nov;197:107964. doi: 10.1016/j.lungcan.2024.107964. Epub 2024 Sep 26.

Reference Type DERIVED
PMID: 39383771 (View on PubMed)

de Braud F, Dooms C, Heist RS, Lebbe C, Wermke M, Gazzah A, Schadendorf D, Rutkowski P, Wolf J, Ascierto PA, Gil-Bazo I, Kato S, Wolodarski M, McKean M, Munoz Couselo E, Sebastian M, Santoro A, Cooke V, Manganelli L, Wan K, Gaur A, Kim J, Caponigro G, Couillebault XM, Evans H, Campbell CD, Basu S, Moschetta M, Daud A. Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study. J Clin Oncol. 2023 May 10;41(14):2651-2660. doi: 10.1200/JCO.22.02018. Epub 2023 Mar 22.

Reference Type DERIVED
PMID: 36947734 (View on PubMed)

Related Links

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Other Identifiers

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2016-004293-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLXH254X2102

Identifier Type: -

Identifier Source: org_study_id

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