Clinical Trial - NCT02974725

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

Recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02974725

Protocol Info

Short Description: Phase 1 b LXH254 + TT462 in KRAS or BRAF mutant NSCLC
Long Description: A Phase lb, open-label, multicenter study of oral LXH254 in combination with oral L TT462 in adult patients with advanced or metastatic KRAS or BRAF mutant Non-Small Cell Lung Cancer
MGH Status: Open
Sponsor: Novartis
Disease Program: Thoracic

Next Steps


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Purpose

To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
Condition Title Intervention Phase
Non-Small Cell Lung Cancer Melanoma LXH254 LTT462 Trametinib LXH254 Ribociclib Phase 1
Study Type Interventional
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

Primary Outcome Measures

Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [Time Frame: 12 months] [Designated as safety issue: ]

Dose limiting toxicities (DLTs) (dose escalation only) [Time Frame: 1 cycle (28 days)] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Response Rate (ORR) [Time Frame: Up to 12 months] [Designated as safety issue: ]

Duration of response (DOR) [Time Frame: Up to 12 months] [Designated as safety issue: ]

Disease Control Rate (DCR) [Time Frame: Up to 12 months] [Designated as safety issue: ]

Progression Free Survival (PFS) [Time Frame: Up to 12 months] [Designated as safety issue: ]

Overall Survival (OS) - (dose expansion part only) [Time Frame: Up to 12 months] [Designated as safety issue: ]

Plasma concentrations of LXH254 [Time Frame: Up to Month 5] [Designated as safety issue: ]

Plasma concentrations of LTT462 [Time Frame: Up to Month 5] [Designated as safety issue: ]

Derived PK parameter (Cmax) for LXH254 & LTT462: [Time Frame: Up to Month 5] [Designated as safety issue: ]

Derived PK parameter (AUC) for LXH254 & LTT462 [Time Frame: Up to Month 5] [Designated as safety issue: ]

Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples [Time Frame: baseline, month 12] [Designated as safety issue: ]

Plasma concentrations of trametinib [Time Frame: Up to Month 5] [Designated as safety issue: ]

Derived PK parameter (Cmax) for LXH254 & trametinib [Time Frame: Up to Month 5] [Designated as safety issue: ]

Derived PK parameter (AUC) for LXH254 & trametinib [Time Frame: Up to Month 5] [Designated as safety issue: ]

Plasma concentrations of ribociclib [Time Frame: Up to Month 5] [Designated as safety issue: ]

Derived PK parameter (Cmax) for LXH254 & ribociclib [Time Frame: Up to Month 5] [Designated as safety issue: ]

Derived PK parameter (AUC) for LXH254 & ribociclib [Time Frame: Up to Month 5] [Designated as safety issue: ]

Estimated Enrollment: 127
Study Start Date: February 2017
Estimated Study Completion Date: June 2020
Estimated Primary Completion Date: June 2019
Arms Assigned Interventions

Experimental:LXH254+LTT462

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

Experimental:LXH254+Trametinib

Drug:LXH254
Trametinib will be supplied as film-coated tablet for oral use

Experimental:LXH254+Ribociclib

Drug:Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Patients must have advanced or metastatic NSCLC or melanoma
  • Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (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. BRAF mutant patients group: Prior treatment with an ERKi and/or a pan-RAFi.
  • 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02974725

Locations

  • United States, Massachusetts
    • Novartis Investigative Site Boston, Massachusetts, United States, 02114
  • Australia, Victoria
    • Novartis Investigative Site Melbourne, Victoria, Australia, 3000
  • Belgium,
    • Novartis Investigative Site Leuven, , Belgium, 3000
  • France,
    • Novartis Investigative Site Villejuif Cedex, , France, 94805
  • Germany,
    • Novartis Investigative Site Frankfurt, , Germany, 60590
    • Novartis Investigative Site Koeln, , Germany, 50937
  • Italy, MI
    • Novartis Investigative Site Rozzano, MI, Italy, 20089
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08036

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02974725
Other Study ID Numbers: 2016-004293-18
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

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

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Melanoma

Trametinib

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019