Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations

NCT02607813 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CLXH254X21012015-003421-33
• Study Type: interventional
• Target: 142
• Locations: 10 countries
• Sites: 18

Brief Summary

A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.

Conditions

NSCLC; Ovarian Cancer; Melanoma; Other Solid Tumors

Keywords

LXH254, CRAF, MAPK, solid tumor, PDR001

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity.

  cycle = 28 days

  From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)

• Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only)

  cycle = 28 days

  28 days

• Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only)

  cycle =28 days

  56 days

Secondary Outcomes (16)

• Overall response rate (ORR)

  Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months

• Disease control rate (DCR)

  Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months

• Duration of response (DoR)

  Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months

• Progression-free survival (PFS)

  Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months

• Overall survival (OS) - only for dose expansion

  From time of start treatment until the date of death; expected duration approximately 12 months

Study Arms (6)

Dose escalation LXH254

EXPERIMENTAL

Drug: LXH254

Dose expansion LXH254: Group 1

EXPERIMENTAL

Drug: LXH254

Dose expansion LXH254: Group 2

EXPERIMENTAL

Drug: LXH254

Dose expansion LXH254: Group 3

EXPERIMENTAL

Drug: LXH254

Dose expansion: LXH254 + PDR001

EXPERIMENTAL

Drug: LXH254; Drug: PDR001

Dose escalation LXH254 + PDR001

EXPERIMENTAL

Drug: LXH254; Drug: PDR001

Interventions

LXH254 DRUG

pan-RAF inhibitor

Dose escalation LXH254; Dose escalation LXH254 + PDR001; Dose expansion LXH254: Group 1; Dose expansion LXH254: Group 2; Dose expansion LXH254: Group 3; Dose expansion: LXH254 + PDR001

PDR001 DRUG

Biological: PDR001 anti-PD1 antibody

Dose escalation LXH254 + PDR001; Dose expansion: LXH254 + PDR001

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Presence of at least one measurable lesion according to RECIST v1.1.
• Documented MAPK alteration
• Patients with confirmed KRAS-mutated NSCLC
• Patients with confirmed NRAS-mutated melanoma (cutaneous melanoma only)

You may not qualify if:

• \- Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled in the dose expansion part.
• Exceptions may be made after documented agreement between Novartis and Investigator.
• 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 which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
• Pregnant or nursing (lactating) women
• History of severe hypersensitivity reactions, which in the opinion of the investigator may cause in increased risk of serious infusion reaction.
• Known human immunodeficiency virus (HIV).
• Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
• Active, known or suspected autoimmune disease.
• Active infection requiring systemic antibiotic therapy
• Patients requiring systemic steroid therapy or any immunosuppressive therapy (≥10mg/day prednisone or equivalent) which cannot be discontinued at least 7 days prior to first dose of study treatment.
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

Massachusetts General Hospital MGH Cancer Center

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center SC - LXH254X2101

New York, New York, 10065, United States

Location

UT M.D Anderson Cancer Center SC - LXH254X2101

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2C1, Canada

Location

Novartis Investigative Site

Paris, 75475, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Modena, MO, 41124, Italy

Location

Novartis Investigative Site

Napoli, 80131, Italy

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

Location

Medical Oncology, Erasmus MC

Rotterdam, 3075 CE, Netherlands

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Related Links

• Study Results

MeSH Terms

Conditions

Ovarian Neoplasms; Melanoma

Interventions

naporafenib; spartalizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2015
• First Posted: November 18, 2015
• Study Start: January 18, 2016
• Primary Completion: February 18, 2022
• Study Completion: February 19, 2022
• Last Updated: December 21, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); CA (1); FR (2); JP (1); CH (1); US (3); DE (1); ES (3); KR (1); NL (2)