Efficacy and Safety of Momelotinib Combined With Trametinib in Adults With Metastatic KRAS-mutated Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Platinum-Based Chemotherapy Preceded by a Dose-finding Lead-in Phase

NCT02258607 | Terminated Phase 1 FDA Drug

• 1 other identifier: GS-US-370-1297
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

Brief Summary

This study is conducted in two phases. The Dose-finding Lead-in Phase, Part A, will evaluate the safety and determine the maximum tolerated dose (MTD) of momelotinib (MMB) when combined with trametinib. Once the MTD of momelotinib (MMB) is determined, the study will proceed to the Dose-finding Lead-in Phase, Part B, to determine the MTD of trametinib. After the MTD is established, the study may proceed to an expansion phase to determine the efficacy, safety, and tolerability of MMB combined with trametinib at the MTD in participants with kirsten rat sarcoma viral oncogene homolog (KRAS) mutated metastatic non-small cell lung cancer (NSCLC). Each treatment cycle will consist of 28 days and treatment will continue in the absence of disease progression, unacceptable toxicity, consent withdrawal, or participant's refusal of treatment.

Conditions

Relapsed Metastatic KRAS-Mutated Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• For the Dose-finding Lead-in Phase, incidence of dose limiting toxicities (DLTs)

  Dose limiting toxicities (DLTs) refer to toxicities experienced during the first 28 days of treatment that have been judged to be clinically significant and at least possibly related to study treatment.

  Up to 28 days

• For Expansion Phase, disease control rate (DCR) at Week 8

  Disease control rate (DCR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumor (RECIST) v1.1.

  Week 8

Secondary Outcomes (8)

• For the Dose-finding Lead-in Phase, disease control rate (DCR) at Week 8

  Week 8

• For the Dose-finding Lead-in Phase, overall survival

  Up to 2 years

• For the Dose-finding Lead-in Phase, progression free survival (PFS)

  Up to 2 years

• For the Dose-finding Lead-in Phase, overall response rate (ORR)

  Up to 2 years

• For the Dose-finding Lead-in Phase, plasma pharmacokinetics (PK) parameters of momelotinib (MMB) and major metabolite GS-644603 as measured by Cmax and AUCtau

  Days 1 and 15 (Cycle 1 only)

Study Arms (3)

Momelotinib (MMB) dose escalation

EXPERIMENTAL

Participants will receive momelotinib (MMB) plus trametinib. Momelotinib (MMB) dose will increase to find the MTD.

Drug: Momelotinib (MMB); Drug: Trametinib

Trametinib dose escalation

EXPERIMENTAL

Participants will receive momelotinib (MMB) plus trametinib. Trametinib dose will increase to find the MTD.

Drug: Momelotinib (MMB); Drug: Trametinib

Momelotinib (MMB)+trametinib

EXPERIMENTAL

Expansion Phase: participants will receive momelotinib (MMB) plus trametinib for the duration of the study.

Drug: Momelotinib (MMB); Drug: Trametinib

Interventions

Momelotinib (MMB) DRUG

Momelotinib (MMB) tablet(s) administered orally once or twice daily

Also known as: GS-0387, CYT387

Momelotinib (MMB) dose escalation; Momelotinib (MMB)+trametinib; Trametinib dose escalation

Trametinib DRUG

Trametinib tablet administered orally once daily

Momelotinib (MMB) dose escalation; Momelotinib (MMB)+trametinib; Trametinib dose escalation

Eligibility Criteria

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

You may qualify if:

• Individuals with KRAS-mutated metastatic or recurrent non-small cell lung cancer
• Radiologic documentation of disease progression
• Measurable disease per RECIST v1.1
• Adequate organ function defined as follows:
• Hepatic: Total conjugated bilirubin ≤ 1.25 x upper limit of normal (ULN); aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x upper limit of normal (ULN) or \< 5 x ULN in the setting of liver metastases
• Hematological: Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelet ≥ 100 x 10\^9/L, hemoglobin ≥ 9 g/dL
• Renal: Serum creatinine \< 1.5 x ULN OR calculated creatinine clearance (CLcr) ≥ 60 ml/min
• Adequate left ventricular ejection fraction (LVEF) ≥ 50%
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Negative serum pregnancy test for females

You may not qualify if:

• Less than or equal to 3 weeks since receiving treatment with biologic, small molecule, chemotherapy or other agent for non-small cell lung cancer and 28 days since any prior immunotherapy (such as nivolumab)
• History of a concurrent or second malignancy, except for specified exceptions in the protocol or any other cancer that has been in complete remission for ≥ 5 years
• Known positive status for human immunodeficiency virus (HIV)
• Chronic active or acute viral hepatitis A, B, or C infection or hepatitis B or C carrier
• Presence of ≥ Grade 2 peripheral neuropathy
• Brain metastases, or spinal cord compression. Individuals with brain metastases are allowed if they have been treated with irradiation or surgery, are clinically stable without steroid treatment. Individuals with documented leptomeningeal disease are not eligible
• A history of uveitis and/or scleritis
• Retinal pathology beyond normal age-related processes
• Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal vein occlusion
• History of newly diagnosed or uncontrolled glaucoma/intraocular pressure \> 21 mm Hg as measured by tonography
• Use of daily and/or chronic oral or ocular steroids. Individuals must be off daily steroids for at least 3 weeks prior to enrolling into the trial
• History of interstitial pneumonitis
• History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (\> 480 ms for males and females)

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (5)

Unknown Facility

Duarte, California, United States

Location

Unknown Facility

Sacramento, California, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Fairfax, Virginia, United States

Location

Unknown Facility

Spokane, Washington, United States

Location

Related Publications (1)

• Barbie DA, Spira A, Kelly K, Humeniuk R, Kawashima J, Kong S, Koczywas M. Phase 1B Study of Momelotinib Combined With Trametinib in Metastatic, Kirsten Rat Sarcoma Viral Oncogene Homolog-Mutated Non-Small-Cell Lung Cancer After Platinum-Based Chemotherapy Treatment Failure. Clin Lung Cancer. 2018 Nov;19(6):e853-e859. doi: 10.1016/j.cllc.2018.07.004. Epub 2018 Aug 4.

  PMID: 30087028 DERIVED

MeSH Terms

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; trametinib

Study Officials

• Gilead Study Director

  Gilead Sciences

  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: October 3, 2014
• First Posted: October 7, 2014
• Study Start: March 11, 2015
• Primary Completion: July 19, 2016
• Study Completion: February 27, 2017
• Last Updated: February 1, 2019

Record last verified: 2019-01

Locations

US (5)