RO5126766 for Patients With Advanced KRAS-Mutant Lung Cancer

NCT03681483 | Completed Phase 1 FDA Drug

• 1 other identifier: 18-285
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the safety of RO5126766 at different doses to find out what effects, if any, it has on people with advanced lung cancer who have previously received treatment with a PD-1 or PD-L1 inhibitor.

Conditions

Advanced Non-small Cell Lung Cancer

Keywords

RO5126766 (CH5126766); KRAS-Mutant; 18-285

Outcome Measures

Primary Outcomes (2)

• The maximum tolerated dose (MTD)

  will be defined as the highest dose level at which ≤ 1 of 6 patients experienced a DLT.The NCI Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE) will be used to grade toxicities during the trial. DLTs are defined as any toxicity occurring during the first cycle of treatment (i.e. 4 weeks), excluding toxicites clearly related to disease progression or disease-related processes.

  1 year

• overall response rate (dose expansion)

  by RECIST 1.1

  1 year

Study Arms (1)

RO5126766 (CH5126766)

EXPERIMENTAL

The study will begin with a standard 3+3 design. The study will enroll 3 patients at the previously identified MTD15 (4mg two times per week on days 1 and 4). The period of evaluation for dose limiting toxicity will be through completion of cycle 1. If ≤1 of the 3 initial patients at the proposed dose experience a DLT, then 3 additional patients will be enrolled for a total of 6 planned patients at that dose level. Otherwise, 3 patients will be enrolled at dose level -1. If ≤ 1 of these patients experience a DLT, then 3 additional patients will be enrolled at the same dose level. If more than 1 patient experiences a DLT in dose level -1, the study will be terminated.

Drug: RO5126766

Interventions

RO5126766 DRUG

RO5126766 (CH5126766) is given 4mg twice weekly (Day 1 and Day 4 of each week) and should be taken by mouth on an empty stomach, either one hour before or two hours after a meal.

Also known as: (CH5126766)

RO5126766 (CH5126766)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven diagnosis of advanced NSCLC
• Documented presence of KRAS mutation
• Prior treatment with a PD-1/L1 inhibitor. Patients who were deemed not eligible for therapy with a PD-1/L1 inhibitor by their treating physician will also be eligible in the dose expansion phase.
• Prior treatment with chemotherapy
• Able to take oral medications
• Measurable and/or evaluable disease (RECIST 1.1) indicator lesion not previously irradiated
• Karnofsky performance status (KPS) ≥ 70% (ECOG of 0 or 1 also acceptable)
• Age≥ 18 years old
• Hematological and biochemical indices within the ranges shown below Hematological and biochemical indices within the ranges shown below (These measurements must be performed within two weeks \[Day 14 to Day 1\] before the patient is entered into the trial).
• AST, ALT ≤ 2.5 x ULN - Total bilirubin ≤ 1.5 x ULN -Albumin≥2.5g/dL
• Creatinine \< 1.5 x ULN OR calculated creatinine clearance ≥50mL/min
• Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3
• Hemoglobin ≥9.0 g/dL
• Platelets ≥100,000/mm\^3.
• A negative serum pregnancy test obtained within two weeks prior to the administration of the study drug in all women of child bearing potential

You may not qualify if:

• Patients with symptomatic brain metastasis requiring escalating doses of steroids
• Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management
• History of any bowel disease including abdominal fistula, gastro-intestinal perforation
• History of acute pancreatitis within 1 year of study entry or history of chronic pancreatitis
• History of or ongoing alcohol abuse that, in the opinion of the treating physician, would compromise compliance or impart excess risks associated with study participation.
• Pregnant or lactating women
• Any type of systemic therapy (chemotherapy or experimental drugs) within 3 weeks of starting treatment on protocol (within 6 weeks for for nitrosoureas and mitomycin C)
• Radiotherapy within 2 weeks of starting treatment on protocol
• Prior treatment with MEK, RAF, or ERK inhibitor(s)
• Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to:
• History of clinically significant (as determined by the treating physician) atrial arrhythmia
• Any ventricular arrhythmia
• History of congenital long QT syndrome.
• Abnormal QTc (≥ 450 msec in males and ≥ 470 msec in females)
• Ejection fraction ≤ 50% as assessed by echocardiogram

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Dana-Farber Cancer Institute: collaborator
• Chugai Pharma USA: collaborator

Study Sites (3)

Miami Cancer Institute

Miami, Florida, 33143, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

RO5126766

Study Officials

• Gregory Riely, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, open label, multi-institution study of RO5126766 (CH5127566) in patients with KRAS mutant NSCLC.

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 24, 2018
• Study Start: October 31, 2018
• Primary Completion: July 8, 2024
• Study Completion: July 8, 2024
• Last Updated: July 10, 2024

Record last verified: 2024-07

Locations

US (3)