A Phase I/Ib Open-Label, Multi-Center, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of Intravenous NBF 006 in Patients With Non-Small Cell Lung, Pancreatic, or Colorectal Cancer Followed by a Dose Expansion Study in Patients With KRAS-Mutated Non-Small Cell Lung Cancer

Nitto BioPharma, Inc.9 sites in 1 country49 target enrollmentMarch 18, 2019

ConditionsNon-Small Cell Lung Cancer Pancreatic Cancer Colorectal Cancer

InterventionsNBF-006

DrugsNBF-006

Overview

Phase: Phase 1
Intervention: NBF-006
Conditions: Non-Small Cell Lung Cancer
Sponsor: Nitto BioPharma, Inc.
Enrollment: 49
Locations: 9
Primary Endpoint: Number of patients with treatment-related adverse events as assessed by CTCAE v5.0
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, non-controlled study conducted in two parts - Part A (dose escalation) followed by Part B (dose expansion).

Detailed Description

Patients in Part A will have previously treated progressive or metastatic NSCLC, pancreatic, or colorectal cancer, with or without KRAS mutation. Five dose levels will be explored. In dose level 5, only patients with previously-treated NSCLC with KRAS mutation will be included. Patients in Part B must have previously treated NSCLC with confirmed KRAS mutation. Two dose levels will be explored further in Part B. Twenty (20) patients will be enrolled in Part B, with 10 patients enrolled in each of the two cohorts. Once dose level 5 has been confirmed to be safe in Part A (i.e. 0-1 DLT in 6 patients), an additional 4 patients will then be enrolled for a planned total of 24 patients in Part B.

Registry

clinicaltrials.gov

Start Date

March 18, 2019

End Date

March 12, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Nitto BioPharma, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Part A: Patients with histologically or cytologically confirmed progressive or metastatic NSCLC, pancreatic, or colorectal cancer that have failed standard treatment and for which no other effective treatment is available or appropriate for the patient up to dose level
•In dose level 5, patients with histologically or cytologically confirmed progressive or metastatic NSCLC with documented KRAS-mutant genotype, who have failed standard treatment and have no other effective treatment available or appropriate for the patient.
•Part B: Patients with histologically or cytologically confirmed progressive or metastatic NSCLC with documented KRAS-mutant genotype, who have failed standard treatment and have no other effective treatment available or appropriate for the patient.
•Eastern Cooperative Oncology Group performance status of 0-
•Men and women ≥ 18 years of age.
•Patients must have recovered from all acute adverse effects (excluding alopecia) of prior therapies to baseline or ≤ Grade 1 prior to study entry.
•Adequate bone marrow function, defined as an absolute neutrophil count (ANC) ≥ 1.5 x 109/L and a platelet count ≥ 100 x 109/L.
•Adequate renal function, defined as serum creatinine ≤ 1.5 x upper limit of normal (ULN) for the institution or calculated creatinine clearance \[Cockcroft-Gault method\] must be ≥ 60 mL/min/1.73 m². If serum creatinine is \>1.5 x ULN, then creatinine clearance can be calculated from a 24-hour urine collection.
•Adequate hepatic function, defined as total bilirubin ≤ 1.5 mg/dL and alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 x ULN, or ≤ 5 x ULN if known liver metastases.
•Female patients of childbearing potential must have a negative serum or urine pregnancy test result at time of pre-treatment screening.

Exclusion Criteria

•Prior chemotherapy, radiation therapy, or investigational therapy within 4 weeks (exception: 6 weeks for nitrosoureas or mitomycin C); or prior non-cytotoxic therapy within 5 drug half-lives (or 4 weeks, whichever is shorter); or monoclonal antibodies within 4 weeks prior to the first dose of study treatment.
•Concurrent use of any other investigational agent.
•Known or clinically suspected central nervous system or leptomeningeal metastases, unless irradiated or treated a minimum of 4 weeks prior to first study treatment and stable without requirement of corticosteroids for \> 1 week.
•Pregnant or breast feeding. A negative pregnancy test must be documented at baseline for women of childbearing potential. Patients may not breast-feed infants while on this study.
•Significant cardiovascular disease or condition, including:
•Congestive heart failure currently requiring therapy
•Need for antiarrhythmic medical therapy for ventricular arrhythmia
•Severe conduction disturbance
•Angina pectoris requiring therapy
•QTc interval \> 450 msec (males) or \> 470 msec (females) Fridericia's correction.

Arms & Interventions

NBF-006

Intervention: NBF-006

Outcomes

Primary Outcomes

Number of patients with treatment-related adverse events as assessed by CTCAE v5.0

Time Frame: Change in the incidence and severity of adverse events related to study treatment from baseline to 4 weeks following last dose

Secondary Outcomes

Pharmacokinetic parameters for siRNA(Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1)
Best Overall Response per RECIST 1.1(Number of days from date of first dose to 30 days after last treatment)
Additional pharmacokinetic parameters for siRNA(Up to 72 hours from start of infusion on Cycle 1, Day 1 and Day 22 and prior to infusion Cycle 1, Day 8 and Cycle 2, Day 1)