The Sponsor is developing KB707, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector designed to stimulate an anti-tumor immune response through the production of cytokines within the local tumor microenvironment in the lungs. KB707 is administered via nebulization, delivering the therapy directly through the airways to the lungs of subjects with advanced solid tumor malignancies. This is a Phase 1/2, open-label, multicenter, dose escalation and expansion study designed to evaluate the safety, tolerability, preliminary efficacy, and immunologic effect of KB707. Monotherapy KB707 dose escalation and expansion cohorts enrolled adults with advanced solid tumor malignancies affecting the lungs who had progressed on standard of care therapy, cannot tolerate standard of care therapy, or refused standard of care therapy. The dose escalation phase (Cohorts 1 and 2) evaluated KB707 monotherapy using a standard 3+3 design, followed by a dose expansion phase (Cohort 4) to further evaluate the selected dose. Subjects received inhaled KB707 weekly for three weeks, then every three weeks. The dose escalation portion of the study is now complete, and the selected dose is being evaluated in the expansion phase. Combination regimens with a selected (fixed) dose of KB707 are being evaluated in subjects with advanced or metastatic non-small cell lung cancer (NSCLC). Subjects in Cohorts 5 and 6 are receiving inhaled KB707 once every 2 weeks (q2w), delivered in combination with Keytruda once every 6 weeks. Subjects in Cohort 7 are receiving inhaled KB707 in combination with docetaxel once every 3 weeks. All subjects will be treated until tumor progression, death, unacceptable toxicity, symptomatic deterioration, achievement of maximal response, subject choice, Investigator decision to discontinue treatment, or the Sponsor determines to terminate the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
250
Genetically modified herpes simplex type 1 virus
PD-1 immune checkpoint inhibitor
SOC chemotherapy
SOC chemotherapy
XCancer Research Network/Dothan Hematology & Oncology
Dothan, Alabama, United States
RECRUITINGHonorHealth Research Institute
Scottsdale, Arizona, United States
RECRUITINGPrecision NextGen Oncology
Beverly Hills, California, United States
RECRUITINGEmad Ibrahim MD Inc
Redlands, California, United States
RECRUITINGBRCR Global
Weston, Florida, United States
RECRUITINGIU Simon Comprehensive Cancer Center
Indianapolis, Indiana, United States
TERMINATEDOchsner/MD Anderson Cancer Center
New Orleans, Louisiana, United States
RECRUITINGHenry Ford Health
Detroit, Michigan, United States
RECRUITINGGabrail Cancer Center Research
Canton, Ohio, United States
RECRUITINGCleveland Clinic
Cleveland, Ohio, United States
RECRUITING...and 4 more locations
To evaluate the safety and tolerability of inhaled KB707 based upon assessment of adverse events (AE)
Percentage of subjects with treatment-related AEs as assessed by NCI-CTCAE v5
Time frame: up to 36 months
To evaluate whether the proposed dose ranges include the maximum tolerated dose of KB707 as determined by incidence of dose limiting toxicities (DLTs)
Incidence of dose limiting toxicity (DLT) by dose cohorts
Time frame: up to 36 months
To evaluate the preliminary efficacy of inhaled KB707 as determined by overall response rate (ORR)
Percentage of ORR for all participants
Time frame: up to 36 months
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