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.
Age 18 years or older at the time of informed consent
Life expectancy >12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Have at least one measurable lung lesion per RECIST v1.1 at Screening
Not fully recovered from prior surgery or radiotherapy, including all radiation-related toxicities
The subject is pregnant, nursing, or plans to become pregnant during study treatment and through three months after the last dose of KB707
Have known history of positive human immunodeficiency virus (HIV 1/2)
Subject has a known additional malignancy that is progressing or requires active treatment
Sequential
KB707
Biological/VaccineGenetically modified herpes simplex type 1 virus
Pembrolizumab (KEYTRUDA®)
DrugPD-1 immune checkpoint inhibitor
Chemotherapy
DrugSOC chemotherapy
Docetaxel
DrugSOC chemotherapy
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
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
To evaluate the preliminary efficacy of inhaled KB707 as determined by overall response rate (ORR)
Percentage of ORR for all participants
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