A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs

The Sponsor is developing KB707, a replication-defective, non-integrating herpes simplex virus type 1 (HSV-1)-derived vector that is designed to stimulate an anti-tumor immune response through the production of cytokines delivered to the airways of people with advanced solid tumor malignancies affecting the lungs via nebulization. This Phase 1/2, open-label, multicenter, dose escalation and expansion study is designed to evaluate the safety and tolerability of KB707 in adults with with advanced solid tumor malignancies affecting the lungs who have progressed on standard of care therapy, cannot tolerate standard of care therapy, or refused standard of care therapy, as well as the safety, tolerability, preliminary efficacy, and immunologic effect of KB707 administered in combination with Keytruda, with or without chemotherapy, to subjects with advanced NSCLC. The study will include a dose escalation portion for single agent KB707 using a standard 3+3 design followed by a dose expansion portion to further evaluate single agent KB707 at a dose determined by preliminary data in the dose escalation phase. Subjects in the dose escalation (Cohorts 1 and 2) and dose expansion (Cohort 4) will receive KB707 via nebulization weekly for three weeks, then every three weeks. The dose escalation portion of the study has now closed, and the Cohort 2 dose was selected for evaluation in dose expansion.

Dose expansion Cohorts 5 and 6 will evaluate subjects with advanced non-small cell lung cancer (NSCLC). Subjects in Cohorts 5 and 6 will receive inhaled KB707 per treatment day once every 2 weeks (q2w), delivered in combination with Keytruda (once every 6 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.


Eligibility Criteria:
Key Inclusion Criteria:

* Histologically or cytologically confirmed diagnosis of stage 3 or 4 NSCLC, as per American Joint Committee on Cancer (AJCC) staging system (8th edition).
* 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
* Subject is receiving Keytruda or eligible to receive Keytruda
* Cohorts 5 and 6 only: Histologically or cytologically confirmed diagnosis of stage 3 or 4 NSCLC, as per American Joint Committee on Cancer (AJCC) staging system (8th edition) and
* Subject must meet the following criteria of prior lines of therapy:

  1. Subject has previously received no more than one line of prior immune checkpoint inhibitor (ICI) with or without platinum-based chemotherapy, or no more than two prior lines of therapy when given the ICI and platinum-based chemotherapy sequentially as two separate lines.
  2. Subjects with an actionable mutation (e.g., EGFR, KRAS, ALK, or ROS1 genomic alteration), are permitted to have received one additional line of approved targeted therapy.

Key Exclusion Criteria:

* 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)
* Cohorts 5 and 6 only:

  1. Subject has a known additional malignancy that is progressing or requires active treatment
  2. Subject has active brain metastases or leptomeningeal metastases
  3. Prior anti-PD-1/PD-L1 therapy was intolerable and required discontinuation of treatment
  4. Subject has active, known, or suspected autoimmune disease requiring systemic treatment
  5. Subject has known acute or chronic hepatitis
  6. Subject has active pneumonitis or history of ICI-induced pneumonitis that required steroids