KB707-02: a Phase I/II Study of Inhaled KB707 in Patients with Advanced Solid Tumor Malignancies Affecting the Lungs
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Study Summary
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. To evaluate whether KB707 administered by inhalation will deliver efficacious dose to the lung while minimizing systemic exposure in advanced solid tumor patients with predominantly lung disease. Immunologic biomarkers were assessed.
Main objective:
To evaluate the safety and tolerability of inhaled KB707 monotherapy and in combination regimens (e.g., KB707 plus immune checkpoint inhibitors [with or without chemotherapy]; or docetaxel)
- 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 Cohorts 1 through 4 only: Histologically confirmed diagnosis of advanced solid tumor malignancy affecting the lungs and the individual has progressed on standard of care therapy, cannot tolerate standard of care therapy, refused standard of care therapy, or has no standard of care therapy. Cohorts 5 and 6 only: (1) Histologically or cytologically confirmed diagnosis of stage 3 or 4 NSCLC, as per American Joint Committee on Cancer (AJCC) staging system (8th edition) and (2) Subject must meet the following criteria of prior lines of therapy: 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. 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.
- As per CTIS:
- 1. The subject or legally authorized representative must have read, understood, and signed an Institutional Review Board (IRB) approved Informed Consent Form and must be willing and able to comply with study procedures and instructions.
- 2. Age 18 years or older at the time of informed consent.
- 3. Life expectancy >12 weeks.
- 4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening
- 5. Have at least one measurable lung lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at Screening.
- 6. Demonstrated adequate organ function at Screening, as defined below: a. WBC count ≥2000/μL (after at least 7 days without growth factor support) b. Absolute neutrophil count ≥1500/μL (after at least 7 days without growth factor support) c. Platelet count ≥100×103 μL d. Hemoglobin ≥9.0 g/dL e. Serum creatinine ≤2 mg/dL (or glomerular filtration rate ≥40 mL/min) f. AST and ALT ≤3x upper limit of normal (ULN)g. Total bilirubin within normal limits unless associated with hepatobiliary metastases or Gilbert’s syndrome, in that case total bilirubin ≤2x ULN
- 7. Histologically confirmed diagnosis of advanced solid tumor malignancy affecting the lungs and the individual has progressed on standard of care therapy, cannot tolerate standard of care therapy, refused standard of care therapy, or has no standard of care therapy.
- 8. Histologically or cytologically confirmed diagnosis of stage 3 or 4 NSCLC, as per American Joint Committee on Cancer (AJCC) staging system (8th edition)
- 9. Subject must meet the following criteria of prior lines of therapy: a. 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. b. 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.
- 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: Subject has a known additional malignancy that is progressing or requires active treatment Subject has active brain metastases or leptomeningeal metastases Prior anti-PD-1/PD-L1 therapy was intolerable and required discontinuation of treatment Subject has active, known, or suspected autoimmune disease requiring systemic treatment Subject has known acute or chronic hepatitis Subject has active pneumonitis or history of ICI-induced pneumonitis that required steroids
- As per CTIS:
- 1. Not fully recovered from prior surgery or radiotherapy, including all radiation-related toxicities.
- 2. Have known medical history of positive test for, or diagnosis of, human immunodeficiency virus (HIV-1/2).
- 3. The subject is pregnant, nursing, or plans to become pregnant during study treatment and through three months after the last dose of KB707.
- 4. Subject who is unwilling to comply with contraception requirements per-protocol.
- 5. Any clinical condition or clinically significant abnormality that, in the opinion of the Investigator, would impact a subject’s ability to complete all study-related procedures and/or poses an additional risk to the assessment of safety of KB707.
- 6. Subject is known to be noncompliant or is unlikely to comply with the requirements of the study protocol in the opinion of the Investigator.
- 7. Subject has a known additional malignancy that is progressing or requires active treatment.
- 8. Subject has active brain metastases or leptomeningeal metastases.
- 9. Prior anti-PD-1/PD-L1 therapy was intolerable and required discontinuation of treatment.
Clinical Study Information for Healthcare Providers
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