A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs
- Conditions
- Lung Cancer, Non-small CellLung Cancer MetastaticSolid Tumor, AdultAdvanced CancerLung Cancer (NSCLC)
- Interventions
- Registration Number
- NCT06228326
- Lead Sponsor
- Krystal Biotech, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 140
- 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
Key
- 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 active brain metastases or leptomeningeal metastases
- Subject has a known additional malignancy that is progressing or requires active treatment
- Prior anti-PD-1/PD-L1 therapy was intolerable and required discontinuation of treatment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation of KB707 Administered via Nebulization KB707 Dose escalation of single-agent KB707 in 3 cohorts in a standard 3+3 design. Dose Expansion of KB707 Administered in Combination with Keytruda KB707 Dose expansion cohort: KB707 administered in combination with Keytruda in approximately 60 subjects with NSCLC. Dose Expansion of KB707 Administered in Combination with Keytruda Pembrolizumab (KEYTRUDA®) Dose expansion cohort: KB707 administered in combination with Keytruda in approximately 60 subjects with NSCLC. Dose Expansion of KB707 Administered in Combination with Keytruda and Chemotherapy KB707 Dose expansion cohort: KB707 administered in combination with Keytruda and chemotherapy in approximately 60 subjects with NSCLC. Dose Expansion of KB707 Administered in Combination with Keytruda and Chemotherapy Pembrolizumab (KEYTRUDA®) Dose expansion cohort: KB707 administered in combination with Keytruda and chemotherapy in approximately 60 subjects with NSCLC. Dose Expansion of KB707 Administered in Combination with Keytruda and Chemotherapy Chemotherapy Dose expansion cohort: KB707 administered in combination with Keytruda and chemotherapy in approximately 60 subjects with NSCLC.
- Primary Outcome Measures
Name Time Method To evaluate the safety and tolerability of inhaled KB707 based upon assessment of adverse events (AE) up to 36 months Percentage of subjects with treatment-related AEs as assessed by NCI-CTCAE v5
- Secondary Outcome Measures
Name Time Method To evaluate the preliminary efficacy of inhaled KB707 as determined by overall response rate (ORR) up to 36 months Percentage of ORR for all participants
To evaluate whether the proposed dose ranges include the maximum tolerated dose of KB707 as determined by incidence of dose limiting toxicities (DLTs) up to 36 months Incidence of dose limiting toxicity (DLT) by dose cohorts
Trial Locations
- Locations (7)
HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States
IU Simon Comprehensive Cancer Center
🇺🇸Indianapolis, Indiana, United States
Ochsner/MD Anderson Cancer Center
🇺🇸New Orleans, Louisiana, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nasville, Tennessee, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States