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NCT06228326PHASE1, PHASE2Recruiting

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

Krystal Biotech, Inc.

Start Date

4/17/2024

Completion Date

7/1/2028

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: * 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, 6, and 7 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: 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, 6, and 7 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

Interventions

BIOLOGICAL

KB707

DRUG

Pembrolizumab (KEYTRUDA®)

DRUG

Chemotherapy

DRUG

Docetaxel

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Conditions

Lung Cancer, Non-small CellLung Cancer MetastaticSolid Tumor, AdultAdvanced CancerLung Cancer (NSCLC)

Locations

XCancer Research Network/Dothan Hematology & Oncology

Dothan, Alabama 36303

United States

HonorHealth Research Institute

Scottsdale, Arizona 85258

United States

Precision NextGen Oncology

Beverly Hills, California 90212

United States

Emad Ibrahim MD Inc

Redlands, California 92373

United States

BRCR Global

Weston, Florida 33326

United States

IU Simon Comprehensive Cancer Center

Indianapolis, Indiana 46202

United States

Ochsner/MD Anderson Cancer Center

New Orleans, Louisiana 70121

United States

Henry Ford Health

Detroit, Michigan 48202

United States

Gabrail Cancer Center Research

Canton, Ohio 44718

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Sarah Cannon Research Institute

Nasville, Tennessee 37203

United States

Renovatio Clinical

El Paso, Texas 79915

United States

Renovatio Clinical

The Woodlands, Texas 77380

United States