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

NCT ID: NCT06228326

Last Updated: 2025-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

250 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-04-17

Study Completion Date

2028-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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Lung Cancer, Non-small Cell Lung Cancer Metastatic Solid Tumor, Adult Advanced Cancer Lung Cancer (NSCLC)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohorts 1 through 4

Dose escalation and expansion cohorts: KB707 monotherapy in subjects with solid tumor malignancies affecting the lungs.

Group Type EXPERIMENTAL

KB707

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

Cohort 5

Dose expansion cohort: KB707 administered in combination with Keytruda in approximately 60 subjects with NSCLC.

Group Type EXPERIMENTAL

KB707

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

PD-1 immune checkpoint inhibitor

Cohort 6

Dose expansion cohort: KB707 administered in combination with Keytruda and chemotherapy in approximately 60 subjects with NSCLC.

Group Type EXPERIMENTAL

KB707

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

Pembrolizumab (KEYTRUDA®)

Intervention Type DRUG

PD-1 immune checkpoint inhibitor

Chemotherapy

Intervention Type DRUG

SOC chemotherapy

Experimental: Cohort 7

Dose expansion cohort: KB707 administered in combination with docetaxel in approximately 50 subjects with NSCLC.

Group Type EXPERIMENTAL

KB707

Intervention Type BIOLOGICAL

Genetically modified herpes simplex type 1 virus

Docetaxel

Intervention Type DRUG

SOC chemotherapy

Interventions

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KB707

Genetically modified herpes simplex type 1 virus

Intervention Type BIOLOGICAL

Pembrolizumab (KEYTRUDA®)

PD-1 immune checkpoint inhibitor

Intervention Type DRUG

Chemotherapy

SOC chemotherapy

Intervention Type DRUG

Docetaxel

SOC chemotherapy

Intervention Type DRUG

Eligibility Criteria

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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.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Krystal Biotech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Chien, MD

Role: STUDY_DIRECTOR

Senior Vice President of Clinical Development

Locations

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XCancer Research Network/Dothan Hematology & Oncology

Dothan, Alabama, United States

Site Status RECRUITING

HonorHealth Research Institute

Scottsdale, Arizona, United States

Site Status RECRUITING

Precision NextGen Oncology

Beverly Hills, California, United States

Site Status RECRUITING

Emad Ibrahim MD Inc

Redlands, California, United States

Site Status RECRUITING

BRCR Global

Weston, Florida, United States

Site Status RECRUITING

IU Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status TERMINATED

Ochsner/MD Anderson Cancer Center

New Orleans, Louisiana, United States

Site Status RECRUITING

Henry Ford Health

Detroit, Michigan, United States

Site Status RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status TERMINATED

Sarah Cannon Research Institute

Nasville, Tennessee, United States

Site Status RECRUITING

Renovatio Clinical

El Paso, Texas, United States

Site Status TERMINATED

Renovatio Clinical

The Woodlands, Texas, United States

Site Status TERMINATED

Countries

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United States

Central Contacts

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David Chien, MD

Role: CONTACT

412-586-5830

Brittani Agostini, RN, CCRC

Role: CONTACT

412-586-5830

Facility Contacts

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Juli Love

Role: primary

334-792-9500

Tony Romero

Role: backup

402-991-8468

Oncology Clinical Trials Nurse Navigator

Role: primary

480-323-1791

Oncology Clinical Trials Nurse Navigator

Role: backup

833-354-6667

Brianna Heaviside

Role: primary

424-777-0708

Ravleen Kaur

Role: backup

424-777-0708

Patricia Ramos, RN

Role: primary

909-478-7973

Katherine Wall

Role: backup

909-478-7973

Vaneska Chacin

Role: primary

561-447-0614 ext. 109

Maria Abreu

Role: backup

561-447-0614 ext. 106

Jill Collins, BA, CCRA

Role: primary

504-842-2466

Amanda Woolery, RN, BSN

Role: backup

504-842-0275

Bethany Adams, RN

Role: primary

313-556-8107

Lisa Lange, RN

Role: backup

313-556-8106

Carrie Smith, RN

Role: primary

330-492-3345

Kim Roby

Role: backup

33-492-3345

Cancer Answer Line

Role: primary

216-444-7923

Sarah Cannon Research Institute

Role: primary

(844) 482-4812

Other Identifiers

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KB707-02

Identifier Type: -

Identifier Source: org_study_id

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