NCT06228326

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
250

participants targeted

Target at P75+ for phase_1

Timeline
26mo left

Started Apr 2024

Longer than P75 for phase_1

Geographic Reach
1 country

14 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress49%
Apr 2024Jul 2028

First Submitted

Initial submission to the registry

January 18, 2024

Completed
11 days until next milestone

First Posted

Study publicly available on registry

January 29, 2024

Completed
3 months until next milestone

Study Start

First participant enrolled

April 17, 2024

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected
1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2028

Last Updated

October 24, 2025

Status Verified

October 1, 2025

Enrollment Period

2.8 years

First QC Date

January 18, 2024

Last Update Submit

October 22, 2025

Conditions

Keywords

cancerKrystal Biotechlung cancer

Outcome Measures

Primary Outcomes (1)

  • To evaluate the safety and tolerability of inhaled KB707 based upon assessment of adverse events (AE)

    Percentage of subjects with treatment-related AEs as assessed by NCI-CTCAE v5

    up to 36 months

Secondary Outcomes (2)

  • 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

  • To evaluate the preliminary efficacy of inhaled KB707 as determined by overall response rate (ORR)

    up to 36 months

Study Arms (4)

Cohorts 1 through 4

EXPERIMENTAL

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

Biological: KB707

Cohort 5

EXPERIMENTAL

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

Biological: KB707Drug: Pembrolizumab (KEYTRUDA®)

Cohort 6

EXPERIMENTAL

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

Biological: KB707Drug: Pembrolizumab (KEYTRUDA®)Drug: Chemotherapy

Experimental: Cohort 7

EXPERIMENTAL

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

Biological: KB707Drug: Docetaxel

Interventions

KB707BIOLOGICAL

Genetically modified herpes simplex type 1 virus

Cohort 5Cohort 6Cohorts 1 through 4Experimental: Cohort 7

PD-1 immune checkpoint inhibitor

Cohort 5Cohort 6

SOC chemotherapy

Cohort 6

SOC chemotherapy

Experimental: Cohort 7

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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.

You may not qualify if:

  • 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:
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

XCancer Research Network/Dothan Hematology & Oncology

Dothan, Alabama, 36303, United States

RECRUITING

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

Precision NextGen Oncology

Beverly Hills, California, 90212, United States

RECRUITING

Emad Ibrahim MD Inc

Redlands, California, 92373, United States

RECRUITING

BRCR Global

Weston, Florida, 33326, United States

RECRUITING

IU Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

TERMINATED

Ochsner/MD Anderson Cancer Center

New Orleans, Louisiana, 70121, United States

RECRUITING

Henry Ford Health

Detroit, Michigan, 48202, United States

RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

TERMINATED

Sarah Cannon Research Institute

Nasville, Tennessee, 37203, United States

RECRUITING

Renovatio Clinical

El Paso, Texas, 79915, United States

TERMINATED

Renovatio Clinical

The Woodlands, Texas, 77380, United States

TERMINATED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungLung NeoplasmsNeoplasms

Interventions

pembrolizumabDrug TherapyDocetaxel

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

TherapeuticsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenes

Study Officials

  • David Chien, MD

    Senior Vice President of Clinical Development

    STUDY DIRECTOR

Central Study Contacts

David Chien, MD

CONTACT

Brittani Agostini, RN, CCRC

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 18, 2024

First Posted

January 29, 2024

Study Start

April 17, 2024

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

July 1, 2028

Last Updated

October 24, 2025

Record last verified: 2025-10

Locations