Clinical trial NCT06228326: A Study Assessing KB707 for the Treatment of Advanced Solid Tumor Malignancies Affecting the Lungs
Official title: KB707-02: A Phase 1/2 Study of Inhaled KB707 in Patients With Advanced Solid Tumor Malignancies Affecting the Lungs
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lung Cancer, Non-small Cell
Lung Cancer Metastatic
Solid Tumor, Adult
Advanced Cancer
Lung Cancer (NSCLC)
Keywords: cancer
Krystal Biotech
lung cancer
Lead sponsor: Krystal Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2024-01-29
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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:

  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 and 6 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

Primary outcomes:
measure: To evaluate the safety and tolerability of inhaled KB707 based upon assessment of adverse events (AE)
timeFrame: up to 36 months
Secondary outcomes:
measure: To evaluate whether the proposed dose ranges include the maximum tolerated dose of KB707 as determined by incidence of dose limiting toxicities (DLTs)
timeFrame: up to 36 months
measure: To evaluate the preliminary efficacy of inhaled KB707 as determined by overall response rate (ORR)
timeFrame: up to 36 months
Other outcomes:
Locations:
city: Dothan
country: United States
facility: XCancer Research Network/Dothan Hematology & Oncology
state: Alabama
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Weston
country: United States
facility: BRCR Global
state: Florida
city: Indianapolis
country: United States
facility: IU Simon Comprehensive Cancer Center
state: Indiana
city: New Orleans
country: United States
facility: Ochsner/MD Anderson Cancer Center
state: Louisiana
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: El Paso
country: United States
facility: Renovatio Clinical
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
Study officials:
affiliation: Senior Vice President of Clinical Development
name: David Chien, MD
role: STUDY_DIRECTOR
References: