Clinical trial NCT05970497: A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors
Official title: A Phase 1/2, Open-Label, Multi-Center, Dose Escalation and Expansion Study of KB707 in Subjects With Locally Advanced or Metastatic Solid Tumor Malignancies
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer
Melanoma Stage III
Melanoma Stage IV
Cutaneous Melanoma
Keywords: Krystal Biotech
cancer
melanoma
Lead sponsor: Krystal Biotech, Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-01
Enrollment: 240
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: KB707-01 is a Phase 1/2, open-label, multicenter, dose escalation and expansion study. The study will evaluate the safety and tolerability of KB707 in adults with locally advanced or metastatic solid tumors who have progressed on standard of care therapy, cannot tolerate standard of care therapy, refused standard of care therapy, or for whom there is no standard of care therapy as well as the safety, tolerability, preliminary efficacy, and immunologic effect of KB707 administered in combination with Opdualag to subjects with unresectable or metastatic melanoma.

Subjects in dose escalation (Cohorts 1 through 3) and dose expansion (Cohort 4) will receive intratumoral injections of KB707 approximately every three weeks. Cohorts 1 through 4 are closed to new enrollment. Dose expansion Cohort 5 and Cohort 6 will evaluate subjects with advanced melanoma. Subjects in Cohort 5 will receive intratumoral injections of KB707 biweekly (q2w), delivered in combination with Opdualag (dosed every q4w per prescribing information). Subjects in Cohort 6 will receive intratumoral injections of KB707 biweekly (q2w), delivered in combination with Keytruda (dosed every q6w per prescribing information). All subjects will be treated until disease 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: KB707 is a genetically modified herpes simplex type 1 virus that is designed to stimulate an anti-tumor immune response through the production of cytokines. This is a first-in-human (FIH) clinical study to evaluate the safety and tolerability and preliminary efficacy of KB707 in adult subjects with advanced and/or refractory solid tumors, including advanced melanoma. The study will include a dose escalation portion for single agent KB707 and an expansion portion to further evaluate single agent KB707 at a dose determined by preliminary data in the dose escalation phase as well as combination therapy of KB707 with immune checkpoint inhibitor therapy.

Eligibility criteria: Key Inclusion Criteria:

* Life expectancy \>12 weeks
* ECOG performance status of 0 or 1
* Have measurable disease per RECIST v1.1 at Screening
* Cohorts 1-4 only: Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor and the individual has progressed on standard of care therapy, cannot tolerate standard of care therapy, refused standard of care therapy, or there is no standard of care therapy.
* Cohorts 5 and 6 only: Histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system (8th edition; AJCC 2017) and

  1. Subject has previously failed one prior anti-PD-1/PD-L1 treatment (as monotherapy or in combination with other checkpoint inhibitors such as anti-LAG-3 or anti-CTLA-4); and
  2. If proto-oncogene B-Raf (BRAF) V600 mutation-positive, subject previously failed a BRAF inhibitor or BRAF inhibitor in combination with mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor
* Cohort 5 only: Age 12 years or older at the time of informed consent
* Cohort 6 only: Age 18 years or older at the time of informed consent

Key Exclusion Criteria:

* Prior surgery or radiation therapy must be fully recovered, including all radiation -related toxicities and subject does not require systemic corticosteroids
* 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 uveal/ocular melanoma.
  3. The subject has active brain metastases or leptomeningeal metastases
  4. Subject has received more than 2 lines of systemic therapy for unresectable or metastatic melanoma
  5. Prior anti-LAG-3 and/or anti-PD-1 therapy was intolerable and required discontinuation of treatment

Primary outcomes:
measure: Percentage of adverse events (AEs)
timeFrame: up to 36 months
measure: Percentage of serious adverse events (SAEs)
timeFrame: up to 36 months
Secondary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: up to 36 months
measure: Percentage of overall response rate (ORR)
timeFrame: up to 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Health
state: California
city: Rancho Santa Margarita
country: United States
facility: Mission Dermatology Center
state: California
city: Weston
country: United States
facility: BRCR Global
state: Florida
city: Indianapolis
country: United States
facility: IU Simon Comprehensive Cancer Center
state: Indiana
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Morristown
country: United States
facility: Morristown Medical Center / Atlantic Health System
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine-New York-Presbyterian Hospital
state: New York
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 - El Paso
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical - The Woodlands
state: Texas
Study officials:
affiliation: Senior Vice President of Clinical Development
name: David Chien, MD
role: STUDY_DIRECTOR
References: