A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors

Phase 1

Recruiting

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 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). 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 KB707 at a dose determined by preliminary data in the dose escalation phase.

Recruitment & Eligibility

Inclusion Criteria

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.
Age 12 years or older at the time of informed consent
Life expectancy >12 weeks
ECOG performance status of 0 or 1
Have measurable disease per RECIST v1.1 at Screening
Histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system (8th edition; AJCC 2017)

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)
The subject must not have active brain metastases or leptomeningeal metastases
Subject has a known additional malignancy that is progressing or requires active treatment.
Prior anti-LAG-3/anti-PD-1 therapy was intolerable and required discontinuation of treatment
Subject has uveal/ocular melanoma

Arm && Interventions

Group	Intervention	Description
Dose escalation of KB707 by intratumoral (IT) injection in solid tumors	KB707	Dose escalation of single-agent KB707 in 3 cohorts to treat superficial solid tumors
Dose expansion: KB707 in Combination with Opdualag (in patients with advanced melanoma)	KB707	Dose expansion cohort: KB707 administered in combination with Opdualag in approximately 100 subjects with advanced melanoma.
Dose expansion: KB707 in Combination with Opdualag (in patients with advanced melanoma)	Opdualag	Dose expansion cohort: KB707 administered in combination with Opdualag in approximately 100 subjects with advanced melanoma.

Primary Outcome Measures

Name	Time	Method
Percentage of adverse events (AEs)	up to 36 months	Percentage of subjects with adverse events (AEs)
Percentage of serious adverse events (SAEs)	up to 36 months	Percentage of subjects with serious adverse events (SAEs)

Secondary Outcome Measures

Name	Time	Method
Percentage of overall response rate (ORR)	up to 36 months	Percentage of ORR
Maximum tolerated dose (MTD)	up to 36 months	Assess whether the tested doses include the maximum tolerated dose (MTD) of KB707 based on the safety and response data collected during the dose escalation portion of the study

Locations (14): UCLA Health
🇺🇸
Los Angeles, California, United States
Stanford Cancer Center
🇺🇸
Palo Alto, California, United States
Mission Dermatology Center
🇺🇸
Rancho Santa Margarita, California, United States
IU Simon Comprehensive Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Henry Ford Cancer Institute
🇺🇸
Detroit, Michigan, United States
Morristown Medical Center / Atlantic Health System
🇺🇸
Morristown, New Jersey, United States
Weill Cornell Medicine-New York-Presbyterian Hospital
🇺🇸
New York, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
UPMC Hillman Cancer Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Renovatio Clinical - El Paso
🇺🇸
El Paso, Texas, United States
MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Renovatio Clinical - The Woodlands
🇺🇸
The Woodlands, Texas, United States