Clinical trial NCT04446351: Study of the Safety and Effectiveness of GSK6097608 in Participants With Advanced Solid Tumors
Official title: A Phase 1 First-Time-in-Human, Open-Label Study of GSK6097608 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Keywords: GSK6097608
dostarlimab
Dose escalation
Pharmacokinetics
Pharmacodynamics
Advanced solid tumors
First-time-in-human
GSK4428859A
EOS884448
cobolimab
belrestotug
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: 23andMe, Inc.
name: iTeos Therapeutics
First posted: 2020-06-24
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Participants will receive treatment in different dose escalation arms of the study.
Primary purpose: TREATMENT

Brief summary: This first-time-in-human (FTIH) study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of escalating doses of GSK6097608 given as monotherapy and in combination with dostarlimab in participants with advanced solid tumors. In addition, dostarlimab will be given as monotherapy (Arm D); and in combination with belrestotug (Arm E); and with GSK6097608 + belrestotug (Arm F) in Japanese and Chinese participants. The study may assess the PK/PD cohorts for Arm E and/or Arm F in participants outside of China and Japan. Additionally, dostarlimab will be given in combination with cobolimab in Japanese participants. Drug name mentioned as belrestotug, GSK4428859A and EOS884448 are interchangeable for the same compound. In the rest of the document, the drug will be referred to as belrestotug.


Eligibility criteria: Inclusion Criteria:

* Adults 18 years of age or older (or \>=20 years of age in Arm-A Japan, Arm-D Japan, Arm E-Japan, Arm F-Japan, and Arm G-Japan)
* Female participants of childbearing potential must agree to use a highly effective form of contraception
* Histological or cytological documentation of locally advanced, recurrent, or metastatic solid malignancy. Enrollment in PK/PD cohorts will be restricted to participants with histologically or cytologically confirmed diagnosis of 1 or more of the following: non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), endometrial cancer (EC), colorectal cancer (CRC) (including specified molecular subtypes of these) or an alternative immunogenic tumor type with medical monitor approval
* Disease that has progressed after standard therapy for the specific tumor type, or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate, or if no further standard therapy exists
* Participants in a PK/PD cohort (Arms A, B, E and F) must provide fresh tumor biopsies. Biopsies are not required from participants enrolled in Arm D, Arm E, (non-PK/PD cohorts only), Arm F (non-PK/PD cohort only), Arm G or any participant enrolled in mainland China
* Eastern cooperative oncology group (ECOG) performance status (PS) 0 to 1
* Life expectancy of at least 12 weeks
* Adequate organ function as determined by laboratory assessments
* Adequate cardiac ejection fraction as measured by echocardiogram
* Arm A-Japan, Arm D-Japan, Arm E-Japan, Arm F-Japan, and Arm G-Japan only: lives in Japan and is racially Japanese, defined as all biological grandparents being Japanese
* Arm A-China, Arm B-China, Arm D-China, Arm E-China and Arm F-China only (excluding PK/PD cohorts in Arm E and Arm F): is of Chinese descent and lives in China
* Arm D, Arm E, Arm F, and Arm G only: has been deemed suitable for assigned treatment based on assessment by the investigator

Exclusion Criteria:

* Prior anti-cancer treatment including investigational agents, immune checkpoint inhibitors, chemotherapy, targeted therapy, and biological therapy: within 4 weeks or 5 half-lives of the drug, whichever is shorter
* Prior allogenic or autologous bone marrow transplantation or other solid organ transplantation
* Toxicity from previous anticancer treatment, including; greater than or equal to (\>=) Grade 3 immune-mediated toxicity considered related to prior immunotherapy and that led to treatment discontinuation; or toxicity related to prior treatment that has not resolved; or history of myocarditis of any grade during a previous treatment with immunotherapy
* Known additional malignancy that progressed or required active treatment within the last 2 years
* Uncontrolled or symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis
* Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years
* Concurrent medical condition requiring the use of systemic immunosuppressive treatment
* Cirrhosis or current unstable liver or biliary disease per investigator assessment
* Active infection requiring systemic treatment, known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
* Prolonged QT as measured by electrocardiogram
* Allergen desensitization therapy within 4 weeks of starting study intervention
* History of hypersensitivity to any of the study interventions or their excipients
* Has a history or evidence of cardiac abnormalities within the 6 months prior to enrolment
* Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions
* History of idiopathic pulmonary fibrosis; interstitial lung disease; organizing pneumonia; noninfectious pneumonitis that required steroids, or evidence of active, noninfectious pneumonitis
* Pregnant or lactating woman
* Receipt of live vaccine within 30 days of the start of study intervention
* Receipt of transfusion of blood products or administration of colony-stimulating factors within 14 days before the first dose of study intervention
* Major surgery less than 4 weeks before the first dose of study intervention
* Known drug or alcohol abuse

Primary outcomes:
measure: Number of participants with dose-limiting toxicities (DLTs)
timeFrame: Up to Day 21
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Number of participants with clinically significant changes in laboratory parameters, vital signs, and 12-lead electrocardiogram (ECG) findings
timeFrame: Up to 2 years
measure: Number of participants with dose reductions or delay
timeFrame: Up to 2 years
measure: Number of participants withdrawn due to AEs
timeFrame: Up to 2 years
measure: Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
timeFrame: Up to 2 years
measure: Arms D, E, F, G: ORR based on modified Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: Up to 2 years
measure: Arms D, E, F, G: Disease Control Rate (DCR) based on RECIST 1.1
timeFrame: Up to 2 years
measure: Arms D, E, F, G: DCR based on iRECIST
timeFrame: Up to 2 years
measure: Arms D, E, F, G: Time to response (TTR) based on RECIST 1.1
timeFrame: Up to 2 years
measure: Arms D, E, F, G: TTR based on iRECIST
timeFrame: Up to 2 years
measure: Arms D, E, F, G: Duration of response (DOR) based on RECIST 1.1
timeFrame: Up to 2 years
measure: Arms D, E, F, G: DOR based on iRECIST
timeFrame: Up to 2 years
measure: Arms D, E, F, G: Progression-free survival (PFS) based on RECIST 1.1
timeFrame: Up to 2 years
measure: Arms D, E, F, G: PFS based on iRECIST
timeFrame: Up to 2 years
measure: Arms A, B, F: Number of participants with positive anti-drug antibodies (ADAs) against GSK6097608
timeFrame: Up to 2 years
measure: Arms A, B, F: Titers of ADAs against GSK6097608
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: Number of participants with positive ADAs against dostarlimab
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: Titers of ADAs against dostarlimab
timeFrame: Up to 2 years
measure: Arms E, F: Number of participants with positive ADAs against belrestotug
timeFrame: Up to 2 years
measure: Arms E, F: Titers of ADAs against belrestotug
timeFrame: Up to 2 years
measure: Arm G: Number of participants with positive ADAs against cobolimab
timeFrame: Up to 2 years
measure: Arm G: Titers of ADAs against cobolimab
timeFrame: Up to 2 years
measure: Arms A, B, F: Maximum observed concentration (Cmax) for GSK6097608
timeFrame: Up to 2 years
measure: Arms A, B, F: Minimum observed concentration (Cmin) for GSK6097608
timeFrame: Up to 2 years
measure: Arms A, B, F: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC[0-infinity]) for GSK6097608
timeFrame: Up to 2 years
measure: Arms A, B, F: Area under the plasma concentration-time curve from time zero to time (AUC[0-t]) for GSK6097608
timeFrame: Up to 2 years
measure: Arms A, B, F: Apparent terminal phase half-life (t1/2) for GSK6097608
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: Cmax for dostarlimab
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: Cmin for dostarlimab
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: AUC(0-infinity) for dostarlimab
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: AUC(0-t) for dostarlimab
timeFrame: Up to 2 years
measure: Arms B, D, E, F, G: t1/2 for dostarlimab
timeFrame: Up to 2 years
measure: Arms E, F: Cmax for belrestotug
timeFrame: Up to 2 years
measure: Arms E, F: Cmin for belrestotug
timeFrame: Up to 2 years
measure: Arms E, F: AUC(0-infinity) for belrestotug
timeFrame: Up to 2 years
measure: Arms E, F: AUC(0-t) for belrestotug
timeFrame: Up to 2 years
measure: Arms E, F: t1/2 for belrestotug
timeFrame: Up to 2 years
measure: Arm G: Cmax for cobolimab
timeFrame: Up to 2 years
measure: Arm G: Cmin for cobolimab
timeFrame: Up to 2 years
measure: Arm G: AUC(0-infinity) for cobolimab
timeFrame: Up to 2 years
measure: Arm G: AUC(0-t) for cobolimab
timeFrame: Up to 2 years
measure: Arm G: t1/2 for cobolimab
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: