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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05277051




Registration number
NCT05277051
Ethics application status
Date submitted
3/03/2022
Date registered
14/03/2022
Date last updated
11/01/2024

Titles & IDs
Public title
First-Time-in-Human Study of GSK4381562 in Participants With Advanced Solid Tumors
Scientific title
A Phase 1 First-Time-in-Human, Open-Label Study of GSK4381562 Administered as Monotherapy and in Combination With Anticancer Agents in Participants With Selected Advanced Solid Tumors
Secondary ID [1] 0 0
2021-004968-95
Secondary ID [2] 0 0
217228
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK4381562
Treatment: Drugs - Dostarlimab
Treatment: Drugs - GSK4428859A

Experimental: Participants receiving GSK4381562 monotherapy (Arm A) -

Experimental: Participants receiving GSK4381562 plus dostarlimab (Arm B) -

Experimental: Participants receiving GSK4381562 plus dostarlimab plus GSK4428859A (Arm C) -

Experimental: Participants receiving dostarlimab plus GSK4428859A (Arm D) -


Treatment: Drugs: GSK4381562
GSK4381562 will be administered.

Treatment: Drugs: Dostarlimab
Dostarlimab will be administered.

Treatment: Drugs: GSK4428859A
GSK4428859A will be administered.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Arms A, B, C: Number of participants with dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 21 days
Primary outcome [2] 0 0
Arms A, B, C, D: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timepoint [2] 0 0
Up to 27 months
Secondary outcome [1] 0 0
Number of participants with clinically significant changes in laboratory parameters, electrocardiogram (ECG) and vital signs
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Number of participants with dose reductions or delays
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
Number of participants with withdrawals due to AEs
Timepoint [3] 0 0
Up to 27 months
Secondary outcome [4] 0 0
Overall response rate (ORR)
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Number of participants with positive antidrug antibodies (ADA) to GSK4381562
Timepoint [5] 0 0
Up to 27 months
Secondary outcome [6] 0 0
Titers of ADA to GSK4381562
Timepoint [6] 0 0
Up to 27 months
Secondary outcome [7] 0 0
Number of participants with positive ADA to dostarlimab
Timepoint [7] 0 0
Up to 27 months
Secondary outcome [8] 0 0
Titers of ADA to dostarlimab
Timepoint [8] 0 0
Up to 27 months
Secondary outcome [9] 0 0
Number of participants with positive ADA to GSK4428859A
Timepoint [9] 0 0
Up to 27 months
Secondary outcome [10] 0 0
Titers of ADA to GSK4428859A
Timepoint [10] 0 0
Up to 27 months
Secondary outcome [11] 0 0
Serum concentrations of GSK4381562
Timepoint [11] 0 0
Up to 4 months
Secondary outcome [12] 0 0
Serum concentrations of dostarlimab
Timepoint [12] 0 0
Up to 4 months
Secondary outcome [13] 0 0
Serum Concentrations of GSK4428859A
Timepoint [13] 0 0
Up to 4 months
Secondary outcome [14] 0 0
Maximum observed plasma concentration (Cmax) of GSK4381562 monotherapy
Timepoint [14] 0 0
Up to 27 months
Secondary outcome [15] 0 0
Cmax of GSK4381562 in combination with dostarlimab
Timepoint [15] 0 0
Up to 27 months
Secondary outcome [16] 0 0
Cmax of GSK4381562 in combination with GSK4428859A
Timepoint [16] 0 0
Up to 27 months
Secondary outcome [17] 0 0
Cmax following administration of dostarlimab in combination with GSK4428859A
Timepoint [17] 0 0
Up to 27 months
Secondary outcome [18] 0 0
Minimum observed plasma concentration (Cmin) of GSK4381562 monotherapy
Timepoint [18] 0 0
Up to 27 months
Secondary outcome [19] 0 0
Cmin of GSK4381562 in combination with dostarlimab
Timepoint [19] 0 0
Up to 27 months
Secondary outcome [20] 0 0
Cmin of GSK4381562 in combination with GSK4428859A
Timepoint [20] 0 0
Up to 27 months
Secondary outcome [21] 0 0
Cmin following administration of dostarlimab in combination with GSK4428859A
Timepoint [21] 0 0
Up to 27 months
Secondary outcome [22] 0 0
Area under the plasma concentration curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK4381562
Timepoint [22] 0 0
Up to 27 months
Secondary outcome [23] 0 0
AUC(0-t) of GSK4381562 in combination with dostarlimab
Timepoint [23] 0 0
Up to 27 months
Secondary outcome [24] 0 0
AUC(0-t) of GSK4381562 in combination with GSK4428859A
Timepoint [24] 0 0
Up to 27 months
Secondary outcome [25] 0 0
AUC(0-t) following administration of dostarlimab in combination with GSK4428859A
Timepoint [25] 0 0
Up to 27 months
Secondary outcome [26] 0 0
AUC from time zero to infinity (AUC[0-infinity]) of single dosing of GSK4381562
Timepoint [26] 0 0
Up to 27 months
Secondary outcome [27] 0 0
AUC(0-infinity) of single dosing of GSK4381562 in combination with dostarlimab
Timepoint [27] 0 0
Up to 27 months
Secondary outcome [28] 0 0
AUC(0-infinity) of single dosing of GSK4381562 in combination with GSK4428859A
Timepoint [28] 0 0
Up to 27 months
Secondary outcome [29] 0 0
AUC(0-infinity) following administration of dostarlimab in combination with GSK4428859A
Timepoint [29] 0 0
Up to 27 months

Eligibility
Key inclusion criteria
Inclusion criteria:

- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least 1 of the following conditions applies:

- Is not a woman of childbearing potential (WOCBP) or

- Is a WOCBP and using a contraceptive method that is highly effective with a
failure rate of less than (<)1 percent ([%] per year), during the intervention
period and for specified time after end of study treatment.

- A WOCBP must have a negative highly sensitive pregnancy test within 24-48 hours
before the first dose of study intervention.

- Histological or cytological documentation of loco-regionally recurrent solid tumors
where curative treatment options have been exhausted, or metastatic solid tumors;
types as follows:

- head and neck squamous cell carcinoma (HNSCC)

- non-small-cell lung cancer (NSCLC)

- breast cancer (BC)

- clear cell renal cell cancer (ccRCC)

- gastric cancer (GC)

- colorectal cancer (CRC)

- endometrial cancer (EC)

- ovarian epithelial cancer (OEC)

- 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.

•Measurable disease per RECIST 1.1.

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

- Life expectancy of at least 12 weeks.

- Adequate organ function, as defined in the protocol.

- For participants enrolled in a PK/PD cohort, participant agrees to a fresh tumor
biopsy during Screening and at approximately 6-weeks after treatment initiation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior treatment with the following therapies (specified time periods are from last
dose of prior treatment to first dose of GSK4381562):

- Any therapy directed against Polio virus receptor (PVR)-related immunoglobulin
domain-containing (PVRIG) (COM701 or other anti-PVRIG monoclonal antibody [mAb])
or other cluster of differentiation (CD)226 axis receptor (T-cell immunoglobulin
and immunoreceptor tyrosine-based inhibition motif domain [TIGIT] or CD96) at any
time.

- Other prior immunotherapy, chemotherapy, targeted therapy, biological therapy or
radiation therapy within specified periods as defined in the protocol.

- Investigational therapy: if the participant has participated in a clinical study
and has received an investigational product within 4 weeks or 5 half-lives of the
investigational product (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

- History of myocarditis of any grade during a previous treatment with
immunotherapy

- Toxicity related to prior treatment that has not resolved to less than or equal
to (<=)Grade 1. Non clinically relevant Grade 2 toxicities, not constituting a
safety risk by investigator judgment are allowed.

- Participant has a known additional malignancy that progressed or required active
treatment within the last 2 years.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/03/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
14/10/2026
Actual
Sample size
Target
162
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Oklahoma
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Utah
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
China
State/province [8] 0 0
Shnghai
Country [9] 0 0
France
State/province [9] 0 0
Dijon
Country [10] 0 0
France
State/province [10] 0 0
Lille
Country [11] 0 0
Japan
State/province [11] 0 0
Chiba
Country [12] 0 0
Japan
State/province [12] 0 0
Tokyo
Country [13] 0 0
Korea, Republic of
State/province [13] 0 0
Seoul
Country [14] 0 0
Spain
State/province [14] 0 0
Barcelona
Country [15] 0 0
Spain
State/province [15] 0 0
Madrid
Country [16] 0 0
Spain
State/province [16] 0 0
Málaga
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Manchester
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first time in-human (FTIH) study designed to investigate the safety, tolerability,
pharmacokinetics (PK), and immunogenicity of GSK4381562 in participants with select
loco-regionally recurrent solid tumors or metastatic solid tumors where curative or standard
treatment options have been exhausted.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05277051
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
US GSK Clinical Trials Call Center
Address 0 0
Country 0 0
Phone 0 0
877-379-3718
Fax 0 0
Email 0 0
GSKClinicalSupportHD@gsk.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05277051