ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial details imported from ClinicalTrials.gov

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

Registration number

NCT05277051

Ethics application status

Date submitted

3/03/2022

Date registered

14/03/2022

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]

2023-509414-11

Secondary ID [2]

217228

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Neoplasms

Condition category

Condition code

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - GSK4381562
Treatment: Drugs - Dostarlimab
Treatment: Drugs - Belrestotug
Treatment: Drugs - Nelistotug
Treatment: Drugs - GSK5764227

Experimental: Participants receiving GSK4381562 monotherapy (Arm A) -

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

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

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

Experimental: Participants receiving dostarlimab plus belrestotug plus GSK4381562 (Arm E) -

Experimental: Participants receiving dostarlimab plus belrestotug plus nelistotug (Arm F) -

Experimental: China Cohort: Participants receiving dostarlimab (Arm G) -

Experimental: China Cohort: Participants receiving dostarlimab plus belrestotug (Arm H) -

Experimental: Participants receiving GSK5764227 plus dostarlimab (Arm I) -

Treatment: Drugs: GSK4381562
GSK4381562 will be administered.

Treatment: Drugs: Dostarlimab
Dostarlimab will be administered.

Treatment: Drugs: Belrestotug
Belrestotug will be administered.

Treatment: Drugs: Nelistotug
Nelistotug will be administered.

Treatment: Drugs: GSK5764227
GSK5764227 will be administered.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Arms A, B, C, I: Number of Participants with dose-limiting toxicities (DLTs)

Timepoint [1]

Up to 21 days

Primary outcome [2]

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Timepoint [2]

Up to 27 months

Secondary outcome [1]

Number of Participants With Clinically Significant Changes in Laboratory Parameters, Electrocardiogram (ECG) and Vital Signs

Timepoint [1]

Up to 24 months

Secondary outcome [2]

Number of Participants With Dose Reductions or Delays

Timepoint [2]

Up to 24 months

Secondary outcome [3]

Number of Participants With Withdrawals due to AEs

Timepoint [3]

Up to 27 months

Secondary outcome [4]

Overall Response Rate (ORR)

Timepoint [4]

Up to 24 months

Secondary outcome [5]

Number of Participants With Positive Antidrug Antibodies (ADA) to GSK4381562

Timepoint [5]

Up to 27 months

Secondary outcome [6]

Titres of ADA to GSK4381562

Timepoint [6]

Up to 27 months

Secondary outcome [7]

Number of Participants With Positive ADA to Dostarlimab

Timepoint [7]

Up to 27 months

Secondary outcome [8]

Titers of ADA to Dostarlimab

Timepoint [8]

Up to 27 months

Secondary outcome [9]

Number of Participants With Positive ADA to belrestotug

Timepoint [9]

Up to 27 months

Secondary outcome [10]

Titers of ADA to belrestotug

Timepoint [10]

Up to 27 months

Secondary outcome [11]

Number of Participants With Positive ADA to nelistotug

Timepoint [11]

Up to 27 months

Secondary outcome [12]

Titers of ADA to nelistotug

Timepoint [12]

Up to 27 months

Secondary outcome [13]

Number of Participants With Positive ADA to GSK5764227

Timepoint [13]

Up to 27 months

Secondary outcome [14]

Titers of ADA to GSK5764227

Timepoint [14]

Up to 27 months

Secondary outcome [15]

Serum Concentrations of GSK4381562

Timepoint [15]

Up to 4 months

Secondary outcome [16]

Serum Concentrations of dostarlimab

Timepoint [16]

Up to 4 months

Secondary outcome [17]

Serum Concentrations of belrestotug

Timepoint [17]

Up to 4 months

Secondary outcome [18]

Serum Concentrations of nelistotug

Timepoint [18]

Up to 4 months

Secondary outcome [19]

Serum Concentrations of GSK5764227

Timepoint [19]

Up to 4 months

Secondary outcome [20]

Maximum Observed Plasma Concentration (Cmax) of GSK4381562 Monotherapy

Timepoint [20]

Up to 27 months

Secondary outcome [21]

Cmax of GSK4381562 in Combination With Dostarlimab

Timepoint [21]

Up to 27 months

Secondary outcome [22]

Cmax of GSK4381562 in Combination With dostarlimab and belrestotug

Timepoint [22]

Up to 27 months

Secondary outcome [23]

Cmax following administration of dostarlimab with belrestotug

Timepoint [23]

Up to 27 months

Secondary outcome [24]

Minimum Observed Plasma Concentration (Cmin) of GSK4381562 Monotherapy

Timepoint [24]

Up to 27 months

Secondary outcome [25]

Cmin of GSK4381562 in Combination With Dostarlimab

Timepoint [25]

Up to 27 months

Secondary outcome [26]

Cmin of GSK4381562 in Combination With dostarlimab and belrestotug

Timepoint [26]

Up to 27 months

Secondary outcome [27]

Cmin following administration of dostarlimab with belrestotug

Timepoint [27]

Up to 27 months

Secondary outcome [28]

Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK4381562

Timepoint [28]

Up to 27 months

Secondary outcome [29]

AUC(0-t) of GSK4381562 in Combination With Dostarlimab

Timepoint [29]

Up to 27 months

Secondary outcome [30]

AUC(0-t) of GSK4381562 in Combination With dostarlimab and belrestotug

Timepoint [30]

Up to 27 months

Secondary outcome [31]

AUC(0-t) following administration of dostarlimab with belrestotug

Timepoint [31]

Up to 27 months

Secondary outcome [32]

AUC From Time Zero to Infinity (AUC[0-infinity]) of Single Dosing of GSK4381562

Timepoint [32]

Up to 27 months

Secondary outcome [33]

AUC(0-infinity) of Single Dosing of GSK4381562 in Combination with Dostarlimab

Timepoint [33]

Up to 27 months

Secondary outcome [34]

AUC(0-infinity) of Single Dosing of GSK4381562 in Combination With dostarlimab and belrestotug

Timepoint [34]

Up to 27 months

Secondary outcome [35]

AUC(0-infinity) following administration of dostarlimab with belrestotug

Timepoint [35]

Up to 27 months

Secondary outcome [36]

Cmax of dostarlimab in Combination With GSK4381562

Timepoint [36]

Up to 27 months

Secondary outcome [37]

Cmax of dostarlimab in combination with GSK5764227

Timepoint [37]

Up to 27 months

Secondary outcome [38]

Cmax of dostarlimab in combination with GSK4381562 followed by belrestotug

Timepoint [38]

Up to 27 months

Secondary outcome [39]

Cmax of dostarlimab in combination with belrestotug

Timepoint [39]

Up to 27 months

Secondary outcome [40]

Cmax of dostarlimab in combination with belrestotug and GSK4381562

Timepoint [40]

Up to 27 months

Secondary outcome [41]

Cmax of dostarlimab in combination with belrestotug and nelistotug

Timepoint [41]

Up to 27 months

Secondary outcome [42]

China cohort: Cmax of dostarlimab monotherapy

Timepoint [42]

Up to 27 months

Secondary outcome [43]

China cohort: Cmax of dostarlimab in combination with belrestotug

Timepoint [43]

Up to 27 months

Secondary outcome [44]

Cmin of dostarlimab in Combination With GSK4381562

Timepoint [44]

Up to 27 months

Secondary outcome [45]

Cmin of dostarlimab in combination with GSK5764227

Timepoint [45]

Up to 27 months

Secondary outcome [46]

Cmin of dostarlimab in combination with GSK4381562 followed by belrestotug

Timepoint [46]

Up to 27 months

Secondary outcome [47]

Cmin of dostarlimab in combination with belrestotug

Timepoint [47]

Up to 27 months

Secondary outcome [48]

Cmin of dostarlimab in combination with belrestotug and GSK4381562

Timepoint [48]

Up to 27 months

Secondary outcome [49]

Cmin of dostarlimab in combination with belrestotug and nelistotug

Timepoint [49]

Up to 27 months

Secondary outcome [50]

China cohort: Cmin of dostarlimab monotherapy

Timepoint [50]

Up to 27 months

Secondary outcome [51]

China cohort: Cmin of dostarlimab in combination with belrestotug

Timepoint [51]

Up to 27 months

Secondary outcome [52]

AUC(0-t) of dostarlimab in Combination With GSK4381562

Timepoint [52]

Up to 27 months

Secondary outcome [53]

AUC(0-t) of dostarlimab in combination with GSK5764227

Timepoint [53]

Up to 27 months

Secondary outcome [54]

AUC(0-t) of dostarlimab in combination with GSK4381562 followed by belrestotug

Timepoint [54]

Up to 27 months

Secondary outcome [55]

AUC(0-t) of dostarlimab in combination with belrestotug

Timepoint [55]

Up to 27 months

Secondary outcome [56]

AUC(0-t) of dostarlimab in combination with belrestotug and GSK4381562

Timepoint [56]

Up to 27 months

Secondary outcome [57]

AUC(0-t) of dostarlimab in combination with belrestotug and nelistotug

Timepoint [57]

Up to 27 months

Secondary outcome [58]

China cohort: AUC(0-t) of dostarlimab monotherapy

Timepoint [58]

Up to 27 months

Secondary outcome [59]

China cohort: AUC(0-t) of dostarlimab in combination with belrestotug

Timepoint [59]

Up to 27 months

Secondary outcome [60]

AUC(0-infinity) of dostarlimab in Combination With GSK4381562

Timepoint [60]

Up to 27 months

Secondary outcome [61]

AUC(0-infinity) of dostarlimab in combination with GSK5764227

Timepoint [61]

Up to 27 months

Secondary outcome [62]

AUC(0-infinity) of dostarlimab in combination with GSK4381562 followed by belrestotug

Timepoint [62]

Up to 27 months

Secondary outcome [63]

AUC(0-infinity) of dostarlimab in combination with belrestotug

Timepoint [63]

Up to 27 months

Secondary outcome [64]

AUC(0-infinity) of dostarlimab in combination with belrestotug and GSK4381562

Timepoint [64]

Up to 27 months

Secondary outcome [65]

AUC(0-infinity) of dostarlimab in combination with belrestotug and nelistotug

Timepoint [65]

Up to 27 months

Secondary outcome [66]

China cohort: AUC(0-infinity) of dostarlimab monotherapy

Timepoint [66]

Up to 27 months

Secondary outcome [67]

China cohort: AUC(0-infinity) of dostarlimab in combination with belrestotug

Timepoint [67]

Up to 27 months

Secondary outcome [68]

Mean terminal half-life (t1/2) of dostarlimab in Combination With GSK4381562

Timepoint [68]

Up to 27 months

Secondary outcome [69]

Mean terminal half-life (t1/2) of dostarlimab in combination with GSK5764227

Timepoint [69]

Up to 27 months

Secondary outcome [70]

China cohort: t1/2 of dostarlimab monotherapy

Timepoint [70]

Up to 27 months

Secondary outcome [71]

China cohort: t1/2 of dostarlimab in combination with belrestotug

Timepoint [71]

Up to 27 months

Secondary outcome [72]

Cmax of belrestotug in combination with dostarlimab followed by GSK4381562

Timepoint [72]

Up to 27 months

Secondary outcome [73]

Cmax of belrestotug in combination with dostarlimab

Timepoint [73]

Up to 27 months

Secondary outcome [74]

Cmax of belrestotug in combination with dostarlimab and GSK4381562

Timepoint [74]

Up to 27 months

Secondary outcome [75]

Cmax of belrestotug in combination with dostarlimab and nelistotug

Timepoint [75]

Up to 27 months

Secondary outcome [76]

China cohort: Cmax of belrestotug in combination with dostarlimab

Timepoint [76]

Up to 27 months

Secondary outcome [77]

Cmin of belrestotug in combination with dostarlimab followed by GSK4381562

Timepoint [77]

Up to 27 months

Secondary outcome [78]

Cmin of belrestotug in combination with dostarlimab

Timepoint [78]

Up to 27 months

Secondary outcome [79]

Cmin of belrestotug in combination with dostarlimab and GSK4381562

Timepoint [79]

Up to 27 months

Secondary outcome [80]

Cmin of belrestotug in combination with dostarlimab and nelistotug

Timepoint [80]

Up to 27 months

Secondary outcome [81]

China cohort: Cmin of belrestotug in combination with dostarlimab

Timepoint [81]

Up to 27 months

Secondary outcome [82]

AUC (0-t) of belrestotug in combination with dostarlimab followed by GSK4381562

Timepoint [82]

Up to 27 months

Secondary outcome [83]

AUC (0-t) of belrestotug in combination with dostarlimab

Timepoint [83]

Up to 27 months

Secondary outcome [84]

AUC (0-t) of belrestotug in combination with dostarlimab and GSK4381562

Timepoint [84]

Up to 27 months

Secondary outcome [85]

AUC (0-t) of belrestotug in combination with dostarlimab and nelistotug

Timepoint [85]

Up to 27 months

Secondary outcome [86]

China cohort: AUC (0-t) of belrestotug in combination with dostarlimab

Timepoint [86]

Up to 27 months

Secondary outcome [87]

AUC (0-infinity) of belrestotug in combination with dostarlimab followed by GSK4381562

Timepoint [87]

Up to 27 months

Secondary outcome [88]

AUC (0- infinity) of belrestotug in combination with dostarlimab

Timepoint [88]

Up to 27 months

Secondary outcome [89]

AUC (0- infinity) of belrestotug in combination with dostarlimab and GSK4381562

Timepoint [89]

Up to 27 months

Secondary outcome [90]

AUC (0- infinity) of belrestotug in combination with dostarlimab and nelistotug

Timepoint [90]

Up to 27 months

Secondary outcome [91]

China cohort: AUC (0- infinity) of belrestotug in combination with dostarlimab

Timepoint [91]

Up to 27 months

Secondary outcome [92]

China cohort: t1/2 of belrestotug in combination with dostarlimab

Timepoint [92]

Up to 27 months

Secondary outcome [93]

Cmax of nelistotug in combination with dostarlimab and belrestotug

Timepoint [93]

Up to 27 months

Secondary outcome [94]

Cmin of nelistotug in combination with dostarlimab and belrestotug

Timepoint [94]

Up to 27 months

Secondary outcome [95]

AUC (0-t) of nelistotug in combination with dostarlimab and belrestotug

Timepoint [95]

Up to 27 months

Secondary outcome [96]

AUC (0-infinity) of nelistotug in combination with dostarlimab and belrestotug

Timepoint [96]

Up to 27 months

Secondary outcome [97]

Cmax of GSK5764227 in combination with dostarlimab

Timepoint [97]

Up to 27 months

Secondary outcome [98]

Cmin of GSK5764227 in combination with dostarlimab

Timepoint [98]

Up to 27 months

Secondary outcome [99]

AUC (0-t) of GSK5764227 conjugated antibody (Ab) in combination with dostarlimab

Timepoint [99]

Up to 27 months

Secondary outcome [100]

AUC (0-t) of GSK5764227 small molecule toxin in combination with dostarlimab

Timepoint [100]

Up to 27 months

Secondary outcome [101]

AUC (0-infinity) of GSK5764227 conjugated Ab in combination with dostarlimab

Timepoint [101]

Up to 27 months

Secondary outcome [102]

AUC (0-infinity) of GSK5764227 small molecule toxin in combination with dostarlimab

Timepoint [102]

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.
* Requirement for Arm I only: Male participants agree to use contraception and for their female partner to use contraception, if applicable.
* 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)
* epithelial ovarian, fallopian tube, and primary peritoneal cancers- 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?

Key exclusion criteria

* Prior treatment with the following therapies (specified time periods are from last dose of prior treatment to first dose of study intervention):

* 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.
* For Arm I only, prior treatment with orlotamab, enoblituzumab, I-Dxd, or other B7-H3 targeted agents.
* 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

12/09/2028

Actual

Sample size

Target

141

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

GSK Investigational Site - Nedlands

Recruitment postcode(s) [1]

6009 - Nedlands

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

North Carolina

Country [3]

United States of America

State/province [3]

Oklahoma

Country [4]

United States of America

State/province [4]

Pennsylvania

Country [5]

United States of America

State/province [5]

Texas

Country [6]

United States of America

State/province [6]

Utah

Country [7]

Canada

State/province [7]

Ontario

Country [8]

China

State/province [8]

Jinan

Country [9]

China

State/province [9]

Shanghai

Country [10]

France

State/province [10]

Dijon Cedex

Country [11]

France

State/province [11]

Lille

Country [12]

Japan

State/province [12]

Chiba

Country [13]

Japan

State/province [13]

Tokyo

Country [14]

Korea, Republic of

State/province [14]

Seoul

Country [15]

Spain

State/province [15]

Barcelona

Country [16]

Spain

State/province [16]

Madrid

Country [17]

Spain

State/province [17]

MAlaga

Country [18]

United Kingdom

State/province [18]

Manchester

Country [19]

United Kingdom

State/province [19]

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/study/NCT05277051

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

GSK Clinical Trials

Address

GlaxoSmithKline

Country

Phone

Fax

Contact person for public queries

Name

US GSK Clinical Trials Call Center

Address

Country

Phone

877-379-3718

Fax

GSKClinicalSupportHD@gsk.com

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Yes

What data in particular will be shared?

IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)

When will data be available (start and end dates)?

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

Available to whom?

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Available for what types of analyses?

How or where can data be obtained?

IPD available at link: http://clinicalstudydatarequest.com

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05277051

Register a trial

Registering a new trial?

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