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NeoplasmsPhase 1NCT05277051

First-Time-in-Human Study of GSK4381562 in Participants With Advanced Solid Tumors

A Phase 1 study testing Remzistotug, Dostarlimab and Belrestotug in people with Neoplasms, run by GlaxoSmithKline at 26 sites in 9 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This is a first time in-human (FTIH) study designed to investigate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of remzistotug in participants with select loco-regionally recurrent solid tumors or metastatic solid tumors where curative or standard treatment options have been exhausted. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Neoplasms
What is being tested?
Remzistotug, Dostarlimab and Belrestotug
Could I receive a placebo?
No, everyone receives an active treatment
How many people
152 participants
Where
26 sitesin 9 countries
Study dates
22 Mar 2022to 31 Aug 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 19Show fewer
  • 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.

Who cannot join

  • 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.
Show all 11Show fewer
  • 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.

Trial locations and contacts

26 sites in 9 countries.

26 sites in 9 countries

United States7 sites

  • GSK Investigational Site

    Charlotte, North Carolina, 28204

  • GSK Investigational Site

    Dallas, Texas, 75230

  • GSK Investigational Site

    Oklahoma City, Oklahoma, 73104

  • GSK Investigational Site

    Philadelphia, Pennsylvania, 19111

  • GSK Investigational Site

    Salt Lake City, Utah, 84112-5550

  • GSK Investigational Site

    San Antonio, Texas, 78229

  • GSK Investigational Site

    San Francisco, California, 94158

Other trials in United States

China4 sites

  • GSK Investigational Site

    Chengdu, 610041

  • GSK Investigational Site

    Jinan, 250117

  • GSK Investigational Site

    Shanghai, 200126

  • GSK Investigational Site

    Wuhan, 430022

Other trials in China

Spain4 sites

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Madrid, 28040

  • GSK Investigational Site

    Madrid, 28050

  • GSK Investigational Site

    Málaga, 29010

Other trials in Spain

Canada2 sites

  • GSK Investigational Site

    Ottawa, Ontario, K1H 8L6

  • GSK Investigational Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

France2 sites

  • GSK Investigational Site

    Dijon, 21000

  • GSK Investigational Site

    Lille, 59000

Other trials in France

Japan2 sites

  • GSK Investigational Site

    Chiba, 277-8577

  • GSK Investigational Site

    Tokyo, 104-0045

Other trials in Japan

South Korea2 sites

  • GSK Investigational Site

    Seoul, 03080

  • GSK Investigational Site

    Seoul, 03722

Other trials in South Korea

United Kingdom2 sites

  • GSK Investigational Site

    Manchester, M20 4BX

  • GSK Investigational Site

    Sutton, Surrey, SM2 5PT

Other trials in United Kingdom

Australia1 site

  • GSK Investigational Site

    Nedlands, Western Australia, 6009

Other trials in Australia

About this study

Official 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

This is a first time in-human (FTIH) study designed to investigate the safety, tolerability, pharmacokinetics (PK), and immunogenicity of remzistotug in participants with select loco-regionally recurrent solid tumors or metastatic solid tumors where curative or standard treatment options have been exhausted.

Conditions
Neoplasms
Being tested
Remzistotug, Dostarlimab, Belrestotug, Nelistotug, GSK5764227
Keywords
Advanced solid tumors, Metastatic solid tumor, Anticancer agents, Dostarlimab, Remzistotug, GSK4428859A, Belrestotug, Nelistotug, GSK5764227, 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
Medical subject headings
Neoplasms, Neoplasm Metastasis, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Breast Neoplasms, Carcinoma, Renal Cell, Stomach Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RemzistotugDrug

    Remzistotug will be administered.

  • DostarlimabDrug

    Dostarlimab will be administered.

  • BelrestotugDrug

    Belrestotug will be administered.

  • NelistotugDrug

    Nelistotug will be administered.

  • GSK5764227Drug

    GSK5764227 will be administered.

Study groups in NCT05277051
Study groupRoleWhat they receive
Participants Receiving remzistotug Monotherapy (Arm A)ExperimentalNot described
Receives: Drug: Remzistotug
Participants Receiving remzistotug Plus Dostarlimab (Arm B)ExperimentalNot described
Receives: Drug: Remzistotug; Drug: Dostarlimab
Participants Receiving remzistotug Plus Dostarlimab Plus belrestotug (Arm C)ExperimentalNot described
Receives: Drug: Remzistotug; Drug: Dostarlimab; Drug: Belrestotug
Participants Receiving Dostarlimab Plus belrestotug (Arm D)ExperimentalNot described
Receives: Drug: Dostarlimab; Drug: Belrestotug
Participants Receiving dostarlimab Plus belrestotug Plus remzistotug (Arm E)ExperimentalNot described
Receives: Drug: Remzistotug; Drug: Dostarlimab; Drug: Belrestotug
Participants Receiving dostarlimab Plus belrestotug Plus nelistotug (Arm F)ExperimentalNot described
Receives: Drug: Dostarlimab; Drug: Belrestotug; Drug: Nelistotug
China Cohort: Participants receiving dostarlimab (Arm G)ExperimentalNot described
Receives: Drug: Dostarlimab
Participants Receiving GSK5764227 Plus dostarlimab (Arm I)ExperimentalNot described
Receives: Drug: Dostarlimab; Drug: GSK5764227

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 21 days

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

    Measured: Up to 27 months

Secondary outcomes (92)

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

    Measured: Up to 24 months

  2. Number of Participants With Dose Reductions or Delays

    Measured: Up to 24 months

  3. Number of Participants With Withdrawals due to AEs

    Number of participants with adverse events leading to permanent discontinuation of study treatment or withdrawal from study by overall frequency will be assessed.

    Measured: Up to 27 months

  4. Overall Response Rate (ORR)

    Objective response rate will be calculated as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. It is defined as the percentage of participants with a best overall confirmed complete response (CR) or partial response (PR) at any time as per disease-specific criteria.

    Measured: Up to 24 months

  5. Number of Participants With Positive Antidrug Antibodies (ADA) to remzistotug

    Measured: Up to 27 months

  6. Titres of ADA to remzistotug

    Measured: Up to 27 months

  7. Number of Participants With Positive ADA to Dostarlimab

    Measured: Up to 27 months

  8. Titers of ADA to Dostarlimab

    Measured: Up to 27 months

  9. Number of Participants With Positive ADA to belrestotug

    Measured: Up to 27 months

  10. Titers of ADA to belrestotug

    Measured: Up to 27 months

  11. Number of Participants With Positive ADA to nelistotug

    Measured: Up to 27 months

  12. Titers of ADA to nelistotug

    Measured: Up to 27 months

  13. Number of Participants With Positive ADA to GSK5764227

    Measured: Up to 27 months

  14. Titers of ADA to GSK5764227

    Measured: Up to 27 months

  15. Serum Concentrations of remzistotug

    Measured: Up to 4 months

  16. Serum Concentrations of dostarlimab

    Measured: Up to 4 months

  17. Serum Concentrations of belrestotug

    Measured: Up to 4 months

  18. Serum Concentrations of nelistotug

    Measured: Up to 4 months

  19. Serum Concentrations of GSK5764227

    Measured: Up to 4 months

  20. Maximum Observed Plasma Concentration (Cmax) of remzistotug Monotherapy

    Measured: Up to 27 months

  21. Cmax of remzistotug in Combination With Dostarlimab

    Measured: Up to 27 months

  22. Cmax of remzistotug in Combination With dostarlimab and belrestotug

    Measured: Up to 27 months

  23. Cmax following administration of dostarlimab with belrestotug

    Measured: Up to 27 months

  24. Minimum Observed Plasma Concentration (Cmin) of remzistotug Monotherapy

    Measured: Up to 27 months

  25. Cmin of remzistotug in Combination With Dostarlimab

    Measured: Up to 27 months

  26. Cmin of remzistotug in Combination With dostarlimab and belrestotug

    Measured: Up to 27 months

  27. Cmin following administration of dostarlimab with belrestotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  29. AUC(0-t) of remzistotug in Combination With Dostarlimab

    Measured: Up to 27 months

  30. AUC(0-t) of remzistotug in Combination With dostarlimab and belrestotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  33. AUC(0-infinity) of Single Dosing of remzistotug in Combination with Dostarlimab

    Measured: Up to 27 months

  34. AUC(0-infinity) of Single Dosing of remzistotug in Combination With dostarlimab and belrestotug

    Measured: Up to 27 months

  35. AUC(0-infinity) of Single Dosing of remzistotug following administration of dostarlimab with belrestotug

    Measured: Up to 27 months

  36. Cmax of dostarlimab in Combination With remzistotug

    Measured: Up to 27 months

  37. Cmax of dostarlimab in combination with GSK5764227

    Measured: Up to 27 months

  38. Cmax of dostarlimab in combination with remzistotug and belrestotug

    Measured: Up to 27 months

  39. Cmax of dostarlimab in combination with belrestotug

    Measured: Up to 27 months

  40. Cmax of dostarlimab in combination with belrestotug and remzistotug

    Measured: Up to 27 months

  41. Cmax of dostarlimab in combination with belrestotug and nelistotug

    Measured: Up to 27 months

  42. China cohort: Cmax of dostarlimab monotherapy

    Measured: Up to 18 months

  43. Cmin of dostarlimab in Combination With remzistotug

    Measured: Up to 27 months

  44. Cmin of dostarlimab in combination with GSK5764227

    Measured: Up to 18 months

  45. Cmin of dostarlimab in combination with remzistotug and belrestotug

    Measured: Up to 27 months

  46. Cmin of dostarlimab in combination with belrestotug

    Measured: Up to 27 months

  47. Cmin of dostarlimab in combination with belrestotug and remzistotug

    Measured: Up to 27 months

  48. Cmin of dostarlimab in combination with belrestotug and nelistotug

    Measured: Up to 27 months

  49. China cohort: Cmin of dostarlimab monotherapy

    Measured: Up to 18 months

  50. AUC(0-t) of dostarlimab in Combination With remzistotug

    Measured: Up to 27 months

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

    Measured: Up to 18 months

  52. AUC(0-t) of dostarlimab in combination with remzistotug and belrestotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  54. AUC(0-t) of dostarlimab in combination with belrestotug and remzistotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 18 months

  57. AUC(0-infinity) of dostarlimab in Combination With remzistotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  59. AUC(0-infinity) of dostarlimab in combination with remzistotug and belrestotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  61. AUC(0-infinity) of dostarlimab in combination with belrestotug and remzistotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 18 months

  64. T1/2 of dostarlimab in Combination With remzistotug

    Measured: Up to 27 months

  65. T1/2 of dostarlimab in combination with GSK5764227

    Measured: Up to 18 months

  66. China cohort: T1/2 of dostarlimab monotherapy

    Measured: Up to 18 months

  67. Cmax of belrestotug in combination with dostarlimab and belrestotug

    Measured: Up to 27 months

  68. Cmax of belrestotug in combination with dostarlimab

    Measured: Up to 27 months

  69. Cmax of belrestotug in combination with dostarlimab and remzistotug

    Measured: Up to 27 months

  70. Cmax of belrestotug in combination with dostarlimab and nelistotug

    Measured: Up to 27 months

  71. Cmin of belrestotug in combination with dostarlimab and belrestotug

    Measured: Up to 27 months

  72. Cmin of belrestotug in combination with dostarlimab

    Measured: Up to 27 months

  73. Cmin of belrestotug in combination with dostarlimab and remzistotug

    Measured: Up to 27 months

  74. Cmin of belrestotug in combination with dostarlimab and nelistotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  77. AUC (0-t) of belrestotug in combination with dostarlimab and remzistotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  81. AUC (0- infinity) of belrestotug in combination with dostarlimab and remzistotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  83. Cmax of nelistotug in combination with dostarlimab and belrestotug

    Measured: Up to 27 months

  84. Cmin of nelistotug in combination with dostarlimab and belrestotug

    Measured: Up to 27 months

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

    Measured: Up to 27 months

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

    Measured: Up to 27 months

  87. Cmax of GSK5764227 in combination with dostarlimab

    Measured: Up to 18 months

  88. Cmin of GSK5764227 in combination with dostarlimab

    Measured: Up to 18 months

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

    Measured: Up to 18 months

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

    Measured: Up to 18 months

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

    Measured: Up to 18 months

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

    Measured: Up to 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2022
  2. Study start22 Mar 2022
  3. Primary completion30 Jun 2026
  4. Study completion31 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
4 Dose Escalation arms (Arm A: remzistotug alone; Arm B: remzistotug plus dostarlimab; Arm C: remzistotug plus dostarlimab plus belrestotug); Arm I: GSK5764227 plus dostarlimab) and 5 other arms, Arm D (dostarlimab plus belrestotug; Arm E (dostarlimab plus belrestotug plus remzistotug Arm F (dostarlimab plus belrestotug plus nelistotug; Arm G (China cohort: dostarlimab);
Masking
None (open label)
Enrolment
152 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05277051
Sponsor's protocol ID
217228
Other IDs
2023-509414-11-00, 2021-004968-95, 2023-509414-11-00, 2023
Status last verified
Oct 2026
First submitted
3 Mar 2022
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

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