A Study of Cobolimab Plus Dostarlimab in Pediatric and Young Adult Participants With Cancer

Phase 1/2 Dose Determination and Dose Expansion Study of Cobolimab in Combination With Dostarlimab in Pediatric and Young Adult Participants With Newly Diagnosed and Relapsed/Refractory Tumors (POPSTAR)

The goal of this interventional study is to determine the strength of cobolimab and dostarlimab that is most tolerated in children and young adults who have advanced solid tumors. This study also aims: (a) to check if it is safe to use cobolimab and dostarlimab combination in children and young adults, (b) to see how to manage the side effects that may occur, and (c) the effect of this treatment in participants

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Hodgkin Lymphoma; Hepatocellular Carcinoma (HCC); Osteosarcoma; Ependymoma; Rhabdomyosarcoma; Hepatoblastoma; Fibrolamellar Carcinoma; Hepatic Tumors; Glioblastoma Multiforme (GBM); Diffuse Intrinsic Pontine Glioma (DIPG); High and Low Grade Glioma
• Intervention / Treatment: Drug: Cobolimab; Drug: Dostarlimab

• Study Type: Interventional
• Enrollment (Estimated): 83
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia, 61300
    • GSK Investigational Site
  • Phaha 5, Czechia, 15006
    • GSK Investigational Site
• Denmark
  • Copenhagen, Denmark, 2100
    • GSK Investigational Site
• France
  • Bordeaux, France, 33076
    • GSK Investigational Site
  • Lyon, France, 69373
    • GSK Investigational Site
  • Paris, France, 75248
    • GSK Investigational Site
  • Strasbourg, France, 67098
    • GSK Investigational Site
  • Villejuif, France, 94805
    • GSK Investigational Site
• Italy
  • Bologna, Italy, 40138
    • GSK Investigational Site
  • Napoli, Italy, 80123
    • GSK Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28009
    • GSK Investigational Site
  • Madrid, Spain, 28046
    • GSK Investigational Site
  • Valencia, Spain, 46026
    • GSK Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90048
      • GSK Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • GSK Investigational Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • GSK Investigational Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • GSK Investigational Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

• Participants between the age of 0 to not more than 21 years at the time of signing informed consent form (ICF).
• Disease characteristics:

Part 1: Participants with advanced or metastatic solid tumors who have had disease progression after treatment with available therapies that are known to confer clinical benefit and who have limited available treatment options as determined by the investigator. Additionally, exposure to prior immunotherapy or experimental therapies is acceptable:

1. Melanoma
2. Hodgkin Lymphoma
3. High and Low Grade Glioma: including Glioblastoma multiforme (GBM), Diffuse intrinsic pontine glioma (DIPG), and ependymoma.
4. Osteosarcoma
5. Hepatic tumors [including Hepatoblastoma, Hepatocellular carcinoma (HCC), and Fibrolamellar carcinoma]
6. Rhabdomyosarcoma

Part 2:

1. Participants with Melanoma who have not received prior systemic therapy:

   • Participants with BRAF gene, found on chromosome 7 (BRAF) mutations who are eligible for a BRAF-targeted therapy are eligible if they qualify for immunotherapy.
   • Participants with locally treated and controlled metastatic central nervous system (CNS) lesions without leptomeningeal spread are eligible

2. Relapsed/refractory Hodgkin lymphoma (HL) that has failed at least 2 prior lines of systemic therapy)

   • Participants must have performance status >=60 percent (%) on the Karnofsky scale for participants >16 years of age and >=60% on the Lansky scale for participants <=16 years of age.
   • Adequate organ function as demonstrated by a complete blood count at screening obtained without transfusion [platelets or red blood cells (RBC)] or receipt of Colony stimulating factor (CSF), Granulocyte colony stimulating factor (G-CSF), Granulocyte macrophage colony stimulating factor (GMCSF) or rErythropoeitin (rEPO) within 2 weeks prior to screening.
   • Adolescent participants who have entered puberty must consent (be willing) to use of contraceptive measures, or refrain from sexual intercourse, if in line with their usual practice, as well as sperm/egg donation for the duration of treatment

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Medical conditions:

• Participant has uncontrolled CNS involvement by any tumor pathology
• Participant has a heart rate-corrected QT interval according to QT interval (corrected) (Friderecia's formula) (QTcF) prolongation at screening >470 millisecond (msec) or >480 msec for participants with bundle branch block.
• Participant has clinically significant cardiovascular disease
• Participant has chronic respiratory disease
• Participant has known sensitivity to study intervention components or excipients or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
• Participants who have a history of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, or organ transplantation
• Participants who have received plasma exchange within 7 days before the first dose of study intervention.
• Participant has current active pneumonitis or any history of pneumonitis requiring steroids or immunomodulatory treatment within 90 days of planned enrollment or any history of drug-induced pneumonitis.
• Participant has a history of autoimmune disease that has required systemic treatments in the 2 years prior to screening. Participants with prior history of autoimmune disease must be discussed with the medical monitor. Replacement therapy is not considered a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary)
• Participant has ongoing adverse reaction(s) from prior therapy that has (have) not recovered to ≤Grade 1 or to the Baseline status preceding prior therapy, excluding [e.g., alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 neuropathy], or that the investigator, with the agreement of the sponsor, considers to be not clinically relevant for the tolerability of study intervention in the current clinical study.
• Participant has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition (that could affect the participant's safety).
• Participant has any serious and/or unstable medical or psychiatric disorder or other condition(s) (including laboratory assessment abnormalities) that could interfere with the participant's safety, obtainment of informed consent, or compliance to the study procedures.

Prior/ Concomitant therapy:

• Has received treatment with an investigational agent or any other anti-cancer therapy within 30 days, or <5 times the half-life of the most recent therapy prior to signing ICF, whichever is shorter.
• Has received systemic steroid therapy within 3 days prior to the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.
• Has not met the following waiting/washout periods for X-ray therapy (XRT) including external beam radiation therapy/external beam irradiation including protons:
• Participant has had major surgery within 28 days prior to the first dose of study treatment or has not adequately recovered from any AEs (Grade ≤1) and/or complications from any major surgery. Surgical implantation of a port catheter is not exclusionary.
• Prior Bone Marrow Transplant <60 days of screening.
• Participant has experienced Grade 3 or higher hypersensitivity to prior monoclonal antibody therapy.

Prior/Concurrent clinical study experience

• Is currently enrolled or has participated in any other clinical study involving an investigational study or interventional medical research within 21 days or 5 half-lives, whichever is shorter, of an investigational medicinal product before signing ICF Diagnostic assessments
• Has documented presence of Hepatitis B surface antigen (HbsAg) at Screening or within 3 months prior to first dose of study intervention.
• Has a positive Hepatitis C virus (HCV) antibody test result at Screening or within 3 months prior to first dose of study intervention.
• Has a positive HCV Ribonucleic Acid (RNA) test result at Screening or within 3 months prior to first dose of study intervention.
• Has a known history of Human immunodeficiency virus (HIV) or has a HIV-positive test result at Screening.
• Is pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1- Dose determination	Drug: Cobolimab; Cobolimab will be administered; Drug: Dostarlimab; Dostarlimab will be administered
Experimental: Part 2- Dose expansion	Drug: Cobolimab; Cobolimab will be administered; Drug: Dostarlimab; Dostarlimab will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1- Number of participants with Dose Limiting Toxicities (DLTs)		Up to 42 days
Part 1- Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), immune-mediated adverse events (imAEs) and adverse events (AEs) leading to discontinuation occurring during the study		Up to approximately 46 months
Part 1- Serum concentration of Cobolimab		1±0.5 hours (h) post-dose on Cycle 1 Day 1; 168±12 h post-dose Cycle 1Day 8; Pre-dose and 1±0.5 h post-dose on Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1(Each cycle is of 21 days)
Part 1- Serum concentration of Dostarlimab		1±0.5 h post start of cobolimab infusion on Cycle 1 Day 1; Pre-dose on Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1(Each cycle is of 21 days)
Part 1- Recommended Phase 2 Dose (RP2D) of Cobolimab and Dostarlimab combination		Up to approximately 12 months
Part 2- Confirmed Objective Response Rate (ORR)	Confirmed ORR is defined as the proportion of participants who have achieved confirmed complete response (CR) or confirmed partial response (PR), evaluated using disease-specific tumor assessment criteria based on Investigator assessment	Up to approximately 46 months
Part 2- Number of participants with TEAEs, SAEs, imAEs, TEAEs leading to death and AEs leading to discontinuation		Up to approximately 46 months
Part 2-Number of participants with changes in laboratory parameters, vital signs and cardiac parameters		Up to approximately 46 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and 2: Receptor occupancy (RO)	RO will be measured in whole blood and presented as normalized ratio [Fluorescence Minus One (FMO) subtracted values of free T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) to total TIM-3]	Pre-dose Cycle 1 Day 1, 5 h post-start of cobolimab administration Cycle 1 Day 1, anytime Cycle 1 Day 8, pre-dose Cycle 2 Day 1, and pre-dose Cycle 4 Day 1 (Each cycle is of 21 days)
Part 1 and 2: Number of participants with positive results in Anti-drug antibody (ADA) test against Cobolimab		Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 1 and 2: Number of participants with positive results in Anti-drug antibody (ADA) test against Dostarlimab		Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 1 and 2: Titers of ADA to Cobolimab		Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 1 and 2: Titers of ADA to Dostarlimab		Pre-dose on Cycle 1 Day 1; Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1[Each cycle is of 21 days]; 30-Day and 90-Day safety follow up (FUP) Visit
Part 2- Serum concentration of Cobolimab		1±0.5 hours(h) post-dose on Cycle1Day 1;168±12h post-dose Cycle1Day8; Pre-dose & 1±0.5h post-dose on Cycle2Day1; Cycle4Day1 & Cycle6Day1[Each cycle is of 21 days];End of Treatment(EOT; EOT is within 7days of last dose), 30Day safety follow up(FUP) Visit
Part 2- Serum concentration of Dostarlimab		1±0.5 h post start of cobolimab infusion on Cycle 1 Day 1; Pre-dose on Cycle 2 Day 1; Cycle 4 Day 1 and Cycle 6 Day 1 [Each cycle is of 21 days]; End of Treatment (EOT; EOT is within 7 days of last dose), 30-Day safety follow up (FUP) Visit
Part 1- Confirmed ORR	Confirmed ORR is defined as the proportion of participants who have achieved confirmed CR or confirmed PR, evaluated using disease specific tumor assessment criteria based on Investigator assessment	Up to approximately 70 months
Part 1 and 2: Progression Free Survival (PFS)	PFS is defined as the length of time until disease progression, from the date of first dose to the earliest date of assessment of disease progression based on disease-specific tumor assessment criteria by Investigator assessment, or death by any cause, whichever occurs first	Up to approximately 70 months
Part 1 and 2: Duration of response (DOR)	DOR is defined as the time from first documented response (CR/PR) until the time of first documentation of disease progression based on disease-specific tumor assessment criteria by Investigator assessment, or death, whichever occurs first	Up to approximately 70 months
Part 1 and 2: Overall Survival (OS)	OS is defined as the time from the date of first dose to the date of death by any cause	Up to approximately 70 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2025
• Primary Completion (Estimated): October 13, 2026
• Study Completion (Estimated): October 13, 2026

Study Registration Dates

• First Submitted: July 22, 2024
• First Submitted That Met QC Criteria: July 22, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Actual): November 12, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Solid Tumours; Dostarlimab; Cobolimab
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Carcinoma; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Lymphoma; Nervous System Neoplasms; Neuroendocrine Tumors; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Nevi and Melanomas; Skin Neoplasms; Central Nervous System Neoplasms; Neoplasms, Muscle Tissue; Neoplasms, Complex and Mixed; Myosarcoma; Brain Neoplasms; Brain Stem Neoplasms; Infratentorial Neoplasms; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Diffuse Intrinsic Pontine Glioma; Carcinoma, Hepatocellular; Glioblastoma; Melanoma; Hodgkin Disease; Rhabdomyosarcoma; Osteosarcoma; Ependymoma; Hepatoblastoma; Fibrolamellar hepatocellular carcinoma; Antineoplastic Agents; dostarlimab
• Other Study ID Numbers: 219451; 2024-511350-41-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes