COBOLIMAB for Relapsed/Refractory tumours | Melanoma | Hodgkin lymphoma | Glioma | Osteosarcoma | Hepatic cancer | Rhabdomyosarcoma

Inclusion criteria

• {"criterion_text":"- Participants must meet the following age criteria at the time of signing the ICF: • Part 1: Cohort 1a: 12 years to <18 years; Cohort 1b: 6 years to <12 years; Cohort 1c: 2 to <6 years; Cohort 1d: 0 to <2 years. • Part 2: Cohort A: 6 to <21 years; Cohort B: 6 to <21 years; Cohort C: Age to be decided."}
• {"criterion_text":"- Type of participants and 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: Melanoma; Hodgkin Lymphoma; High and Low Grade Glioma: including GBM, DIPG, and ependymoma; Osteosarcoma; Hepatic tumors (including Hepatoblastoma, HCC, and Fibrolamellar carcinoma); Rhabdomyosarcoma. • Part 2: Cohort A: Melanoma patients who have not received prior systemic therapy: − Participants with BRAF mutations who are eligible for a BRAF-targeted therapy are eligible if they qualify for immunotherapy. − Participants with locally treated and controlled metastatic CNS lesions without leptomeningeal spread are eligible. Cohort B: Hodgkin lymphoma - Relapsed/refractory Hodgkin lymphoma that has failed at least 2 prior lines of systemic therapy). Cohort C: Indication/s to be decided based on Part 1 results."}
• {"criterion_text":"- Participant has measurable disease, that is, presenting with at least 1 measurable lesion as determined by the local site Investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if disease progression has been demonstrated in such lesions and if there are other target lesions. If there is only 1 target lesion that was previously irradiated, the participant is not eligible. Eligible HL participants must have at least one FDG-avid lesion, preferably with higher intensity than normal liver."}
• {"criterion_text":"- Participants must have performance status ≥60% on the Karnofsky scale for participants >16 years of age and ≥60% on the Lansky scale for participants ≤16 years of age."}
• {"criterion_text":"- Adequate organ function as demonstrated by a complete blood count at screening obtained without transfusion (platelets or RBC) or receipt of CSF, G-CSF, GMCSF or rEPO within 2 weeks prior to screening labs, with the following results: • ANC ≥1,000/μL; • platelets ≥75,000/μL; • hemoglobin ≥9 g/dL or ≥5.6 mmol/L; • glomerular filtration rate ≥50 mL/min; • AST <2.5 × ULN; • ALT <2.5 × ULN; • bilirubin ≤1.5 × ULN; • international normalized ratio or PT ≤1.5×ULN unless the participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants; • activated PTT ≤1.5×ULN unless the participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants."}
• {"criterion_text":"- 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 as described below: Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), during the study intervention period and for at least 150 days after the last dose of study intervention. A WOCBP must a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required."}
• {"criterion_text":"- The Investigator, or a person designated by the Investigator, will obtain written informed consent/assent from each study participant or the participant’s legally acceptable representative, parent(s), or legal guardian and the participant’s assent, when applicable, before any study specific activity is performed."}

Exclusion criteria

• {"criterion_text":"- Participant has uncontrolled CNS involvement by any tumor pathology (this would include leptomeningeal disease, and/or any new or progressive symptoms)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Has any active renal condition (e.g., infection, requirement for dialysis, or any other significant renal condition ( that could affect the participant’s safety)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participant 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"}
• {"criterion_text":"- Participant 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. Note: Low dose prednisone (up to 5 mg daily) or dexamethasone (up to 0.8 mg daily), or equivalent, as needed to manage certain chronic medical conditions, is allowed."}
• {"criterion_text":"- Participant has received any live attenuated vaccine within 30 days of enrollment."}
• {"criterion_text":"- Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live."}
• {"criterion_text":"- Participant has not met the following waiting/washout periods for external beam radiation therapy (XRT)/external beam irradiation including protons: Fourteen days after local palliative radiation therapy; ≥150 days after total body irradiation, craniospinal XRT or if radiation to ≥50% of the pelvis; ≥42 days if other substantial bone marrow radiation."}
• {"criterion_text":"- Participant has a heart rate-corrected QT interval according to QTcF prolongation at screening >470 msec or >480 msec for participants with bundle branch block."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Prior Bone Marrow Transplant <60 days of screening."}
• {"criterion_text":"- Participant has experienced Grade 3 or higher hypersensitivity to prior monoclonal antibody therapy."}
• {"criterion_text":"- Participant 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."}
• {"criterion_text":"- Ongoing drug or alcohol abuse."}
• {"criterion_text":"- Participant has a documented presence of Hepatitis B surface antigen (HbsAg) at Screening or within 3 months prior to first dose of study intervention. Participants with a negative HbsAg and positive hepatitis B core antibody (HbcAb) result are eligible only if HBV DNA is negative."}
• {"criterion_text":"- Participant has a positive HCV antibody test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled, only if a confirmatory HCV RNA test is negative"}
• {"criterion_text":"- Participant has a positive HCV RNA test result at Screening or within 3 months prior to first dose of study intervention. NOTE: The HCV RNA test is optional and participants with negative HCV antibody test are not required to undergo HCV RNA testing as well."}
• {"criterion_text":"- Participant has a known history of HIV or has a HIV-positive test result at Screening."}
• {"criterion_text":"- Participant is pregnant or breastfeeding."}
• {"criterion_text":"- Participant has clinically significant cardiovascular disease (e.g., significant cardiac conduction abnormalities, uncontrolled hypertension, cardiac arrhythmia, Grade 2 or greater congestive heart failure according to New York Heart Association if a young adult or adolescent or the modified Ross Heart Failure Classification in infants and children, serious cardiac arrhythmia requiring medication, and history of cerebrovascular accident) within 6 months of enrolment."}
• {"criterion_text":"- Participant is unable to adhere to the protocol-defined Schedule of Activities, including requirements for the Follow-up Period of the study."}
• {"criterion_text":"- Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study."}
• {"criterion_text":"- Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal)."}
• {"criterion_text":"- Participant has a history of other malignancies prior to study entry, except for: Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and with no evidence of disease recurrence for 2 years since the initiation of that therapy."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Participant who have a history of immunodeficiency disease, including other acquired or congenital immunodeficiency diseases, or organ transplantation."}
• {"criterion_text":"- Participants who have received plasma exchange within 7 days before the first dose of study intervention."}

Primary endpoints

• {"endpoint_text":"- Part 1: • Incidence of DLTs. • Incidence of TEAEs, SAEs, imAEs and AEs leading discontinuation occurring during the study. • IMP serum concentrations up to Cycle 6. • RP2D.","definition_or_measurement_approach":"DLTs, TEAEs, SAEs, immune-related AEs and AEs leading to discontinuation: incidence measured during the study (safety reporting). IMP serum concentrations: measured up to Cycle 6 using serum assays. RP2D: determined based on safety, tolerability and PK in Part 1."}
• {"endpoint_text":"- Part 2: • Confirmed ORR. • The incidence of TEAEs, SAEs, imAEs, TEAEs leading to death, and AEs leading to discontinuation occurring while participants are on treatment or up to 90 days after the last dose of study treatment. • Change in safety assessments (laboratory parameters, vital signs, cardiac parameters).","definition_or_measurement_approach":"Confirmed ORR: objective tumour responses confirmed per protocol-defined radiologic/response criteria. Safety endpoints: incidence measured while on treatment and up to 90 days after last dose. Changes in laboratory, vital signs and cardiac parameters measured per schedule of assessments."}

Secondary endpoints

• {"endpoint_text":"- Part 1: Receptor occupancy measured in whole blood as normalized free-to-total TIM-3 receptor ratio.","definition_or_measurement_approach":"Receptor occupancy assessed in whole blood by measuring free-to-total TIM-3 ratio (normalized) as pharmacodynamic marker."}
• {"endpoint_text":"- Part 1: • Confirmed ORR, • PFS, • DOR, • OS.","definition_or_measurement_approach":"Efficacy measures (ORR, progression-free survival, duration of response, overall survival) assessed per protocol-defined criteria and follow-up schedule."}
• {"endpoint_text":"- Part 1: Incidence and titers of ADAs against cobolimab and dostarlimab.","definition_or_measurement_approach":"Immunogenicity assessed by measuring anti-drug antibodies (incidence and titers) against cobolimab and dostarlimab."}
• {"endpoint_text":"- Part 2: • PFS, • DOR, • OS.","definition_or_measurement_approach":"Progression-free survival, duration of response and overall survival measured per protocol-defined response and follow-up assessments."}
• {"endpoint_text":"- Part 2: Cobolimab and dostarlimab serum concentrations.","definition_or_measurement_approach":"Serum concentrations of cobolimab and dostarlimab measured per PK sampling plan."}
• {"endpoint_text":"- Part 2: Receptor occupancy measured in whole blood as normalized free-to-total TIM-3 receptor ratio.","definition_or_measurement_approach":"Pharmacodynamic receptor occupancy assessed via normalized free-to-total TIM-3 receptor ratio in whole blood."}
• {"endpoint_text":"- Part 2: Incidence and titers of ADAs against cobolimab and dostarlimab.","definition_or_measurement_approach":"Immunogenicity assessed by ADA incidence and titers against cobolimab and dostarlimab."}

Spain

Earliest CTIS Part Ii Submission Date

05-09-2024

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

461

Number Of Sites

5

Number Of Participants

9

France

Earliest CTIS Part Ii Submission Date

07-10-2024

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

233

Number Of Sites

7

Number Of Participants

12

Germany

Earliest CTIS Part Ii Submission Date

30-08-2024

Latest Decision Or Authorization Date

31-01-2025

Processing Time Days

154

Number Of Sites

3

Number Of Participants

9

Denmark

Earliest CTIS Part Ii Submission Date

10-10-2024

Latest Decision Or Authorization Date

05-12-2025

Processing Time Days

421

Number Of Sites

1

Number Of Participants

3

Italy

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

07-02-2025

Processing Time Days

200

Number Of Sites

4

Number Of Participants

9

Czechia

Earliest CTIS Part Ii Submission Date

29-09-2024

Latest Decision Or Authorization Date

05-02-2025

Processing Time Days

129

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Glaxosmithkline Research & Development Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

IQVIA Limited

Responsibilities

codes: 1,12,13,2,5,8

Name

PPD Global Central Labs

Responsibilities

codes: 4

Name

Charles River Laboratories Inc.

Responsibilities

codes: 4

Name

Cellcarta Biosciences Inc.

Responsibilities

codes: 4

Name

Guardant Health Inc.

Responsibilities

codes: 4

Name

Medidata Solutions Inc.

Responsibilities

codes: 7

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"1,12,13,2,5,8","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}