High Grade GliomaPhase 2NCT07644312
Study of Relatlimab and Nivolumab (Opdualag) in Replication Repair Deficient HGG and DIPG
A Phase 2 study testing Opdualag in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital.
Trial summary
The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG. Read more about this study
- Who is it for?
- Ages 12 to 39 years
- Conditions the study is for
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, WHO Grade 3 Glioma
- What is being tested?
- Opdualag
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- No sites listed yet
- Study dates
- 1 Mar 2027to 1 Mar 2038
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 12 to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR.
- Within the United States, patients must weight ≥ 40 kg at the time of enrollment. For all other countries, patients must weight ≥ 30 kg at the time of enrollment.
- Diagnosis:
- Patients with newly-diagnosed HGG, including DIPG, are eligible. All patients mut have histologic confirmation from diagnostic biopsy or resection. The diagnosis of HGG, including DIPG must have been confirmed through TarGeT-SCR.
- All HGGs must be WHO Grade 3 or 4. Note: WHO Grade 2 gliomas with pontine epicenter and diffuse involvement of at least 2/3 of the pons are eligible.
- Disease Status:
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- Patients must be newly diagnosed.
- Measurable disease is not required.
- Patients with primary spinal tumors are eligible.
- Patients should have no evidence of herniation or impending herniation, and no mass effect leading to severe midline shift.
- Patients with prior malignancy are eligible.
- Metastatic disease is excluded.
- Disseminated or multifocal disease: discussion with Study Chairs is required. Patients with multifocal disease who received upfront CSI are not eligible.
- Demonstration of DNA replication repair deficiency (RRD) by fulfilling at least 2 of the following criteria:
- Tumor mutational burden greater than or equal to 5 mutations/megabase (Intermediate and high TMB)
- Genetic diagnosis of germline Constitutional Mismatch Repair Deficiency (CMMRD), Lynch Syndrome, or Polymerase-Proofreading Deficiency (PPD)
- Validated functional genomic assay (e.g. LOGIC) confirming mismatch repair (MMR) deficiency
- Immunohistochemistry (IHC) demonstrating loss of protein expression of any of the 4 MMR genes
- Performance Level: Karnofsky ≥ 50 for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age
- Prior Therapy for HGG:
- Surgery, RT, and/or dexamethasone are permissible. Temozolomide administration is highly discouraged with concurrent RT, but permissible. Anti-VEGF treatment used for vasogenic edema or steroid weaning is permitted. No other prior anticancer therapy for HGG will be allowed. Anti-VEGF use is well-established to not impact outcomes in HGG and is not considered as oncologic treatment but rather as a supportive measure to minimize steroid use in this setting. Discussion with Study Chairs is highly recommended.
- RT requirements: Patients must have received photon or proton focal RT and administered at a standard dose, including:
- 54 Gy in 30 fractions for DIPG
- 54-59.4 Gy in 30-33 fractions for other HGG
- 45-54 Gy for primary spinal cord HGG Note: Variances in RT dose within 10% of standard doses listed above are acceptable.
- Timing between diagnosis and start of RT: Patients must have started RT < 42 calendar days from initial diagnosis.
- Timing post-RT: The earliest patent can begin protocl treatment is 28 days post-completion of RT. It is recommended treatment should begin within 25 days, however patients must start treatment on TarGeT-F no later than 8 weeks post-completion of RT.
- Organ Function Requirements:
- ANC ≥ 1000/mm3
- Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
- Hemoglobin > 8g/dL (may be transfused)
- Creatinine clearance or radioisotope GFR≥ 70 mL/min/1.73 m2 OR serum creatinine based on age/gender as follows:
- 10 to < 13 years: 1.2 mg/dL for males and females 13 to < 16 years: 1.5 mg/dL for males and 1.4 mg/dL for females
- 16 years: 1.7 mg/dL for males and 1.4 mg/dL for females
- AST/ALT < 3 times the ULN. For the purpose of this study, the ULN for ALT and AST is 45 U/L.
- Ejection fraction greater than or equal to 50% as measured by echocardiogram or multiple-gated acquisition
- QTc ≤ 480 msec (by Bazett formula)
- Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
- TSH within institutional guidelines for normal range.
Who cannot join
- Pregnant or breastfeeding patients are excluded.
- Patients with uncontrolled infection.
- Patients with bone marrow failure syndrome.
- Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- Inflammatory bowel disease
- Moderate to severe pulmonary conditions defined by need for medical intervention and/or limiting activities of daily living or shortness of breath with limited exertion.
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- Personal history of pneumonitis.
- Cardiac conditions.
- Patients with a history of severe or life-threatening adverse dermatologic reactions such as SJS or toxic epidermal necrolysis, or other severe reactions that have been associated with prior immune checkpoint inhibitor therapy.
- Active tuberculosis
- Active autoimmune disease requiring systemic treatment in the past 2 years
- Chronic HBV infections with active disease
- Personal known history of HPC who have not completed curative antiviral treatment
- Personal known history of HIV
- Receipt of any organ transplantation
- Treated with other malignancy within 1 year prior to enrollment with the exception of the following: curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, and in situ cervical cancer.
- Receipt of a live or live-attenuated vaccine within 4 weeks prior to enrollment
- Previous treatment with relatlimab
- Patients with ongoing or clinically significant illness, medical or psychiatric conditions that, in the investigator's opinion, could affect the safety of the participant, or could impair assessment of the study's results are not eligible.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Feasibility and Phase 2a Study of Relatlimab and Nivolumab (Opdualag™) in Adolescent and Young Adult Patients Newly Diagnosed With Replication Repair Deficient High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG)
The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG.
Read the detailed description
This is a multicenter, international study of post-radiotherapy (RT) fixed dose combination of nivolumab and relatlimab (Opdualag) to treat adolescent and young adult patients newly diagnosed with replication repair deficient (RRD) HGG and DIPG. The objectives of the study are to further evaluate feasibility and tolerability of Opdualag after RT, and to further characterize the safety and toxicity of Opdualag for patients with RRD HGG. We will also assess the progression free survival and overall survival distribution in patients.
Protocol maintenance therapy of Opdualag must begin no later than 56 days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT. Each cycle will be 28 days in duration and treatment can continue up to a total of 26 cycles. Opdualag will be given intravenously once every 4 weeks.
- Conditions
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, WHO Grade 3 Glioma, WHO Grade 4 Glioma, Replication Repair Deficient
- Being tested
- Opdualag
- Medical subject headings
- Glioma, Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OpdualagDrug
Fixed dose combination of relatlimab and nivolumab (Opdualag)
| Study group | Role | What they receive |
|---|---|---|
| Opdualag Maintenance Therapy | Experimental | Post-RT Opdualag Maintenance Therapy Receives: Drug: Opdualag |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events, Immune Related Adverse Events, and Dose Modifying Toxicities as assessed by CTCAE v6
Assess the feasibility of fixed dose combination of nivolumab and relatlimab as adjuvant therapy following radiation therapy in patients with newly diagnosed replication repair deficiency HGG. Adverse event data will be summarized in tables which will incorporate grade, attribution, and dose delays.
Measured: 4 years
Number of participants that complete the first 3 cycles of maintenance therapy without experiencing dose modifying toxicities
Assess the tolerability of fixed dose combination of nivolumab and relatlimab (Opdualag) as adjuvant therapy following radiation therapy in patients with newly diagnosed replication repair deficient HGG by quantifying the number of participants that complete at least the first 3 cycles of maintenance therapy without experiencing dose modifying toxicities that require permanent discontinuation of Opdualag therapy.
Measured: 4 years
Secondary outcomes (4)
Progression Free Survival in HGG
Estimate PFS distribution for patients with newly diagnosed RRD-HGG who received Opdualag following RT compared to molecularly stratified and matched historical controls
Measured: Day 1 of treatment until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up to 5 years
Overall Survival in HGG
Estimate overall survival distribution for patients with newly diagnosed RRD-HGG who receive Opdualag following RT compared to molecularly stratified and matched historical controls.
Measured: Day 1 of treatment until date of death due to any cause or date of last follow-up, assessed up to 5 years
Correlations between genomic tumor alterations with radiographic response
Explore longitudinal associations of genomic, transcriptomic, epigenetic, and/or immunologic alterations of tumor at diagnosis, recurrence, or autopsy with radiographic response and advanced neuro-imaging measures. Incidence of significant genomic/transcriptomic/epigenetic and/or immunologic alterations found by sequencing and proteomics will be correlated with percent of patients that achieve radiographic responses using RAPNO guidelines.
Measured: Diagnosis until date of death due to any cause or date of last follow-up, assessed up to 5 years
Evaluate health-related quality of life outcomes using PROMIS questionnaire
Using PROMIS questionnaire, evaluate health-related quality of life outcomes of patients newly diagnosed with RRD-HGG from diagnosis through the end of treatment.
Measured: From diagnosis through the end of treatment with Opdualag, usually 2 years per patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start1 Mar 2027 (estimated)
- Primary completion1 Mar 2033 (estimated)
- Study completion1 Mar 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade GliomaStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Fixed dose combination of relatlimab and nivolumab (Opdualag)
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Hospital for Sick Children
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07644312
- Sponsor's protocol ID
- CONNECT TarGeT-F
- Status last verified
- May 2026
- First submitted
- 29 May 2026
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility and Phase 2a Study of Relatlimab and Nivolumab (Opdualag™) in Adolescent and Young Adult Patients Newly Diagnosed With Replication Repair Deficient High-Grade Glioma (HGG), Including Diffuse Intrinsic Pontine Glioma (DIPG)
- ClinicalTrials.gov ID
- NCT07644312
- Acronym / sponsor ID
- CONNECT TarGeT-F
- Conditions
- High Grade Glioma, Diffuse Intrinsic Pontine Glioma, WHO Grade 3 Glioma, WHO Grade 4 Glioma, Replication Repair Deficient
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- The Hospital for Sick Children
- Study start
- 1 Mar 2027 (estimated)
- Primary completion
- 1 Mar 2033 (estimated)
- Study completion
- 1 Mar 2038 (estimated)
- First posted
- 12 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to further evaluate feasibility and tolerability of Opdualag for patients with replication repair deficient HGG, including DIPG.
Detailed description
This is a multicenter, international study of post-radiotherapy (RT) fixed dose combination of nivolumab and relatlimab (Opdualag) to treat adolescent and young adult patients newly diagnosed with replication repair deficient (RRD) HGG and DIPG. The objectives of the study are to further evaluate feasibility and tolerability of Opdualag after RT, and to further characterize the safety and toxicity of Opdualag for patients with RRD HGG. We will also assess the progression free survival and overall survival distribution in patients.
Protocol maintenance therapy of Opdualag must begin no later than 56 days post-completion of RT. The earliest patients can begin protocol treatment is 28 calendar days post-completion of RT. Each cycle will be 28 days in duration and treatment can continue up to a total of 26 cycles. Opdualag will be given intravenously once every 4 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Fixed dose combination of relatlimab and nivolumab (Opdualag)
| Arm | Type | Receives |
|---|---|---|
| Opdualag Maintenance Therapy | Experimental | Drug: OpdualagPost-RT Opdualag Maintenance Therapy |
Who may qualify
- Ages
- 12 to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (39 listed)
- Patients must be ≥12 years and ≤39 years of age at the time of enrollment on TarGeT-SCR.
- Within the United States, patients must weight ≥ 40 kg at the time of enrollment. For all other countries, patients must weight ≥ 30 kg at the time of enrollment.
- Patients with newly-diagnosed HGG, including DIPG, are eligible. All patients mut have histologic confirmation from diagnostic biopsy or resection. The diagnosis of HGG, including DIPG must have been confirmed through TarGeT-SCR.
- All HGGs must be WHO Grade 3 or 4. Note: WHO Grade 2 gliomas with pontine epicenter and diffuse involvement of at least 2/3 of the pons are eligible.
- Patients must be newly diagnosed.
Key exclusion criteria (19 listed)
- Pregnant or breastfeeding patients are excluded.
- Patients with uncontrolled infection.
- Patients with bone marrow failure syndrome.
- Participants who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- Inflammatory bowel disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OpdualagFixed dose combination of relatlimab and nivolumab (Opdualag) | Drug | Opdualag Maintenance Therapy |
Primary outcome
Number of Participants with Adverse Events, Immune Related Adverse Events, and Dose Modifying Toxicities as assessed by CTCAE v6
Time frame: 4 years
Assess the feasibility of fixed dose combination of nivolumab and relatlimab as adjuvant therapy following radiation therapy in patients with newly diagnosed replication repair deficiency HGG. Adverse event data will be summarized in tables which will incorporate grade, attribution, and dose delays.
Number of participants that complete the first 3 cycles of maintenance therapy without experiencing dose modifying toxicities
Time frame: 4 years
Assess the tolerability of fixed dose combination of nivolumab and relatlimab (Opdualag) as adjuvant therapy following radiation therapy in patients with newly diagnosed replication repair deficient HGG by quantifying the number of participants that complete at least the first 3 cycles of maintenance therapy without experiencing dose modifying toxicities that require permanent discontinuation of Opdualag therapy.
4 secondary outcomes
Progression Free Survival in HGG
Time frame: Day 1 of treatment until date of Progressive Disease or death due to any cause or date of last follow-up, assessed up to 5 years
Overall Survival in HGG
Time frame: Day 1 of treatment until date of death due to any cause or date of last follow-up, assessed up to 5 years
Correlations between genomic tumor alterations with radiographic response
Time frame: Diagnosis until date of death due to any cause or date of last follow-up, assessed up to 5 years
Evaluate health-related quality of life outcomes using PROMIS questionnaire
Time frame: From diagnosis through the end of treatment with Opdualag, usually 2 years per patient
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Opdualag in people with High Grade Glioma and Diffuse Intrinsic Pontine Glioma, run by Nationwide Children's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 39 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelsey Troyer, PhD (6147223284, kelsey.troyer@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Adverse Events, Immune Related Adverse Events, and Dose Modifying Toxicities as assessed by CTCAE v6 (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.