TIL Therapy + Pembrolizumab for Advanced Brain Cancer Including Gliomas and Meningiomas
This Phase I/II trial investigates whether autologous tumor-infiltrating lymphocytes (TIL) β immune cells extracted from the patient's own brain tumor β combined with pembrolizumab (Keytruda) can produce measurable responses in patients with advanced gliomas, glioblastoma, and meningiomas who have failed standard therapies. The trial is actively recruiting at District One Hospital in Beijing. CancerFax helps eligible international patients navigate the access and preparation process.
About This Clinical Trial
Brain cancers β particularly high-grade gliomas such as glioblastoma multiforme (GBM) β remain among the most difficult cancers to treat. Despite aggressive standard care combining surgery, radiotherapy, and temozolomide chemotherapy, median overall survival for GBM patients typically ranges from 12 to 18 months. Recurrence is nearly universal, and the options at relapse are extremely limited. The blood-brain barrier, the profoundly immunosuppressive tumor microenvironment, and the high degree of intratumoral heterogeneity in brain tumors have made immunotherapy β including checkpoint inhibitors and cell therapies β especially challenging to translate successfully into clinical practice.
NCT06640582 is a Phase I/II study sponsored by Essen Biotech evaluating autologous tumor-infiltrating lymphocyte (TIL) therapy combined with pembrolizumab (Keytruda) in patients with advanced brain cancer, including gliomas (including glioblastoma and other malignant gliomas) and meningiomas. TILs are isolated directly from the patient's resected or biopsied brain tumor tissue, expanded ex vivo, and reinfused following a non-myeloablative lymphodepletion regimen using cyclophosphamide and fludarabine. Interleukin-2 (IL-2 / aldesleukin) is given post-infusion to sustain TIL activity, and pembrolizumab is administered concurrently to block PD-1-mediated immune exhaustion.
The scientific rationale is compelling even given the known challenges. Brain tumors do harbour tumor-infiltrating lymphocytes, and recent research published in Nature Communications (2025) demonstrated that tumor-reactive TILs can be successfully expanded from glioma tissue in approximately 54% of patients β confirming that TIL manufacturing is feasible for this cancer type. Pembrolizumab adds a mechanistic complement: by blocking the PD-1/PD-L1 axis β which GBM tumors heavily exploit to suppress T-cell function β it may prevent the newly infused TILs from being rapidly exhausted by the immunosuppressive brain tumor microenvironment. Early clinical data from related trials (including NCT03347097) has shown that TIL and PD-1-secreting TIL approaches in GBM are generally well tolerated, with preliminary signs of biological activity.
The trial is modeled on the lifileucel (Amtagvi) framework β the first FDA-approved TIL therapy, approved for advanced melanoma β and extends this approach to brain cancers. The primary endpoint is characterization of the adverse event profile at 6 months (safety-first Phase I design). Secondary efficacy endpoints including ORR, DCR, PFS, and DOR are assessed over up to 36 months using RECIST v1.1 criteria.
Glioblastoma has one of the lowest 5-year survival rates of any cancer. This trial tests whether a patient's own tumor-derived T cells, combined with checkpoint blockade, can generate an immune response that standard therapies cannot achieve.
Trial at a Glance
Key details from the ClinicalTrials.gov registry for NCT06640582. Eligibility is determined only by the trial investigators after full medical record review.
Final eligibility is determined only by the trial investigators after reviewing complete medical records.
Treatment Being Studied
TIL (tumor-infiltrating lymphocyte) therapy is a form of personalized adoptive cell therapy. Unlike chemotherapy or targeted drugs, TIL therapy works by harvesting T cells that have already entered the patient's tumor β cells the body has already 'trained' to recognize that particular cancer β growing them in vast numbers in a laboratory, and returning them to the patient in large quantities alongside immune-boosting agents.
In this trial, pembrolizumab (Keytruda) is added to the TIL infusion specifically to address one of the main ways brain tumors resist immune attack: PD-1-mediated T-cell exhaustion. Brain tumor cells produce PD-L1, which binds to the PD-1 receptor on T cells and effectively switches them off. Pembrolizumab blocks this interaction, potentially keeping the infused TILs active for longer within the hostile brain tumor microenvironment.
How the therapy works (in simple terms)
How it is given
Tumor tissue is collected from the patient's brain tumor via surgical resection or stereotactic biopsy. This sample is the source material for the personalized TIL product. Feasibility of TIL expansion depends on the quality and volume of tissue obtained.
Tumor-reactive lymphocytes are isolated from the collected brain tumor tissue and expanded ex vivo in a specialized GMP-grade laboratory. This manufacturing process takes several weeks and produces billions of tumor-reactive T cells from the original sample.
Prior to TIL infusion, patients receive a non-myeloablative conditioning regimen using cyclophosphamide and fludarabine. This temporarily suppresses existing immune cells to 'make space' for the incoming TILs and reduce competitive inhibition of the infused cells.
The expanded autologous TIL product is infused intravenously. As these are the patient's own cells derived from their specific tumor, they carry natural reactivity against that individual's brain cancer antigens without the foreign cell risks of allogeneic therapies.
Interleukin-2 (aldesleukin) is administered post-infusion to support TIL survival, proliferation, and activity. Pembrolizumab is given to block PD-1, preventing the tumor microenvironment from suppressing the newly infused TILs β a critical step in maintaining immune activity in brain tumors.
All participants are monitored closely for the 6-month primary safety endpoint. Tumor response is assessed using RECIST v1.1 criteria on MRI imaging. Follow-up for efficacy endpoints (ORR, DCR, PFS, DOR) and quality of life continues for up to 36 months.
Brain tumors are typically considered 'cold' β with low immune infiltration. But they do contain TILs, and recent research confirms these can be expanded from glioma tissue in a meaningful proportion of patients. The combination with pembrolizumab addresses the suppressive signals that normally silence those T cells once reinfused.
Who This Trial May Be For
These profiles describe the patients this trial is designed for, based on the published eligibility criteria on ClinicalTrials.gov. They are illustrative β only the trial investigators can confirm actual eligibility after reviewing your full records.
Patients must have a confirmed diagnosis of primary, relapsed, or metastatic brain cancer β including gliomas (such as GBM, Grade 3β4 gliomas), meningiomas, or brain metastases from other primaries. The diagnosis must be pathologically established.
This trial is for patients who have exhausted standard therapies β including surgery, radiotherapy, temozolomide, and other approved agents β or for whom no standard treatment remains available. Prior bevacizumab use does not automatically disqualify.
Patients must have a Karnofsky performance score β₯ 60% or ECOG status of 0, 1, or 2. Patients who are not ambulatory or require significant assistance with daily activities are unlikely to tolerate the conditioning chemotherapy and TIL infusion protocol.
A biopsy or surgical resection must be feasible to collect brain tumor tissue from which TILs can be isolated. Patients with accessible tumor lesions, or malignant body fluid containing tumor cells, are eligible. Tumor location and surgical safety are assessed on a case-by-case basis.
Patients who require daily glucocorticoid treatment at prednisone-equivalent doses greater than 15 mg/day are excluded β steroids suppress immune function and would undermine TIL and pembrolizumab activity. Patients weaned to low or no steroids may be considered.
The entire treatment protocol β including tumor tissue collection, lymphodepletion, TIL infusion, IL-2, and initial monitoring β is conducted at District One Hospital, Beijing. International patients must be able to travel to and remain in Beijing for the full treatment and initial recovery phase.
Eligibility Criteria
The following criteria are taken directly from the ClinicalTrials.gov registry (NCT06640582). Only the trial investigators can confirm eligibility after reviewing your complete medical records.
check_circleInclusion Criteria β May Be Eligible
- βAge: 16 years to 90 years
- βHistologically diagnosed as primary, relapsed, or metastatic brain glioma (or other brain cancer per the trial's scope including meningiomas and brain metastases)
- βExpected lifespan of more than 3 months
- βKarnofsky score β₯ 60% or ECOG performance status 0β2
- βFailed standard treatment regimens, or no standard treatment regimens available
- βTumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated
- βAt least 1 evaluable tumor lesion
- βAbsolute white blood cell count β₯ 2.5Γ10βΉ/L (within 7 days prior to enrollment)
- βAbsolute neutrophil count β₯ 1.5Γ10βΉ/L
- βAbsolute lymphocyte count β₯ 0.7Γ10βΉ/L
- βPlatelet count β₯ 100Γ10βΉ
- βHemoglobin β₯ 90 g/L
- βAPTT β€ 1.5Γ ULN (unless on anticoagulant therapy within previous 3 days)
- βINR β€ 1.5Γ ULN (unless on anticoagulant therapy within previous 3 days)
- βSerum creatinine β€ 1.5 mg/dL (or β€ 132.6 ΞΌmol/L), or creatinine clearance β₯ 50 mL/min
- βSerum ALT/AST β€ 3Γ ULN (subjects with liver metastasis β€ 3Γ ULN)
- βTotal bilirubin β€ 1.5Γ ULN
- βNo absolute or relative contraindications to biopsy or surgery
- βPatients with child-bearing potential must use approved highly effective contraception from informed consent through 1 year after lymphodepletion completion
- βAll prior anti-tumor therapies (including radiotherapy, chemotherapy, biologics) must cease β₯ 28 days before TIL collection
- βAbility to understand and sign informed consent
- βWillingness to comply with follow-up schedule and protocol requirements
cancelExclusion Criteria β May Not Be Eligible
- ΓRequires glucocorticoid treatment with daily prednisone > 15 mg (or equivalent), or autoimmune disease requiring immunomodulatory treatment
- ΓFEV1 < 2 L or DLCO (calibrated) < 40%
- ΓNYHA Grade III or IV congestive heart failure or other clinically significant cardiovascular anomalies
- ΓLow blood pressure, uncontrollable symptomatic coronary artery disease, or ejection fraction < 35%
- ΓSevere cardiac rhythm or conduction abnormality (e.g., ventricular arrhythmia requiring clinical intervention, 2ndβ3rd degree AV block)
- ΓHIV infection or anti-HIV antibody positive
- ΓActive HBV or HCV infection (HBsAg positive and/or anti-HCV positive)
- ΓSyphilis infection or Treponema pallidum antibody positive
- ΓSevere physical or mental disease
- ΓSystemic active infection requiring treatment, or positive blood cultures / imaging evidence of infection
- ΓTreatment within 1 month or ongoing treatment with other medicines, biologic therapy, chemotherapy, or radiotherapy
- ΓHistory of allergy to chemical or biological substances resembling cell therapy
- ΓPrior immunotherapy resulting in irAE of Grade > 3
- ΓPrevious anti-tumor treatment adverse events not resolved to CTCAE 5.0 Grade 1 or below (excluding non-safety concerns such as alopecia)
- ΓPregnancy or lactation
- ΓHistory of organ transplantation, allogeneic stem cell transplantation, or renal replacement therapy
- ΓOther severe systemic diseases or other reasons considered inappropriate for participation by the investigators
Criteria here are illustrative. The trial protocol has its own detailed list. CancerFax can help organize records for review, but only the trial center can confirm participation.
Medical Records and Tests Needed for Review
To begin the eligibility review process, CancerFax will need the following documents. Brain cancer cases require specific neurology and neurosurgery documentation alongside standard oncology records.
How the Trial Process May Work
TIL therapy for brain cancer is among the most logistically complex treatments available. It requires a surgical procedure, an extended laboratory manufacturing phase, hospitalization, and close follow-up. Here is a clear overview of what to expect.
Potential Benefits
These are the scientific and practical reasons patients and oncologists consider this trial. Participation does not guarantee any of these outcomes, and individual responses vary significantly.
TILs are derived directly from the patient's own brain tumor, meaning they carry pre-existing reactivity to that individual's specific tumor antigens. This is a fundamentally different approach from systemic chemotherapy or checkpoint inhibitor monotherapy.
The combination of TIL infusion (restoring anti-tumor T-cell volume) with pembrolizumab (blocking PD-1-mediated exhaustion) addresses two simultaneous reasons immune cells fail in the brain tumor microenvironment β quantity and functional suppression.
This trial does not require PD-L1 positivity, IDH mutation, MGMT methylation, or any other molecular biomarker. Patients across a range of glioma subtypes and histologies may be considered β broadening eligibility compared to many targeted therapy trials.
The protocol is modeled on lifileucel (Amtagvi), the FDA-approved TIL therapy for melanoma, adapted for brain cancer by Essen Biotech. The foundational manufacturing and infusion methodology has proven safe and effective in a related cancer type.
The TIL cell product, pembrolizumab, IL-2, and lymphodepletion chemotherapy are typically provided by the sponsor at no direct cost within the trial protocol β which may significantly reduce the financial burden of accessing this experimental approach.
Participants receive comprehensive safety monitoring for 6 months and tumor response assessment for up to 36 months β providing ongoing clinical oversight and scientific data that may inform future treatment decisions for participants and the broader brain cancer patient population.
For patients with recurrent high-grade glioma or other advanced brain tumors, available options at relapse are extremely limited. This trial tests an entirely different therapeutic approach β using the patient's own immune cells β in a disease where standard treatments have historically failed to produce durable results.
Risks and Side Effects
TIL therapy in brain cancer carries a unique and serious risk profile that reflects both the complexity of the treatment protocol and the specific challenges of treating tumors within the central nervous system. All patients receive intensive medical supervision.
Brain biopsy or craniotomy carries risks of bleeding, neurological deficit, seizure, infection, and anesthesia complications. In patients with tumors near eloquent cortex or deep structures, the risk of post-procedure neurological worsening is particularly relevant. The trial team assesses surgical safety on a case-by-case basis.
The conditioning regimen causes temporary but profound immunosuppression with a significant drop in blood counts (neutropenia, lymphopenia, anemia), increased infection risk, nausea, fatigue, and mucositis. In brain cancer patients who may already have reduced bone marrow reserve, these effects require particularly close inpatient monitoring.
IL-2 (aldesleukin) can cause capillary leak syndrome, hypotension, fluid retention, fever, rigors, and cardiovascular stress. In patients with brain tumors who have altered intracranial pressure dynamics or existing cerebral edema, these systemic effects require specialist management and ICU-capable monitoring.
Pembrolizumab (Keytruda) can trigger immune-related adverse events including pneumonitis, colitis, hepatitis, endocrinopathies (hypothyroidism, adrenal insufficiency), and dermatitis. Neurological irAEs β such as immune-mediated encephalitis β are a specific concern in patients with pre-existing CNS pathology. Grade β₯ 3 irAEs may require immunosuppressive therapy or pembrolizumab discontinuation.
The inflammatory response triggered by TIL infusion and IL-2 may worsen cerebral edema around the tumor site, potentially increasing intracranial pressure and causing neurological deterioration. Managing steroids (needed for edema) against their immunosuppressive effects on TIL activity presents a complex clinical challenge.
The period of severe immunosuppression following lymphodepletion and prior to TIL engraftment carries significant bacterial, fungal, and viral infection risk. Brain cancer patients may already be neurologically compromised, making infection recognition and management more complex.
Published research indicates that successful TIL expansion from glioma tissue occurs in approximately 54% of attempts. Patients with IDH1 mutations or high cumulative steroid doses have lower expansion rates. If sufficient TILs cannot be manufactured from the collected tissue, the patient cannot proceed to infusion β representing a significant practical risk for this treatment approach.
Immunotherapy has historically underperformed in GBM in large randomized trials, due to the blood-brain barrier, low tumor mutation burden, and the profoundly immunosuppressive tumor microenvironment. This trial's combination approach addresses some of these barriers, but clinical benefit cannot be predicted or guaranteed.
The multi-phase treatment process β neurosurgery, TIL manufacturing wait, lymphodepletion, infusion, and recovery β spans several months in total. International patients must plan for an extended stay in Beijing with appropriate caregiver support. CancerFax assists with travel, accommodation, and logistical planning.
This protocol involves neurosurgery for tissue collection, lymphodepletion chemotherapy, IL-2, pembrolizumab, and a large TIL infusion β all in patients with advanced brain cancer who may already have neurological vulnerabilities. The risk profile must be discussed in detail with both the trial team and your existing neurosurgeon or oncologist.
Trial Location and Hospital Information
NCT06640582 is conducted at a single site: District One Hospital, Beijing, China. The trial is sponsored by Essen Biotech, a company with an active portfolio of cell therapy clinical trials at this location. The trial contact is Dr. SAMI XI at District One Hospital.
β VERIFY: The registry does not explicitly state whether international patients are eligible. However, Essen Biotech's stated mission includes connecting international patients with overseas treatment access, and Beijing's major oncology centers β including District One Hospital β regularly treat international patients from across Asia, the Middle East, and beyond. CancerFax can contact the trial team directly to determine your eligibility as an international patient and provide practical support for Beijing-based treatment including visa guidance, accommodation near the trial site, interpreter services, and caregiver logistics.
Costs, Trial Coverage, and Patient Expenses
Cost coverage varies between what is considered investigational (typically sponsored) and standard or supportive care (typically patient-funded). The table below reflects a standard Phase I/II sponsored cell therapy coverage model. Confirm all details with the trial team.
In most sponsored Phase I/II trials, the investigational therapy β here including the TIL product, pembrolizumab, IL-2, and lymphodepletion chemotherapy β is provided by the sponsor at no direct charge within the protocol. Travel, accommodation, caregiver costs, and non-protocol care are the patient's responsibility.
Standard Treatment vs Clinical Trial
This comparison is for educational purposes only. It is not a recommendation to choose the trial over standard care. All treatment decisions should be made with your oncologist and neurosurgeon.
How CancerFax Supports You
CancerFax is a global cancer navigation platform. We help patients and families understand complex advanced treatment options and access trials like this one through structured, human-led support β not direct enrollment.
Our medical team reviews your MRI reports, operative notes, pathology (including IDH/MGMT/molecular status), steroid history, and full treatment records to assess whether you meet the published eligibility criteria β including the steroid-dose threshold that is critical for brain cancer patients.
We map your specific clinical situation against the trial's inclusion and exclusion criteria and give you an honest, plain-language assessment of your likely eligibility β including flagging potential barriers like steroid dependence or tumor inaccessibility β before you commit to travelling to Beijing.
CancerFax contacts the investigator team at District One Hospital on your behalf, submits a structured medical summary, and facilitates the initial dialogue with the trial team. We handle language barriers and institutional communication so you can focus on your health.
We provide practical support for international patients planning to travel to Beijing β including medical visa guidance, accommodation options near District One Hospital, interpreter coordination, and arrival logistics. We understand that brain cancer patients often travel with caregivers who need support too.
If you are not eligible for this specific trial, CancerFax can identify other advanced brain cancer trials globally β including other TIL therapy trials (such as NCT05333588 and NCT04943913 for GBM), CAR-T programs for CNS tumors, and novel immunotherapy combinations in China and internationally.
From your first inquiry through treatment coordination, CancerFax provides coordinated, human-led navigation. We do not replace your oncologist or neurosurgeon β we help you access specialist pathways and global trial opportunities they may not have direct connections to.
CancerFax does not guarantee trial enrollment, treatment response, or outcome. Our role is to help patients access accurate information and appropriate pathways.
Questions to Ask Before Considering This Trial
If you speak with the investigators at District One Hospital or discuss this trial with your neuro-oncologist, these questions will help you make an informed decision.
Frequently Asked Questions
Ready to Explore This Trial?
CancerFax helps advanced brain cancer patients and families understand whether this trial may be an appropriate next step β and navigate the access process if it is. Submit your records for a no-obligation medical review. Our navigation team is experienced with complex neuro-oncology cases and international patient logistics.
The information on this page is for educational and patient-navigation purposes only. It does not replace medical advice, diagnosis, or treatment from a qualified physician. Clinical trial eligibility, enrollment, treatment decisions, and costs are determined only by the trial investigators, hospital, sponsor, and applicable regulations. CancerFax helps patients and families understand options and coordinate case review where appropriate, but does not guarantee trial acceptance, treatment response, or clinical outcome. All clinical decisions must be made in consultation with a qualified, licensed physician with access to the patient's complete medical information.
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