Epithelial Tumors, MalignantEarly Phase 1NEXTGENTIL-ACTNCT05141474
Assessment of the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
A Early Phase 1 study testing NEXTGEN-TIL, Non-myeloablative Lymphodepletion (NMA-LD) Regimen and Interleukin-2 in people with Epithelial Tumors, Malignant and Malignant Solid Tumor, run by Vall d'Hebron Institute of Oncology at 1 site in Spain.
Trial summary
Background: The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epithelial Tumors, Malignant, Malignant Solid Tumor
- What is being tested?
- NEXTGEN-TIL, Non-myeloablative Lymphodepletion (NMA-LD) Regimen and Interleukin-2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSpain
- Study dates
- 28 Oct 2021to 1 Jan 2027
- Phase
- Early Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically proven metastatic or unresectable solid tumors. The disease must have progressed to at least one standard therapy (including at least one prior line with ICB for the group of patients with tumors where ICB is approved), or the patient is unable/unwilling to receive standard therapy or no standard therapy exists for a particular disease.
- Patients must have at least one adequate lesion (primary tumor or metastasis) for resection or biopsy for TIL generation with minimal morbidity (preferentially using imaging-guided minimally invasive procedures).
- Note: If this lesion was previously irradiated, the lesion must have demonstrated progression prior to resection/biopsy.
- Patient must be at least 18 years old at the tissue procurement visit.
- Patient must understand and voluntarily sign an informed consent document before any study-related assessments/procedures being conducted.
- Patient must be able and willing to comply to the study visit schedule and protocol requirements.
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- Patients must have a clinical performance of Eastern Cooperative Oncology Group 0 or 1.
- Patients are considered medically fit enough by investigator to undergo all study procedures and interventions.
- Patients with documented left ventricular ejection fraction (LVEF) of ≥45%.
- Patients with documented forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) ≥50% tested by a pulmonary function test.
- Patients must be seronegative for HIV antibody (patients who are HIV seropositive may be less responsive and more susceptible to toxicities related to this experimental treatment since they may have a decreased immune competence).
- Patients must be seronegative for active hepatitis B (defined as having a negative hepatitis B surface antigen [HBsAg] test), and seronegative for hepatitis C (HCV) antibody. Patients with a history of hepatitis B virus (HBV) infection and having a negative HBsAg test and a positive antibody to hepatitis B surface antigen (HBsAg) are eligible. Patients with the hepatitis C antibody test positive are eligible only if tested for the presence of antigen by RT-PCR and be HCV RNA negative.
- Life expectancy ≥6 months.
- Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last dose of IL-2.
- The disease must have progressed to the last standard therapy, including at least one prior line with ICB for the group of patients with tumors where ICB is approved, and no subsequent approved therapy is available, or the patients are unable/unwilling to receive standard therapy, or no standard therapy exists for a particular disease.
- Patients must have a remaining measurable disease as defined by RECIST v. 1.1 criteria following tumor resection/biopsy for NEXTGEN-TIL manufacturing.
- Note: Lesions previously irradiated should not be selected as target lesions unless there has been demonstrated progression in those lesions.
- Patients must understand and voluntarily sign an informed consent document before any study-related assessments/procedures being conducted.
- Patients must be able and willing to comply with the study visit schedule and protocol requirements.
- Patients must have a clinical performance of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Patients are considered medically fit enough to undergo all study procedures and interventions and adequate hematological, renal and hepatic functions defined by:
- Haemoglobin ≥9.0 g/dL.
- An absolute neutrophil count ≥1000/mm3 without the support of filgrastim.
- Platelets ≥ 100 x10⁹ /mm3.
- PT and aPTT ≤1.5 x upper limit of normal (ULN, unless receiving therapeutic anticoagulation). Subjects receiving therapeutic anticoagulation (such as low-molecularweight heparin or warfarin) should be on a stable dose.
- AST or ALT ≤3 x ULN. Patients with liver metastases must have AST and ALT ≤5.0 x ULN.
- Total bilirubin <2 mg/dL. Patients with Gilbert's Syndrome must have a total bilirubin ≤3.0 mg/dL.
- Serum creatinine <1.5 mg/dL or measured creatinine clearance ≥50 ml/min calculated using the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female)/72 × (serum creatinine in mg/dL).
- Patients must be seronegative for HIV antibody.
- Patients must be seronegative for active hepatitis B (defined as having a negative hepatitis B surface antigen [HBsAg] test), and seronegative for hepatitis C antibody. Patients with a history of hepatitis B virus (HBV) infection and having a negative HBsAg test and a positive antibody to hepatitis B surface antigen (HBsAg) are eligible. Patients with the hepatitis C antibody test positive are eligible only if tested for the presence of antigen by RT-PCR and be HCV RNA negative.
- Life expectancy ≥3 months.
- Patients who are of childbearing potential (postmenarcheal who has not reached a postmenopausal state and has not undergone surgical sterilization) or have partners of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 6 months after the last dose of IL-2.
- Female participants: a female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Women of non-childbearing potential (WONCBP).
- Women of childbearing potential (WOCBP), who:
- Agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1% per year from screening until 6 months after the infusion of the NEXTGEN-TIL product. Examples of contraceptive methods with a failure rate of <1% per year include bilateral tubal occlusion, male sterilization, and copper intrauterine devices.
- Have a negative pregnancy test (blood) within one week before the first study treatment administration (applicable to premenopausal women and women ≤2 years after the start of menopause (menopause is defined as amenorrhea for <2 years).
- Male Participants: during the treatment period and for at least 2 months after the last dose of study treatment, agreement to:
- Remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom or a contraceptive method that result in a failure rate of <1% per year, with partners who are WOCBP.
- Refrain from donating sperm during the study.
- Inform if his partner gets pregnant during this time.
- Any toxicity related to prior systemic therapy must have recovered to grade 1 or less according to NCI-CTCAE v5.0 at least 4 weeks before treatment enrollment, except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy, and Grade ≤2 peripheral neuropathy.
- Note: Other Grade 2 AEs that are deemed clinically insignificant by treating physician and in consultation with Medical Monitor are permitted.
- Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less.
Who cannot join
- Patients with symptomatic and/or untreated brain metastases. Note: Patients with definitively-treated brain metastases will be considered for enrollment after discussion with Medical Monitor; if, prior to the start of NMA-LD the patient is clinically stable for ≥3 months, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require corticosteroid treatment >10 mg prednisone or equivalent per day.
- Patients with leptomeningeal carcinomatosis.
- Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for > 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.
- Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.
- Patients with active hepatitis B or hepatitis C.
- Patients with active autoimmune disease requiring immunosuppressive treatments.
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- Patients with a history of organ or bone marrow transplantation.
- Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
- Patients requiring regular treatment with steroids at a dose higher than prednisone 10 mg/day (or equivalent).
- Note: use of inhaled, topical steroids and use of systemic physiologic corticosteroid replacement therapy are permitted.
- Patients with current or history within the last 6 months, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, hematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease.
- Patients with a history of coronary revascularization or ischemic symptoms.
- History of idiopathic pulmonary fibrosis or evidence of active pneumonitis (any origin)
- Patients with allergies to any of the compounds included in any of the treatment products.
- Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses.
- Patients who have received any approved anti-cancer cytotoxic, anti-angiogenic and ICB therapy including radiotherapy within 4 weeks before preparative lymphodepleting therapy. Exception: palliative radiotherapy for bone metastasis >2 weeks before preparative lymphodepleting therapy, denosumab, bisphosphonates, androgen deprivation therapy for prostate cancer and hormonal therapy for breast cancer.
- Patients who have received any non-cytotoxic drug and molecular targeted therapy within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).
- Patients who have received any investigational agent within 4 weeks before preparative lymphodepleting therapy (or within five half-lives of the investigational product, whichever is shorter).
- Patients who have received a live, attenuated vaccination within the 4 weeks before lymphodepleting therapy.
- Patients who have undergone major surgery in the previous 3 weeks before lymphodepleting therapy.
- Patients who have previously received any investigational cell or gene therapies.
- Women of childbearing potential who are pregnant or breastfeeding.
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Susana Muñoz contact
Spain1 site, 1 recruiting
- Recruiting
Vall d'Hebron Institute of Oncology
Barcelona
Elena Garralda, MD, 0034 93 489 30 00, egarralda@vhio.net
Elena Garralda, MD
About this study
Official title: A Phase I Study to Assess the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
Background:
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.
Read more
Adoptive cell therapy using tumor-infiltrating lymphocytes product (TIL-ACT) is a well-established combination therapy currently under study in several world reference centers, using an autologous cell product without genetic modifications. This cell product consists of tumor-infiltrating lymphocytes (TIL), which are collected from the patient and expanded in the lab under specific conditions to enhance its antitumoral efficacy before reinfusion in the same patient. However, this cell product alone does not achieve adequate efficacy, and a combination of both previous non-myeloablative lymphodepleting (NMA-LD) chemotherapy and subsequent cytokine therapy (specifically IL-2) is needed to support the expansion of the infused cells.
The investigators hypothesize that TILs enriched for neoantigen recognition are superior to unselected TILs at mediating tumor regression in patients with epithelial tumors and even other solid tumors where immune checkpoint blockade (ICB) is approved and used as part of standard therapy. The investigators propose to manufacture a T-cell product composed of TILs that are selected based on their ability to recognize patient-specific neoantigens and to use these to treat patients with metastatic, refractory, epithelial cancers, as well as ICB-resistant solid tumors. Furthermore, it also proposed to study the tumor and T cells at baseline and after treatment to investigate whether specific phenotypic and functional traits may be associated with clinical outcome.
Primary objective:
To evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or unresectable epithelial tumors and immune checkpoint blockade (ICB) resistant solid tumors.
Secondary objectives:
- To determine the success in producing active specific TILs from our target patients.
- To evaluate the initial clinical activity of the NEXTGEN-TIL products in our target patients.
Read the detailed description
Methods:
This study is a first-in-human, open-label, non-controlled, single-centre, phase I trial to assess the safety and tolerability of NEXTGEN-TIL-ACT. Given the exploratory nature of the study, there is no formal hypothesis testing and no formal sample size calculation was carried out.
A sample size of 10 patients has been selected to provide information about the frequency of treatment-limiting toxicity (TLT).
Study treatment:
The main study therapy is the Tumor-infiltrating Lymphocyte (NEXTGEN-TIL) product, which is preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion.
NEXTGEN-TIL product is a cellular investigational product comprising a live cell suspension of autologous tumor-infiltrating lymphocytes derived from the patient's own tumor.
- Being tested
- NEXTGEN-TIL, Non-myeloablative Lymphodepletion (NMA-LD) Regimen, Interleukin-2
- Keywords
- Immune checkpoint blockade resistant tumors, Tumor-infiltrating Lymphocyte, Adoptive Cell Therapy
- Medical subject headings
- Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NEXTGEN-TILBiological
Also called Tumor-infiltrating Lymphocyte Adoptive Cell Therapy
NEXTGEN-TIL product is a cellular investigational product comprising a live cell suspension of autologous tumor-infiltrating lymphocytes derived from the patient's own tumor.
Each dose contains at least 5 x 10^8 total viable lymphocytes, and a maximum of 1.11x10^11. It will be administered IV on Day 0 (24h after the last dose of Fludarabine).
Non-myeloablative Lymphodepletion (NMA-LD) RegimenDrug
Also called Cyclophosphamide, Fludarabine
Patients will receive a NMA-LD chemotherapy based on Cyclophosphamide 60 mg/kg IV (once daily on Days -5 and -4) and Fludarabine 25 mg/m2 IV (once daily on Days -5 to -1).
Interleukin-2Drug
Also called IL-2, Aldesleukin
Patients will receive sequential doses of 720,000 IU/kg IV IL-2 every 8-24 hours depending on patient tolerance. It will be administered on Days 0 to 2, starting between 3 and 24 hours after the completion of NEXTGEN-TIL infusion.
IL-2 doses may be skipped in case of toxicity. If 2 sequential doses or more than 2 non-sequential doses of IL-2 are skipped due to patient intolerance or the discretion of the investigator, IL-2 administration must be stopped.
| Study group | Role | What they receive |
|---|---|---|
| NEXTGEN-TIL | Experimental | Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years. Receives: Biological: NEXTGEN-TIL; Drug: Non-myeloablative Lymphodepletion (NMA-LD) Regimen; Drug: Interleukin-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events (AE)
Nature and frequency of AE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measured: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first
Incidence of Serious Adverse Events (SAE)
Nature and frequency of SAE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measured: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first
Treatment-limiting Toxicity (TLT)
Toxicities related to treatment administration that, if recurrent at high enough frequency (≥2 patients treated), should trigger review by the Independent Data Safety Monitoring Board (IDSMB), which could lead to recommendations for treatment modifications for subsequent patients.
Measured: From the first dose of study treatment (Day -5) to 30 days after
Incidence of alterations in clinical laboratory test results
Nature and frequency of abnormalities found in clinical laboratory test results
Measured: From baseline through study completion, an average of 2 years
Incidence of alterations in electrocardiogram assessment
Nature and frequency of abnormalities found in electrocardiogram
Measured: From baseline through study completion, an average of 2 years
Incidence of alterations in vital signs measurements
Nature and frequency of abnormalities found in vital signs.
Measured: From baseline through study completion, an average of 2 years
Incidence of physical examination findings
Nature and frequency of abnormalities found in the physical examination.
Measured: From baseline through study completion, an average of 2 years
Assessment of performance status
Patient performance status assessed as per Eastern Cooperative Oncology Group (ECOG) score, where grade 0 is for fully active and capable patient and grade 5 is death.
Measured: From baseline through study completion, an average of 2 years
Secondary outcomes (4)
Neoantigen-selected TIL analysis
Rate of successful neoantigen-selected TIL (NEXTGEN-TIL) generation from biopsied patients and frequency of neoantigen-specific TILs in all TILs produced from biopsied patients included in this trial.
Measured: At baseline
Overall Response Rate (ORR)
ORR per RECIST v1.1 as assessed by investigator, defined as proportion of patients who have a partial or complete response to therapy.
Measured: From baseline through disease progression, assessed up to 36 months after last dose of IL-2
Duration of Response (DOR)
DOR per RECIST v1.1 as assessed by investigator, defined as the time elapsed between the initial response to therapy and subsequent disease progression or relapse.
Measured: From baseline through disease progression, assessed up to 36 months after last dose of IL-2
Progression-Free Survival (PFS)
PFS per RECIST v1.1 as assessed by investigator, defined as the time from the date of treatment administration to the date of first documentation of disease progression or death due to any cause, whichever occurs first. For a patient who has not progressed and is last known to be alive, PFS will be censored at the last response assessment that is stable disease (SD) or better.
Measured: From baseline through disease progression, assessed up to 36 months after last dose of IL-2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2021
- Study start28 Oct 2021
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Epithelial Tumors, MalignantStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- First-in-human, open-label, non-controlled, single-centre, phase I trial. Sequential recruitment: The first six patients will be included for safety assessment. If no more than one treatment-limiting toxicity (TLT) is observed, four additional patients will be included for the final safety population analysis (a total of 10 patients).
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vall d'Hebron Institute of Oncology
- Sponsor type
- University, hospital or other
- Collaborators
- Banc de Sang i Teixits
- Responsible party
- Sponsor
- Investigators
- Elena Garralda, Principal investigator, Vall d'Hebron Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05141474
- Sponsor's protocol ID
- VHIO20001
- Acronym
- NEXTGENTIL-ACT
- Status last verified
- Nov 2024
- First submitted
- 28 Oct 2021
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
- ClinicalTrials.gov ID
- NCT05141474
- Acronym / sponsor ID
- NEXTGENTIL-ACT / VHIO20001
- Keywords
- Immune checkpoint blockade resistant tumors, Tumor-infiltrating Lymphocyte, Adoptive Cell Therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Vall d'Hebron Institute of OncologyUniversity, hospital or other
- Collaborators
- Banc de Sang i Teixits
- Study start
- 28 Oct 2021 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 2 Dec 2021 (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.
Background:
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.
Adoptive cell therapy using tumor-infiltrating lymphocytes product (TIL-ACT) is a well-established combination therapy currently under study in several world reference centers, using an autologous cell product without genetic modifications. This cell product consists of tumor-infiltrating lymphocytes (TIL), which are collected from the patient and expanded in the lab under specific conditions to enhance its antitumoral efficacy before reinfusion in the same patient. However, this cell product alone does not achieve adequate efficacy, and a combination of both previous non-myeloablative lymphodepleting (NMA-LD) chemotherapy and subsequent cytokine therapy (specifically IL-2) is needed to support the expansion of the infused cells.
The investigators hypothesize that TILs enriched for neoantigen recognition are superior to unselected TILs at mediating tumor regression in patients with epithelial tumors and even other solid tumors where immune checkpoint blockade (ICB) is approved and used as part of standard therapy. The investigators propose to manufacture a T-cell product composed of TILs that are selected based on their ability to recognize patient-specific neoantigens and to use these to treat patients with metastatic, refractory, epithelial cancers, as well as ICB-resistant solid tumors. Furthermore, it also proposed to study the tumor and T cells at baseline and after treatment to investigate whether specific phenotypic and functional traits may be associated with clinical outcome.
Primary objective:
To evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or unresectable epithelial tumors and immune checkpoint blockade (ICB) resistant solid tumors.
Secondary objectives:
- To determine the success in producing active specific TILs from our target patients.
- To evaluate the initial clinical activity of the NEXTGEN-TIL products in our target patients.
Detailed description
Methods:
This study is a first-in-human, open-label, non-controlled, single-centre, phase I trial to assess the safety and tolerability of NEXTGEN-TIL-ACT. Given the exploratory nature of the study, there is no formal hypothesis testing and no formal sample size calculation was carried out.
A sample size of 10 patients has been selected to provide information about the frequency of treatment-limiting toxicity (TLT).
Study treatment:
The main study therapy is the Tumor-infiltrating Lymphocyte (NEXTGEN-TIL) product, which is preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion.
NEXTGEN-TIL product is a cellular investigational product comprising a live cell suspension of autologous tumor-infiltrating lymphocytes derived from the patient's own tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- First-in-human, open-label, non-controlled, single-centre, phase I trial. Sequential recruitment: The first six patients will be included for safety assessment. If no more than one treatment-limiting toxicity (TLT) is observed, four additional patients will be included for the final safety population analysis (a total of 10 patients).
| Arm | Type | Receives |
|---|---|---|
| NEXTGEN-TIL | Experimental | Biological: NEXTGEN-TIL, Drug: Non-myeloablative Lymphodepletion (NMA-LD) Regimen, Drug: Interleukin-2Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (44 listed)
- Patients must have histologically or cytologically proven metastatic or unresectable solid tumors. The disease must have progressed to at least one standard therapy (including at least one prior line with ICB for the group of patients with tumors where ICB is approved), or the patient is unable/unwilling to receive standard therapy or no standard therapy exists for a particular disease.
- Patients must have at least one adequate lesion (primary tumor or metastasis) for resection or biopsy for TIL generation with minimal morbidity (preferentially using imaging-guided minimally invasive procedures).
- Note: If this lesion was previously irradiated, the lesion must have demonstrated progression prior to resection/biopsy.
- Patient must be at least 18 years old at the tissue procurement visit.
- Patient must understand and voluntarily sign an informed consent document before any study-related assessments/procedures being conducted.
Key exclusion criteria (23 listed)
- Patients with symptomatic and/or untreated brain metastases. Note: Patients with definitively-treated brain metastases will be considered for enrollment after discussion with Medical Monitor; if, prior to the start of NMA-LD the patient is clinically stable for ≥3 months, there are no new brain lesions via magnetic resonance imaging (MRI) post-treatment, and the patient does not require corticosteroid treatment >10 mg prednisone or equivalent per day.
- Patients with leptomeningeal carcinomatosis.
- Patients with an active concurrent or history within the past 3 years of invasive malignancy, except for non-melanoma skin cancer, cervical and bladder carcinoma in situ, good prognosis ductal carcinoma in situ of the breast, or prostate carcinoma that is in remission under androgen deprivation therapy for > 2 years. Other exceptions may apply and require discussion between the Investigator and the Medical Monitor.
- Patients with an active systemic infection requiring anti-infective treatment within 14 days before preparative lymphodepleting therapy.
- Patients with active hepatitis B or hepatitis C.
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 |
|---|---|---|
| NEXTGEN-TILAlso: Tumor-infiltrating Lymphocyte Adoptive Cell TherapyNEXTGEN-TIL product is a cellular investigational product comprising a live cell suspension of autologous tumor-infiltrating lymphocytes derived from the patient's own tumor. Each dose contains at least 5 x 10^8 total viable lymphocytes, and a maximum of 1.11x10^11. It will be administered IV on Day 0 (24h after the last dose of Fludarabine). | Biological | NEXTGEN-TIL |
| Non-myeloablative Lymphodepletion (NMA-LD) RegimenAlso: Cyclophosphamide, FludarabinePatients will receive a NMA-LD chemotherapy based on Cyclophosphamide 60 mg/kg IV (once daily on Days -5 and -4) and Fludarabine 25 mg/m2 IV (once daily on Days -5 to -1). | Drug | NEXTGEN-TIL |
| Interleukin-2Also: IL-2, AldesleukinPatients will receive sequential doses of 720,000 IU/kg IV IL-2 every 8-24 hours depending on patient tolerance. It will be administered on Days 0 to 2, starting between 3 and 24 hours after the completion of NEXTGEN-TIL infusion. IL-2 doses may be skipped in case of toxicity. If 2 sequential doses or more than 2 non-sequential doses of IL-2 are skipped due to patient intolerance or the discretion of the investigator, IL-2 administration must be stopped. | Drug | NEXTGEN-TIL |
Primary outcome
Incidence of Adverse Events (AE)
Time frame: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first
Nature and frequency of AE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Incidence of Serious Adverse Events (SAE)
Time frame: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first
Nature and frequency of SAE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Treatment-limiting Toxicity (TLT)
Time frame: From the first dose of study treatment (Day -5) to 30 days after
Toxicities related to treatment administration that, if recurrent at high enough frequency (≥2 patients treated), should trigger review by the Independent Data Safety Monitoring Board (IDSMB), which could lead to recommendations for treatment modifications for subsequent patients.
Incidence of alterations in clinical laboratory test results
Time frame: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in clinical laboratory test results
Incidence of alterations in electrocardiogram assessment
Time frame: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in electrocardiogram
Incidence of alterations in vital signs measurements
Time frame: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in vital signs.
Incidence of physical examination findings
Time frame: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in the physical examination.
Assessment of performance status
Time frame: From baseline through study completion, an average of 2 years
Patient performance status assessed as per Eastern Cooperative Oncology Group (ECOG) score, where grade 0 is for fully active and capable patient and grade 5 is death.
4 secondary outcomes
Neoantigen-selected TIL analysis
Time frame: At baseline
Overall Response Rate (ORR)
Time frame: From baseline through disease progression, assessed up to 36 months after last dose of IL-2
Duration of Response (DOR)
Time frame: From baseline through disease progression, assessed up to 36 months after last dose of IL-2
Progression-Free Survival (PFS)
Time frame: From baseline through disease progression, assessed up to 36 months after last dose of IL-2
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 7 Nov 2024.
- Individual participant dataSharing planned: No
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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.
Susana Muñoz contact
Elena Garralda principal investigator
Vall d'Hebron Institute of Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing NEXTGEN-TIL, Non-myeloablative Lymphodepletion (NMA-LD) Regimen and Interleukin-2 in people with Epithelial Tumors, Malignant and Malignant Solid Tumor, run by Vall d'Hebron Institute of Oncology at 1 site in Spain.
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 44 inclusion and 23 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: looking for participants now, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Elena Garralda (0034 93 489 30 00, egarralda@vhio.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events (AE) (time frame: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first). The study lists 8 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 7 Nov 2024.