Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
LN-145, Cell Therapy, Autologous Adoptive Cell Transfer, Autologous Adoptive Cell Therapy, Cellular Immuno-therapy, Tumor Infiltrating Lymphocytes, TIL, IL-2, LN-145-S1
Brief summary
Multicenter, multicohort, non-randomized, prospective, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145/LN-145-S1) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck
Detailed description
LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. The cell transfer therapy used in this study involves patients receiving a NMA lymphodepletion preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.
Interventions
BIOLOGICALLN-145
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
BIOLOGICALLN-145-S1
A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration.
Sponsors
Iovance Biotherapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be greater than 18 years of age at the time of consent. * Must have recurrent and/or metastatic, squamous cell carcinoma of the head and neck (both HPV-positive and -negative) * Must have at least 1 lesion that is resectable for TIL generation. * Must have measurable disease as defined by RECIST v1.1 following the surgical resection. * Must have received at least 1 and no more than 3 lines of prior systemic immunotherapy and/or chemotherapeutic treatments for HNSCC. * Any prior therapy directed at the malignant tumor must be discontinued at least 28 days prior to lymphodepletion. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Patients must be seronegative for the human immunodeficiency virus. * Patients seropositive for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment * Patients of childbearing potential and patients whose sexual partners are of childbearing potential must be willing to practice an approved method of highly effective birth control starting at the time of informed consent and for 1 year after the completion of the study treatment regimen.
Exclusion criteria
* Patients who have received an organ allograft or prior cell transfer therapy within the past 20 years. * Patients who are on a systemic steroid therapy (greater than 10 mg of prednisone or equivalent). Patients receiving steroids as replacement therapy for adrenocortical insufficiency at \< 10 mg of prednisone or other steroid equivalent daily may be eligible. * Prior therapy-related toxicities Grade ≥ 1 according to Common Toxicity Criteria for Adverse Events (CTCAE) v4.03 * Patients with documented Grade ≥ 2 diarrhea or colitis as a result of previous immunotherapy within six months from screening. * Patients who have a contraindication to or history of hypersensitivity reaction to cyclophosphamide, mesna, fludarabine, IL-2, antibiotics of the aminoglycoside group (ie, gentamicin or streptomycin; excluding those who are skin-test negative for gentamicin hypersensitivity), any component of the TIL infusion product formulation including dimethylsulfoxide (DMSO), human serum albumin (HSA), IL-2, and dextran-40. * Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system. * Patients with symptomatic and/or untreated brain metastases. * Have any form of primary or acquired immunodeficiency syndrome, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS). * Patients who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association (NYHA) Class 2 or higher. * Patients who have had another primary malignancy within the previous 3 years. * Patients who are pregnant, parturient, or breastfeeding women. * Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD regimen.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 24 months | The percentage of patients who have a confirmed complete response or partial response as assessed by the investigator per RECIST v1.1. Objective response rate (ORR) will be defined as the percentage of the patients with a confirmed complete or partial response (CR or PR),by MRI or CT scan as per RECIST 1.1 criteria. Complete response (CR), Disappearance of all target and non-target lesions. All lymph nodes must be non-pathological in size(\<10mm short axis). No new lesions. Partial response (PR), At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance above the normal limits (Non-CR/Non-PD). No new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | Up to 24 months | To evaluate efficacy parameters such as Duration of Response (DOR) using RECIST v1.1 as assessed by the Investigator. DOR is measured from the time point at which the initial measurement criteria per RECIST v1.1 are met for a CR or PR (if response is a confirmed response), whichever response is observed first, until PD. |
| Disease Control Rate | Up to 24 months | The percentage of patients who have a best overall response of complete response, partial response, or stable disease as assessed by the investigator per RECIST v1.1. The BOR of SD must be at least 4 weeks from LN-145/LN-145-S1 infusion. |
| Progression-Free Survival | Up to 24 months | The time (in months) from the date of the TIL infusion to progressive disease as assessed by the Investigator using RECIST v1.1 or death due to any cause, whichever occurs earlier. Progression was defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of diameters of the target lesions and an absolute increase of at least 5 mm, and/or unequivocal progression of existing non-target lesions, and/or the appearance of 1 or more new lesions. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 20 centers that screened participants and 18 that enrolled participants in the United States, Jan 2017 through Aug 2022.
Pre-assignment details
No participants were enrolled in Cohort 5 (TIL Retreatment Cohort) thus Cohort 5 (TIL Retreatment Cohort) has zero participants.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Treatment with LN-145, Generation 1 (Gen 1), non-cryopreserved TIL
LN-145: A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration. | 8 |
| Cohort 2 Treatment with LN-145 Generation 2 (Gen 2), cryopreserved TIL
LN-145: A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration. | 17 |
| Cohort 3 Treatment with LN-145 Generation 3 (Gen 3), cryopreserved TIL
LN-145: A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration. | 16 |
| Cohort 4 Treatment with LN-145-S1 cryopreserved TIL
LN-145-S1: A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration. | 12 |
| Cohort 5 LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment
LN-145: A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.
LN-145-S1: A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After NMA lymphodepletion, patients are infused with autologous TIL (LN-145-S1) followed by IL-2 administration. | 0 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Death | 6 | 15 | 13 | 9 | 0 |
| Overall Study | Did Not Receive TIL | 2 | 5 | 3 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Sponsor Terminated Study | 0 | 1 | 2 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Cohort 3 | Cohort 4 | Cohort 5 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 7 Participants | 4 Participants | 2 Participants | 0 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 10 Participants | 12 Participants | 10 Participants | 0 Participants | 40 Participants |
| Age, Continuous | 57 years | 58 years | 56 years | 56.5 years | — | 57 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 2 Participants | — | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 17 Participants | 14 Participants | 10 Participants | — | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | — | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 2 Participants | — | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 1 Participants | — | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | — | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 16 Participants | 15 Participants | 9 Participants | — | 48 Participants |
| Region of Enrollment United States | 8 participants | 17 participants | 16 participants | 12 participants | — | 53 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 2 Participants | — | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 14 Participants | 10 Participants | — | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 8 | 15 / 17 | 13 / 16 | 9 / 12 | 0 / 0 |
| other Total, other adverse events | 8 / 8 | 17 / 17 | 16 / 16 | 12 / 12 | 0 / 0 |
| serious Total, serious adverse events | 5 / 8 | 9 / 17 | 11 / 16 | 8 / 12 | 0 / 0 |
Outcome results
Primary
Objective Response Rate
The percentage of patients who have a confirmed complete response or partial response as assessed by the investigator per RECIST v1.1. Objective response rate (ORR) will be defined as the percentage of the patients with a confirmed complete or partial response (CR or PR),by MRI or CT scan as per RECIST 1.1 criteria. Complete response (CR), Disappearance of all target and non-target lesions. All lymph nodes must be non-pathological in size(\<10mm short axis). No new lesions. Partial response (PR), At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance above the normal limits (Non-CR/Non-PD). No new lesions.
Time frame: Up to 24 months
Population: The Full Analysis Set is defined as patients who have received LN-145/LN-145-S1 infusion that meets the manufacturing product specification.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Objective Response Rate | 37.5 percentage of patients |
| Cohort 2 | Objective Response Rate | 5.9 percentage of patients |
| Cohort 3 | Objective Response Rate | 0 percentage of patients |
| Cohort 4 | Objective Response Rate | 16.7 percentage of patients |
Secondary
Disease Control Rate
The percentage of patients who have a best overall response of complete response, partial response, or stable disease as assessed by the investigator per RECIST v1.1. The BOR of SD must be at least 4 weeks from LN-145/LN-145-S1 infusion.
Time frame: Up to 24 months
Population: The Full Analysis Set is defined as patients who have received LN-145/LN-145-S1 infusion that meets the manufacturing product specification.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Disease Control Rate | 87.5 percentage of patients |
| Cohort 2 | Disease Control Rate | 70.6 percentage of patients |
| Cohort 3 | Disease Control Rate | 75.0 percentage of patients |
| Cohort 4 | Disease Control Rate | 75.0 percentage of patients |
Secondary
Duration of Response
To evaluate efficacy parameters such as Duration of Response (DOR) using RECIST v1.1 as assessed by the Investigator. DOR is measured from the time point at which the initial measurement criteria per RECIST v1.1 are met for a CR or PR (if response is a confirmed response), whichever response is observed first, until PD.
Time frame: Up to 24 months
Population: Participants who had confirmed responses from the Full Analysis Set. The Full Analysis Set is defined as patients who have received LN-145/LN-145-S1 infusion that meets the manufacturing product specification.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Response | 3.1 Months |
| Cohort 2 | Duration of Response | NA Months |
| Cohort 4 | Duration of Response | NA Months |
Secondary
Progression-Free Survival
The time (in months) from the date of the TIL infusion to progressive disease as assessed by the Investigator using RECIST v1.1 or death due to any cause, whichever occurs earlier. Progression was defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of diameters of the target lesions and an absolute increase of at least 5 mm, and/or unequivocal progression of existing non-target lesions, and/or the appearance of 1 or more new lesions.
Time frame: Up to 24 months
Population: The Full Analysis Set is defined as patients who have received LN-145/LN-145-S1 infusion that meets the manufacturing product specification.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Progression-Free Survival | 2.8 Months |
| Cohort 2 | Progression-Free Survival | 1.9 Months |
| Cohort 3 | Progression-Free Survival | 2.8 Months |
| Cohort 4 | Progression-Free Survival | 1.9 Months |