Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Lung Neoplasms

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Pembrolizumab

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Ipilimumab

Immunoglobulins

Mitogens

Antibodies, Blocking

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

LN-144 therapy in combination with pembrolizumab in patients with Stage IIIC to IV unresectable or metastatic melanoma with ≤ 3 prior lines of systemic therapy, excluding checkpoint inhibitors (CPI).

LN-145-S1 therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is proto-oncogene B-Raf (BRAF) V600 mutation positive, patients must have received a BRAF inhibitor with or without a mitogen-activated extracellular signal-related kinase (MEK) inhibitor.

LN-144 Generation 3 (Gen 3) therapy as a single agent in patients with Stage IIIC or Stage IV unresectable or metastatic melanoma, who have previously received systemic therapy with a PD-1 blocking antibody. If the tumor is BRAF V600 mutation positive, patients must have received BRAF inhibitor with or without a MEK inhibitor.

LN-145 therapy in combination with pembrolizumab in patients with advanced, recurrent, or metastatic HNSCC, with ≤ 3 prior lines of systemic therapy, excluding CPIs.

LN-145 therapy in combination with pembrolizumab in patients with locally advanced or metastatic (Stage III or Stage IV) non-small-cell lung cancer (NSCLC) with ≤ 3 prior lines of systemic therapy, excluding CPIs, or ≤ 4 lines if 2 or more of the lines are TKI therapy for those with tumors that harbored actionable mutations (eg, EGFR, ALK, ROS).

LN-145 therapy as a single agent in patients with Stage III or Stage IV NSCLC, who have previously received 1-3 lines of prior systemic therapy. Patients with known oncogene drivers (eg, EGFR, ALK, ROS) who have mutations that are sensitive to targeted therapies are not required to have received prior systemic therapy with CPIs.

LN-145 therapy in combination with ipilimumab and nivolumab in patients with Stage III or Stage IV NSCLC who have previously received 1 line of CPI monotherapy. No other systemic therapy for metastatic disease is allowed. Prior chemoradiation and/or chemotherapy in the adjuvant and/or neo-adjuvant settings are allowed.

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 Lifileucel followed by IL-2 administration. Lifileucel will be administered to patients once (on Day 0) during the study.

Lifileucel

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. TIL will be administered to patients once (on Day 0) during the study.

LN-145

Humanized antibody.

Pembrolizumab will be administered following tumor resection and will continue every 3 weeks or every 6 weeks thereafter for up to 2 years.

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-S1) followed by IL-2 administration. TIL will be administered to patients once (on Day 0) during the study.

LN-145-S1

Monoclonal antibody

Ipilimumab will be administered as a single dose prior to tumor resection.

Monoclonal antibody

Nivolumab will be administered once prior to tumor resection. The second dose will be administered prior to TIL administration and dosing will continue every 4 weeks for up to 2 years.

Iovance Biotherapeutics Study Team

Iovance Biotherapeutics Medical Monitor

A prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study evaluating adoptive cell therapy (ACT) with TIL LN-144 (Lifileucel)/LN-145 in combination with checkpoint inhibitors or TIL LN-144 (Lifileucel)/LN-145/LN-145-S1 as a single agent therapy.

LN-144 (Lifileucel)/LN-145/LN-145-S1 is an adoptive cell transfer therapy that utilizes an autologous TIL for the treatment of patients with unresectable or metastatic melanoma, advanced, recurrent, or metastatic squamous cell carcinoma of the head and neck, and locally advanced or metastatic non-small cell lung cancer. The adoptive cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphodepletion regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2. Patients in Cohorts 1A, 2A, 3A and 3C will receive TIL plus checkpoint inhibitors. Patients in Cohorts 1B, 1C, and 3B will receive autologous TIL as a single therapy.

Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors

A Phase 2, Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (LN 144/LN-145/LN-145-S1) in Patients With Solid Tumors

To evaluate the efficacy of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as determined by objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Investigator

To characterize the safety profile of autologous TIL in combination with CPIs in metastatic melanoma, HNSCC, and NSCLC patients and as a single therapy in metastatic melanoma and NSCLC patients as measured by the incidence of Grade ≥ 3 treatment-emergent adverse events (TEAEs)

To evaluate efficacy parameters such Complete Response (CR) rate per RECIST 1.1, as assessed by the Investigator

To evaluate efficacy parameters such Duration of Response (DOR) per RECIST 1.1, as assessed by the Investigator

To evaluate efficacy parameters such Disease Control Rate (DCR) per RECIST 1.1, as assessed by the Investigator

To evaluate efficacy parameters such Progression-Free Survival (PFS) per RECIST 1.1, as assessed by the Investigator

To evaluate efficacy parameters such Overall Survival (OS)

Iovance Biotherapeutics, Inc.

Symptoms and General Pathology

Rare Diseases

Recurrence

Lung Diseases

Skin Neoplasms

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Participants with unresectable or metastatic melanoma

Participants with Stage III or IV non-small-cell lung cancer

A tumor sample is resected from each participant and cultured ex-vivo to manufacture IOV-4001. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, participant is infused with IOV-4001, and followed by IL-2.

IOV-4001

This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non-small-cell lung cancer (NSCLC).

This study is the first-in-human study of IOV-4001, a genetically modified autologous tumor- infiltrating lymphocytes (TIL) product. IOV-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited TIL, but with the potential for enhanced antitumor activity due to disruption of PDCD1, the gene for programmed cell death protein-1 (PD-1).

A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer

A Phase 1/2, Open-label Study of PD-1 Knockout Tumor-infiltrating Lymphocytes (IOV-4001) in Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer

The safety of IOV-4001 will be assessed based on the totality of dose-limiting toxicity (DLT) and adverse event (AE) data collected during this phase

To evaluate the proportion of participants who have a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by the investigator

To evaluate the proportion of participants who have a confirmed CR per RECIST v1.1 as assessed by the investigator

To evaluate the duration from the time that criteria are met for CR or PR per RECIST v1.1 as assessed by the investigator until disease progression or death due to any cause

To evaluate the percentage of participants with a best overall confirmed response of CR or PR at any time plus stable disease (SD) per RECIST v1.1 as assessed by the investigator

To evaluate the time from the date of IOV-4001 infusion until disease progression per RECIST v1.1 as assessed by the investigator or death due to any cause

To evaluate the time from the date of IOV-4001 infusion to death due to any cause.

This will be characterized by the severity, seriousness, relationship to study treatment, and characteristics of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), study intervention-related adverse events (AEs), and AEs.

This will be assessed by the proportion of participants who had tumor harvested and were treated without manufacturing delay or failure.

Lifileucel (LN-144) without cryopreservation (Gen 1 infusion product) (Closed)

Cryopreserved lifileucel (LN-144) (Gen 2 infusion product) (Closed)

Retreatment cohort: patients from Cohort 1, Cohort 2 or Cohort 4 may rescreen for a second TIL regimen therapy if they meet all Inclusion and Exclusion Criteria (except exclusion criterion b).

Cryopreserved lifileucel (LN-144) (Gen 2 infusion product)

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepletion, patients are infused with Lifileucel followed by IL-2.

Prospective, interventional multicenter study evaluating adoptive cell therapy (ACT) via infusion of LN-144 (autologous TIL) followed by interleukin 2 (IL-2) after a nonmyeloablative lymphodepletion (NMA LD) preconditioning regimen.

Lifileucel is an autologous adoptive cell transfer therapy that utilizes a TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with metastatic melanoma. The adoptive cell transfer therapy used in this study involves patients receiving a lymphocyte depleting preconditioning regimen, prior to infusion of autologous TIL, followed by the administration of a regimen of IL-2.

Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma

A Phase 2, Multicenter Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-144) for Treatment of Patients With Metastatic Melanoma

Evaluate the efficacy of LN-144 in patients with unresectable or metastatic melanoma using the objective response rate (ORR), as assessed by the Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Evaluate the efficacy endpoints of duration of response (DOR) by the BIRC and by the investigator per RECIST v1.1

Evaluate the efficacy endpoints of disease control rate (DCR) as assessed by the BIRC and by the investigator per RECIST v1.1

Evaluate the efficacy endpoints of progression-free survival (PFS) as assessed by the BIRC and by the investigator per RECIST v1.1

Evaluate overall survival (OS) and objective response rate (ORR) by the investigator

Incidence rate of treatment-emergent adverse events (AEs) and serious AEs by severity and relationship to Lifileucel (LN-144).

Melanoma, Cutaneous Malignant

Tin Fluorides

Patients who relapsed after or were refractory to at least 1 prior line of systemic therapy including a PD-1 inhibitor.

Patients who were intolerant to a PD-1 inhibitor and have persistent disease after stopping PD-1 therapy.

Patients who had a best response of stable disease despite being treated with at least 4 doses of a PD-1 inhibitor in the previous line of therapy.

ITIL-168 is a cell therapy product derived from a patient's own TILs. A tumor sample is removed from each patient to make a personalized ITIL-168 product. Once ITIL-168 has been made, the patient is treated with 5 days of lymphodepleting chemotherapy including cyclophosphamide and fludarabine, followed by a single infusion of ITIL-168, and up to 8 doses of IL-2.

ITIL-168

Instil Study Director

DELTA-1 is a phase 2 clinical trial to evaluate the efficacy and safety of ITIL-168 in adult subjects with advanced melanoma who have previously been treated with a PD-1 inhibitor. ITIL-168 is a cell therapy derived from a patient's own tumor-infiltrating immune cells (lymphocytes; TILs).

All enrolled participants are assigned to be treated with a single dose of ITIL-168

ITIL-168 in Advanced Melanoma

A Phase 2, Open-label, Multicenter Study Evaluating the Safety and Efficacy of Autologous Tumor-infiltrating Lymphocytes (TILs) in Subjects With Advanced Melanoma (DELTA-1)

Objective response rate (ORR), defined as the incidence of a complete response (CR) or a partial response (PR) per a modified Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria, as assessed by central review.

For subjects who experience an objective response, duration of response (DOR) is defined as the time from their first objective response to disease progression or death.

Progression-free survival (PFS) is defined as the time from the ITIL-168 infusion date to the date of disease progression or death from any cause.

Overall survival (OS) is defined as the time from the ITIL-168 infusion date to the date of death from any cause.

ORR as determined by investigators is defined as the incidence of a CR or a PR per a modified RECIST v1.1, as determined by study investigators.

Disease control rate (DCR), defined as the incidence of CR, PR, or stable disease (SD) per a modified RECIST v1.1 criteria, as determined by central review.

Instil Bio

Durvalumab

After nonmyeloablative (NMA) lymphodepletion, patients are infused with their autologous TIL (LN-145) followed by IL-2 administration.

adoptive cell therapy (ACT) with autologous TIL therapy

Iovance Medical Monitor

This study is a Phase 2, open-label, multicenter study evaluating adoptive cell therapy (ACT) with autologous TIL therapy (LN-145) in combination with Anti-PD-L1 inhibitor durvalumab.

LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI. The cell transfer therapy used in this study involves patients receiving a nonmyeloablative (NMA) lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combo With Durvalumab in Non-Small Cell Lung Cancer

A Phase 2 Study to Assess the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combination With Anti-PD-L1 Inhibitor Durvalumab (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

To evaluate efficacy using the objective response rate (ORR)

To evaluate the safety as measured by any ≥ Grade 3 treatment-emergent adverse event (TEAE) rate

To further evaluate efficacy such as the duration of response (DOR)

To further evaluate efficacy such as progression free survival (PFS)

To further evaluate efficacy such as overall survival (OS)

Neoplasms, Squamous Cell

Treatment with LN-145, Generation 1 (Gen 1), non-cryopreserved TIL

Treatment with LN-145 Generation 2 (Gen 2), cryopreserved TIL

Treatment with LN-145 Generation 3 (Gen 3), cryopreserved TIL

Treatment with LN-145-S1 cryopreserved TIL

LN-145 cryopreserved/LN-145-S1 cryopreserved TIL re-treatment

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.

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.

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

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.

Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck

A Phase 2, Multicenter Study to Evaluate the Efficacy and Safety of Autologous Tumor Infiltrating Lymphocytes (LN-145/LN-145-S1) for the Treatment of Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

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.

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.

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.

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.

Treatment-emergent adverse events (TEAEs), clinical laboratory data assessments, serious adverse events (SAEs), and adverse events (AEs) were collected and evaluated for the duration of the study until resolution or permanent sequelae. The Safety Analysis Set is defined as patients who have received TIL infusion.

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.

Cohort 1

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.

Cohort 2

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.

Cohort 3

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.

Cohort 4

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.

Cohort 5

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The Safety Analysis Set is defined as patients who have received LN-145/LN-145-S1 infusion.

Sr. Medical Director, Rana Fiaz

The Full Analysis Set is defined as patients who have received LN-145/LN-145-S1 infusion that meets the manufacturing product specification.

Objective Response Rate

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors	NCT03645928	Metastatic Mela... Squamous Cell C... Non-small Cell ...	Lifileucel LN-145 Pembrolizumab LN-145-S1 Ipilimumab Nivolumab	12 Years -	Iovance Biotherapeutics, Inc.
A Study to Investigate the Efficacy and Safety of an Infusion of IOV-4001 in Adult Participants With Unresectable or Metastatic Melanoma or Stage III or IV Non-small-cell Lung Cancer	NCT05361174	Unresectable Me... Metastatic Mela... Stage III Non-s... Stage IV Non-sm...	IOV-4001	18 Years -	Iovance Biotherapeutics, Inc.
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma	NCT02360579	Metastatic Mela...	Lifileucel	18 Years -	Iovance Biotherapeutics, Inc.
ITIL-168 in Advanced Melanoma	NCT05050006	Advanced Cutane...	ITIL-168	18 Years -	Instil Bio
Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combo With Durvalumab in Non-Small Cell Lung Cancer	NCT03419559	Non Small Cell ...	LN-145 Durvalumab	18 Years -	Iovance Biotherapeutics, Inc.
Study of LN-145/LN-145-S1 Autologous Tumor Infiltrating Lymphocytes in the Treatment of Squamous Cell Carcinoma of the Head & Neck	NCT03083873	Squamous Cell C...	LN-145 LN-145-S1	18 Years -	Iovance Biotherapeutics, Inc.
Study of Autologous Tumor Infiltrating Lymphocytes in Patients With Solid Tumors	NCT03645928	Metastatic Mela... Squamous Cell C... Non-small Cell ...	Lifileucel LN-145 Pembrolizumab LN-145-S1 Ipilimumab Nivolumab	12 Years -	Iovance Biotherapeutics, Inc.
ITIL-168 in Advanced Melanoma	NCT05050006	Advanced Cutane...	ITIL-168	18 Years -	Instil Bio
Study of Lifileucel (LN-144), Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma	NCT02360579	Metastatic Mela...	Lifileucel	18 Years -	Iovance Biotherapeutics, Inc.
Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) In Combo With Durvalumab in Non-Small Cell Lung Cancer	NCT03419559	Non Small Cell ...	LN-145 Durvalumab	18 Years -	Iovance Biotherapeutics, Inc.

Spots Global Cancer Trial Database for autologous adoptive cell transfer