Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Lung Diseases

Recurrence

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immune Checkpoint Inhibitors

Immunomodulating Agents

Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression

Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment

Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation

Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.

Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4.

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.

LN-145

A tumor sample is obtained by image-guided core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145) followed by IL-2.

Iovance Biotherapeutics Study Team lungcelltherapy.com

Iovance Biotherapeutics Study Team

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer

LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.

Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer

To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) in patients with metastatic NSCLC using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by central review for Cohorts 1 and 2 and by the investigator for Cohorts 3, 4 and the Retreatment Cohort

To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) per RECIST v1.1, as assessed by the Investigator for Cohorts 1 and 2

To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1

To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1

To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1

To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1

To evaluate efficacy parameters such as Overall Survival (OS)

To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)

To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy

Iovance Biotherapeutics, Inc.

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

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.

Digestive System Diseases

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Micronutrients

Hematinics

Vitamins

Irinotecan

Bevacizumab

Leucovorin

Fluorouracil

Panitumumab

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

400mg/m\^2 bolus IV (in the vein) over 2-4 min, followed by 2400mg/m\^2 continuous IV over 46 hours for the first 2 cycles, increased to 3000mg/m\^2 thereafter if no significant side effects

5-Fluorouracil

This is a multi-center, open-label, randomized, phase 2, two-arm clinical trial to be conducted in the United States. Approximately 210 eligible KRAS wild-type expressing metastatic colorectal cancer subjects who have failed first-line oxaliplatin-based chemotherapy (with at least 4 doses of oxaliplatin-based chemotherapy) with at least 4 doses of bevacizumab (failure is defined as toxicity due to oxaliplatin-based chemotherapy or progression of disease on first-line treatment) will be randomized in a 1:1 ratio to receive either a once-every-two-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg or a Q2W FOLFIRI regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and institutional standard of care).

This phase 2, multicenter, open-label, randomized, two-arm study was designed to estimate the treatment effect of panitumumab in combination with FOLFIRI compared to bevacizumab in combination with FOLFIRI in subjects with metastatic colorectal cancer (mCRC) who had failed first-line therapy with at least 4 doses of oxaliplatin-based chemotherapy and bevacizumab. After data became available demonstrating that the treatment effect of antiepidermal growth factor receptor (EGFR) agents was limited to patients with wild-type Kirsten rat Sarcoma-2 virus (KRAS) mCRC, the study was amended to enroll only subjects with wild-type KRAS tumors. Eligible subjects were randomized in a 1:1 ratio to receive panitumumab 6 mg/kg plus FOLFIRI once every 2 weeks (Q2W) or bevacizumab 5 mg/kg or 10 mg/kg plus FOLFIRI Q2W. Randomization was stratified by the reason for first-line treatment failure (progression vs toxicity) and by intended bevacizumab dose (5 mg/kg vs 10 mg/kg). The intended bevacizumab doses were ascertained from sites at the time of site initiation. Subjects were treated with all or any components of second-line treatment until the occurrence of unacceptable adverse events, disease progression, death, loss to follow up, or study withdrawal by the subject, investigator, or sponsor. Tumor response was evaluated by blinded central radiology review per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 and by the investigator using either modified RECIST version 1.0 or clinical assessment. After subjects permanently discontinued all components of second-line treatment, they were to undergo a safety follow-up assessment 30 (± 7) days after the last dose. Subjects ending second-line treatment before disease progression were followed for PFS (radiographic disease assessment) every 12 weeks (± 14 days) from the safety follow-up visit until disease progression, initiation of a new therapy for mCRC, or until approximately 100 PFS events were observed in subjects with wild-type KRAS tumors. Subjects were also followed for survival every 12 weeks (± 14 days) from the safety follow-up assessment until approximately 100 PFS events were observed in subjects with wild-type KRAS tumors.

SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial

A Multi-center, Open-label, Randomized, Phase 2 Clinical Trial Evaluating Safety and Efficacy of FOLFIRI With Either Panitumumab or Bevacizumab as Second-Line Treatment in Subjects With Metastatic Colorectal Cancer With Wild-type KRAS Tumors

Progression-free survival is defined as time from the date of randomization to the date of first progression per modified RECIST version 1.0 (based on central review of the radiographic scans), or death within 60 days after the last evaluable tumor assessment or randomization date (whichever is later).

Overall survival is defined as time from the date of randomization to the date of death due to any cause. Subjects who have not died or are lost to follow-up at the analysis cutoff date will be censored at their last contact date.

Objective response rate is defined as incidence of either a confirmed complete response (CR) or partial response (PR) on study up to starting a new anti-tumor therapy and will be based on modified RECIST version 1.0 (responder) by central assessment.

Time to response is defined as time from the date of randomization to the date of first confirmed objective response

Time to progression is defined as time from the date of randomization to the date of radiographic disease progression per modified RECIST version 1.0 (per central assessment).

Disease control is defined as incidence of objective response or stable disease on study up to starting a new anti-tumor therapy.

Duration of response is defined as time from first confirmed objective response to disease progression per modified RECIST version 1.0 (by central assessment).

Amgen

The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

Summary of Adverse Events includes only those subjects who received at least one dose of investigational product.

subjects in this arm receive once-every-2-weeks (Q2W) FOLFIRI regimen plus panitumumab 6 mg/kg

Panitumumab Plus FOLFIRI

subjects in this arm receive once-every-2-weeks (Q2W) FOLFIRI regimen plus bevacizumab (either 5 mg/kg or 10 mg/kg, depending on physician choice and institutional standard of care)

Bevacizumab Plus FOLFIRI

Total

Age, Continuous

Sex: Female, Male

White or Caucasian

Black or African American

Hispanic or Latino

Asian

American Indian or Alaska Native

Other

Race/Ethnicity, Customized

0 (Fully active)

1 (Restricted in physically strenuous activity)

Missing

Scale range from 0 (fully active) to 5(dead), only status 0 or 1 is included by protocol.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Colon

Rectum

Primary tumor diagnosis

Number of metastatic organs

Study Director

Wild-type KRAS (n=91,91)

Mutant KRAS (n=36,32)

Analysis population include all enrolled subjects who received at least one dose of study therapy and do not include subjects with unevaluable KRAS status.

Progression-free Survival (PFS)

Overall Survival

Analysis population include all enrolled subjects who received at least one dose of study therapy, who had at least one baseline uni-dimensionally measurable target lesion based on central (and investigator, respectively) assessment using a modified RECIST criteria version 1.0, and who had evaluable KRAS status.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer	NCT04614103	Metastatic Non ...	LN-145 LN-145	18 Years - 70 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.
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial	NCT00418938	Cancer Colon Cancer Colorectal Canc... Metastatic Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab Leucovorin Irinotecan 5-Fluorouracil	18 Years -	Amgen
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial	NCT00418938	Cancer Colon Cancer Colorectal Canc... Metastatic Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab Leucovorin Irinotecan 5-Fluorouracil	18 Years -	Amgen
SPIRITT - Second-Line Panitumumab Irinotecan Treatment Trial	NCT00418938	Cancer Colon Cancer Colorectal Canc... Metastatic Canc... Rectal Cancer Metastatic Colo...	Panitumumab Bevacizumab Leucovorin Irinotecan 5-Fluorouracil	18 Years -	Amgen

Spots Global Cancer Trial Database for 2nd line therapy