Solid Tumours including advanced unresectable or metastatic melanoma (MM), advanced squamous cell carcinoma of the head and neck (HNSCC) and non-small cell lung cancer (NSCLC) MedDRA version: 20.0 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 10029104
Conditions
Sponsors
Iovance Biotherapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. All patients must have a histologically confirmed unresectable or metastatic melanoma (Cohort 1), recurrent or metastatic squamous cell carcinoma of the head and neck (Cohort 2, primary tumor histologic diagnosis confirmation required via pathology report), or recurrent or metastatic non-small cell lung cancer (Cohort 3). 2. Cohort 1 and Cohort 2 only: patients who have not received prior immunotherapy, including checkpoint inhibitors.With the excluded prior therapies cited, patients may have received from 1 to 3 prior systemic anticancer therapies: • In Cohort 1: Patients with unresectable or metastatic melanoma; if BRAF mutation-positive, patients may have received a BRAF inhibitor. • In Cohort 2: Patients with unresectable or metastatic HNSCC. Those who may have received initial chemo-radiotherapy are allowed. 3. Cohort 3 only: Patients with Stage III or Stage IV NSCLC (squamous, nonsquamous, adenocarcinoma, or large cell carcinoma) who have received from 1 to 3 prior systemic anticancer therapies including checkpoint inhibitors in the locally advanced or metastatic setting. 4. Patients must have at least 1 resectable lesion of a minimum 1.5 cm in diameter postresection for TIL investigational product production. It is encouraged that tumor tissue be obtained from multiple and diverse metastatic lesions, as long as the surgical resection it does not pose additional risks to the patient. 5. Patients must have a remaining measurable disease as defined by RECIST 1.1 following tumor resection for TIL manufacturing 6. Patients must be =18 years and =70 years of age at the time of consent. Enrollment of patients >70 years of age may be allowed after consultation with the Medical Monitor. 7. Patients must have an Eastern Cooperative Oncology Group performance status of 0 or 1, and an estimated life expectancy of =3 months in the opinion of the Investigator. 8. Patients of childbearing potential or their partners of childbearing potential must be willing to practice an approved method of birth control during treatment and for 12 months after receiving all protocol-related therapy 9. Patients must have the following hematologic parameters: • Absolute neutrophil count =1000/mm3; • Hemoglobin =9.0 g/dL; • Platelet count =100,000/mm3. 10. Patients must have adequate organ function: • ALT/ SGPT and AST/SGOT =3 times the upper limit of normal, patients with liver metastasis =5 times ULN; • An estimated creatinine clearance =40 mL/min using the Cockcroft Gault formula at Screening; • Total bilirubin =2 mg/dL; • Patients with Gilbert’s Syndrome must have a total bilirubin =3 mg/dL. 11. Patients must be seronegative for HIV. Patients with positive serology for hepatitis B virus surface antigen, hepatitis B core antibody, or hepatitis C virus indicating acute or chronic infection may be enrolled if the viral load by PCR is undetectable with/without active treatment. 12. Patients must have a washout period from prior anticancer therapy(ies) of a minimum duration, as detailed below prior to the first study treatment (ie, start of NMA LD) • Targeted therapy: prior targeted therapy with EGFR, MEK, BRAF, ALK, ROS1 or other-targeted agents is allowed provided the washout is a minimum of 21 days prior to the start of NMA-LD; • Chemotherapy: adjuvant, neoadjuvant or definitive chemotherapy/ chemoradiation is allowed provided the washout is a minimum of 21 days prior to the start of NMA-LD; • Immunotherapy for Cohort 3 only, prior c
Exclusion criteria
Exclusion criteria: 1. Patients with melanoma of uveal/ocular origin. 2. Patients who have received an organ allograft or prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen. Note: this criterion is not applicable for patients undergoing retreatment with TIL LN-144/LN-145. 3. Patients with symptomatic and/or untreated brain metastases, • 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 =2 weeks, 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. 4. Patients who are on a systemic steroid therapy at a dose of >10 mg of prednisone or equivalent per day. • Short course of higher-dose steroid therapy is allowed in cases of exacerbation of a known disease or for treatment of new acute symptoms not related to brain metastases. 5. Patients who are pregnant or breastfeeding. 6. Patients who have an active medical illness(es), which in the opinion of the Investigator, would pose increased risks for study participation; such as systemic infections (eg, syphilis or any other infection requiring antibiotics), coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune systems. 7. Patients may not have active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: • Patients with vitiligo or alopecia; • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; • Any chronic skin condition that does not require systemic therapy; or • Patients with celiac disease controlled by diet alone. 8. Patients who have received a live or attenuated vaccination within 28 days prior to the start of NMA-LD. 9. Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency disease [SCID] and acquired immune deficiency syndrome [AIDS]). 10. Patients with a history of hypersensitivity to any component of the study drugs. LN-144/LN-145 should not be administered to patients with a known hypersensitivity to any component of TIL product formulation including, but not limited to: • NMA-LD (cyclophosphamide, mesna, and fludarabine); • Proleukin®, aldesleukin, IL-2; • Antibiotics of the aminoglycoside group (ie, streptomycin, gentamicin); • Any component of the TIL product formulation including dimethyl sulfoxide [DMSO], human serum albumin [HSA], IL-2, and dextran-40; or • Pembrolizumab. 11. Patients who have a left ventricular ejection fraction (LVEF) <45% or who are New York Heart Association (NYHA) Class II or higher. A cardiac stress test demonstrating any irreversible wall movement abnormality in any patients =60 years of age or in patients who have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias. • Patients with an abnormal cardiac stress test may be enrolled if they have adequate ejection fraction and cardiology clea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the efficacy of autologous TIL LN-144/LN-145 as a single-therapy in NSCLC patients or in combination with pembrolizumab in MM and HNSCC patients by determining the ORR, using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by Investigator. •To characterize the safety profile of TIL LN-144/LN-145 as a single-therapy in NSCLC patients or in combination with pembrolizumab in MM and HNSCC patients as measured by the incidence of Grade =3 treatment-emergent adverse events (TEAEs). ;Secondary Objective: • To further evaluate the efficacy of autologous TIL LN-144/LN-145 as a single-therapy in NSCLC patients or in combination with pembrolizumab in MM and HNSCC patients using CR rate, durations of response (DOR), disease control rates (DCR), PFS using RECIST 1.1 as assessed by Investigator, and OS.;Primary end point(s): The ORR is defined as the proportion of patients who achieve either a confirmed PR or CR as best response as assessed by Investigators per RECIST 1.1 among the AT population. Objective response will be evaluated per each disease assessment and the ORR will be expressed as a binomial proportion with the corresponding 2-sided 90% CI. The safety primary endpoint will be measured by any Grade 3 or higher TEAE incidence rate within each cohort expressed as binomial proportions with the corresponding 2-sided 90% CI.;Timepoint(s) of evaluation of this end point: The primary analysis for each cohort will occur when all treated patients per Cohort have an opportunity to be followed for 12 months, progressed/expired, or terminated early from the post-treatment follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: The secondary efficacy endpoints are defined as follows: - CR rate is based on responders who achieved confirmed CR as assessed by Investigators. DCR is derived as the sum of the number of patients who achieved confirmed PR/CR or sustained SD (at least 6 weeks) divided by the number of patients in the efficacy analysis set × 100%. The CR rate and DCR will be summarized using a point estimate and its 2-sided 90% CI. - DOR is defined among patients who achieved objective response. It is measured from the first-time response (PR/CR) criteria are met until the first date that recurrent or progressive disease is objectively documented, or receipt of subsequent anticancer therapy or the patient dies (whichever is first recorded). Patients not experiencing PD or have not died prior to the time of data cut or the final database lock will have their event times censored on the last date that an adequate assessment of tumor status is made. - PFS is defined as the time (in months) from the time of lymphodepletion to PD, or death due to any cause, whichever event is earlier. Patients not experiencing PD or not having expired at the time of the data cut or the final database lock will have their event times censored on the last date that an adequate assessment of tumor status is made. - OS is defined as the time (in months) from the time of lymphodepletion to death due to any cause. Patients not having expired by the time of data cut or the final database lock will have their event times censored on the last date of their known survival status. - DOR, PFS, and OS will be subjected to right censoring. The Kaplan-Meier method will be used to summarize the time-to-event efficacy endpoints. The baseline data for the tumor assessment is the last scan before the lymphodepletion for all cohorts. The above efficacy parameters will be estimated for applicable cohort for subsets defined by baseline disease characteristics; BRAF status (Cohort | — |
Countries
Canada, France, Greece, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactIOV-COM-202 Study Manager
Iovance Biotherapeutics, Inc.
Outcome results
None listed