Autologous Tumor Infiltrating Lymphocytes MDA-TIL In Treating Patients With Recurrent Or Refractory Ovarian Cancer, Colorectal Cancer, Or Pancreatic Ductal Adenocarcinoma

Study Overview

Autologous Tumor Infiltrating Lymphocytes MDA-TIL in Treating Patients With Recurrent or Refractory Ovarian Cancer, Colorectal Cancer, or Pancreatic Ductal Adenocarcinoma

This phase II trial studies how well autologous tumor infiltrating lymphocytes MDA-TIL works in treating patients with ovarian cancer, colorectal cancer, or pancreatic ductal adenocarcinoma that has come back (recurrent) or does not respond to treatment (refractory). Autologous tumor infiltrating lymphocytes MDA-TIL, made by collecting and growing specialized white blood cells (called T-cells) from a patient's tumor, may help to stimulate the immune system in different ways to stop tumor cells from growing.

PRIMARY OBJECTIVE: I. To evaluate efficacy using objective response rate (ORR) using the Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 in subjects with ovarian cancer, pancreatic ductal adenocarcinoma (PDAC), and colorectal cancers. SECONDARY OBJECTIVES: I. Determine the disease control rate (DCR) within and across cohorts. II. Determine the duration of response (DOR). III. Determine progression-free survival (PFS) and overall survival (OS). IV. Further characterize the safety profile of adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) across multiple tumor types. EXPLORATORY OBJECTIVES: I. Establish duration of TIL persistence. II. Compare the molecular and immunological features of tumors before and after TIL therapy. III. Prospectively evaluate the existing immunotherapy response criteria (immune-related Response Evaluation Criteria in Solid Tumors [irRECIST]) as the best response assessment tool for TIL therapy among a diverse group of solid tumors. IV. Investigate TIL attributes (CD8 %, CD27 and CD28 expression) and correlation with response to therapy. V. Assess tumor marker (CA19-9; CA-125) response in patients who produce this tumor marker. VI. Assess Health-Related Quality of Life (HRQOL). OUTLINE: LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -7 and -6, and fludarabine IV over 15-30 minutes on days -5 to -1 in the absence of disease progression or unacceptable toxicity. T-CELL INFUSION: Patients receive autologous tumor infiltrating lymphocytes MDA-TIL IV over 45 minutes on day 0. Patients then receive IL-2 IV over 30 minutes on days 1-4 for up to 6 doses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at week 18, at 6, 9, 12, 18, and 24 months, and then every 3 months for up to 3 years.

Malignant Solid Neoplasm
Metastatic Colorectal Adenocarcinoma
Metastatic Ovarian Carcinoma
Metastatic Pancreatic Ductal Adenocarcinoma
Platinum-Resistant Ovarian Carcinoma
Recurrent High Grade Ovarian Serous Adenocarcinoma
Recurrent Ovarian Carcinosarcoma
Refractory Colorectal Carcinoma
Stage IV Colorectal Cancer AJCC v8
Stage IVA Colorectal Cancer AJCC v8
Stage IVB Colorectal Cancer AJCC v8
Stage IVC Colorectal Cancer AJCC v8

BIOLOGICAL: Autologous Tumor Infiltrating Lymphocytes MDA-TIL
DRUG: Cyclophosphamide
DRUG: Fludarabine
BIOLOGICAL: Interleukin-2
OTHER: Quality-of-Life Assessment

2017-0671
NCI-2018-01509 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
2017-0671 (OTHER Identifier) (OTHER: M D Anderson Cancer Center)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2018-07-24	Results First Submitted 2024-12-12	Last Update Submitted that met QC Criteria 2025-04-01
First Submitted that Met QC Criteria 2018-07-31	Results First Submitted that Met QC Criteria 2025-04-01	Last Update Posted (ACTUAL) 2025-04-17
First Posted (ACTUAL) 2018-08-01	Results First Posted 2025-04-17	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (autologous tumor infiltrating lymphocytes MDA-TIL) LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, and fludarabine IV over 15-30 minutes on days -5 to -1 in the absence of disease progression or unacceptable toxicity. T-CELL INFUSION: Patients receive autolog	BIOLOGICAL: Autologous Tumor Infiltrating Lymphocytes MDA-TIL Given IV DRUG: Cyclophosphamide Given IV DRUG: Fludarabine Given IV BIOLOGICAL: Interleukin-2 Given IV OTHER: Quality-of-Life Assessment Ancillary studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (autologous tumor infiltrating lymphocytes MDA-TIL)

LYMPHODEPLETION REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6, and fludarabine IV over 15-30 minutes on days -5 to -1 in the absence of disease progression or unacceptable toxicity. T-CELL INFUSION: Patients receive autolog

BIOLOGICAL: Autologous Tumor Infiltrating Lymphocytes MDA-TIL

Given IV

DRUG: Cyclophosphamide

Given IV

DRUG: Fludarabine

Given IV

BIOLOGICAL: Interleukin-2

Given IV

OTHER: Quality-of-Life Assessment

Ancillary studies

Primary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR) in Participants With Ovarian Cancer (OVCA), PDAC (Pancreatic Cancer), and Colorectal Cancers (CRC) According to RECIST v1.1 in Subjects With Ovarian Cancer (OVCA), PDAC (Pancreatic Cancer), and Colorectal Cancers (CRC)	The ORR is derived as the sum of the number of patients with a confirmed CR or partial response (PR) divided by the number of patients in the All-Treated analysis set x 100%.	Through 4 years

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants With Stable Disease	Participants will be evaluated at 6 and 12 weeks for response.	6 weeks, 12 weeks
Progression-free Survival (PFS) and Overall Survival (OS)		44.8 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Subjects must be willing and able to provide informed consent
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1 at enrollment and within 7 days of initiating lymphodepleting chemotherapy
Subjects must have an area of tumor amenable to excisional biopsy (core biopsies may be allowed) for the generation of TIL separate from, and in addition to, a target lesion to be used for response assessment
Any prior therapy directed at the malignant tumor, including radiation therapy, chemotherapy, and biologic/targeted agents must be discontinued at least 28 days prior to tumor resection for preparing TIL therapy
Absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days of enrollment)
Hemoglobin >= 9.0 g/dL (transfusion allowed) (within 7 days of enrollment)
Platelet count >= 100,000/mm^3 (within 7 days of enrollment)
Alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) and aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 x the upper limit of normal (ULN)

Patients with liver metastases may have liver function test [LFT] =< 5.0 x ULN (within 7 days of enrollment)
Calculated creatinine clearance (Cockcroft-Gault) >= 50.0 mL/min (within 7 days of enrollment)
Total bilirubin =< 1.5 x ULN (within 7 days of enrollment)
Prothrombin time (PT) & activated partial thromboplastin time (aPTT) =< 1.5 x ULN (correction with vitamin K allowed) unless subject is receiving anticoagulant therapy (which should be managed according to institutional norms prior to and after excisional biopsy) (within 7 days of enrollment)
Negative serum pregnancy test (female subjects of childbearing potential) (within 7 days of enrollment)
Subjects must not have a confirmed human immunodeficiency virus (HIV) infection
Subjects must have a 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms
Subjects must also have a negative dobutamine stress echocardiogram before beginning treatment
Subjects of childbearing potential must be willing to practice an approved highly effective method of birth control starting at the time of informed consent and for 1 year after the completion of the lymphodepletion regimen. Approved methods of birth control are as follows: hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation or hysterectomy; subject/partner status post vasectomy; implantable or injectable contraceptives; and condoms plus spermicide
Able to adhere to the study visit schedule and other protocol requirements
Pulmonary function tests (spirometry) demonstrating forced expiratory value (FEV) 1 greater than 65% predicted or forced vital capacity (FVC) greater than 65% of predicted
Ovarian cancer cohort only: Subjects must have high grade non-mucinous histology (carcinosarcomas are allowed)
Ovarian cancer cohort only: Subjects must have failed at least two prior lines of chemotherapy (i.e. frontline adjuvant chemotherapy plus one additional line for recurrent/progressive disease), or have platinum resistant disease
Colorectal cohort only: Subjects with colorectal adenocarcinoma must have metastatic disease that is considered incurable with currently available therapies and have derived maximal benefit from or have become refractory to frontline conventional therapy (e.g. leucovorin calcium [calcium folinate], 5-fluorouracil and oxaliplatin [FOLFOX], leucovorin calcium, 5-fluorouracil, and irinotecan [FOLFIRI]).
Colorectal cohort only: Subjects should have low disease burden such that in the treating physician's opinion the patient would not require additional intervening treatment for 7-8 weeks (required for TIL harvest and manufacturing)
Pancreatic adenocarcinoma cohort only: Subjects must have histologically or cytologically documented diagnosis of PDAC with oligo-metastatic disease
Pancreatic adenocarcinoma cohort only: Subjects must have progressed on, or received maximal benefit from, front-line therapy
Pancreatic adenocarcinoma cohort only: Patients may have received unlimited lines of prior standard of care therapy
Pancreatic adenocarcinoma cohort only: Patients with ascites or carcinomatosis are not eligible for the study
Pancreatic adenocarcinoma cohort only: Patients will need an albumin of >= 3.0 mg/dL within 7 days of enrollment
TREATMENT INCLUSION CRITERION: Within 24 h of starting lymphodepleting chemotherapy, subjects must meet the following laboratory criteria:

Absolute neutrophil count (ANC) >= 1000/mm^3
Hemoglobin >= 9.0 g/dL (transfusion allowed)
Platelet count >= 100,000/mm3
ALT/SGPT and AST/SGOT =< 2.5 x the upper limit of normal (ULN)

Patients with liver metastases may have liver function tests (LFT) =< 5.0 x ULN
Calculated creatinine clearance (Cockcroft-Gault) >= 50.0 mL/min
Total bilirubin =< 1.5 X ULN

Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system. Principal investigator (PI) or his/her designee shall make the final determination regarding appropriateness of enrollment
Patients with active viral hepatitis
Patients who have a left ventricular ejection fraction (LVEF) < 45% at screening
Patients with a history of prior adoptive cell therapies
Persistent prior therapy-related toxicities greater than grade 2 according to Common Toxicity Criteria for Adverse Events (CTCAE) v. 4.03, except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment
Primary immunodeficiency
History of organ or hematopoietic stem cell transplant
Chronic steroid therapy, however prednisone or its equivalent is allowed at < 10 mg/day
Patients who are pregnant or nursing
Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his/her designee, would prevent adequate informed consent
History of clinically significant autoimmune disease including active, known, or suspected autoimmune disease. Subjects with resolved side effects from prior checkpoint inhibitor therapy, vitiligo, psoriasis, type 1 diabetes or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded
History of clinically significant chronic obstructive pulmonary disease (COPD), asthma, or other chronic lung disease
History of a second malignancy (diagnosed in the last 5 years). Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
History of known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to initiation of lymphodepletion
Has received a live vaccine within 30 days prior to the initiation of lymphodepletion
Patients who have a contraindication to or history of hypersensitivity reaction to any components or excipients of the TIL therapy or the other study drugs: NMA-LD (cyclophosphamide, mesna, and fludarabine); IL-2; any component of the TIL infusion product formulation including human serum albumin (HSA), IL-2, and dextran-40
Any other condition that in the investigator's judgement would significantly increase the risks of participation
Patient has any complication or delayed healing from excisional procedure that in the investigator's opinion would increase the risks of lymphodepletion, adoptive TIL therapy and adjuvant IL-2
Patients has a decline in performance status to ECOG > 1 (at the visit prior to admission for lymphodepletion)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Bristol-Myers Squibb
Iovance Biotherapeutics
National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Amir A Jazaeri, M.D. Anderson Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Amaria R, Knisely A, Vining D, Kopetz S, Overman MJ, Javle M, Antonoff MB, Tzeng CD, Wolff RA, Pant S, Lito K, Rangel K, Fellman B, Yuan Y, Lu KH, Sakellariou-Thompson D, Haymaker CL, Forget MA, Hwu P, Bernatchez C, Jazaeri AA. Efficacy and safety of autologous tumor-infiltrating lymphocytes in recurrent or refractory ovarian cancer, colorectal cancer, and pancreatic ductal adenocarcinoma. J Immunother Cancer. 2024 Feb 2;12(2):e006822. doi: 10.1136/jitc-2023-006822.
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

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