Adoptive Cell Therapy With (LN-145) in Combination With Pembrolizumab in Treating Patients With Unresectable or Metastatic Transitional Cell Cancer Who Have Failed Cisplatin-Based Chemotherapy

NCT03935347 | Withdrawn Phase 2 DMC FDA Drug

• 3 other identifiers: I 77218P30CA16056ODP30CA016056
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well autologous tumor infiltrating lymphocytes (LN-145) and pembrolizumab work in treating patients with transitional cell cancer that cannot be removed by surgery or has spread to other places in the body and have failed cisplatin-based chemotherapy. LN-145 is made up of specialized immune cells called lymphocytes or T cells that are taken from a patient's tumor, grown in a manufacturing facility and infused back into the preconditioned patient to attack the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving LN-145 may help control transitional cell bladder cancer when given together with pembrolizumab

Conditions

Metastatic Bladder Urothelial Carcinoma; Metastatic Renal Pelvis Urothelial Carcinoma; Metastatic Ureter Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Unresectable Renal Pelvis Urothelial Carcinoma; Unresectable Ureter Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  The proportion of subjects who achieve either a confirmed partial response (PR) or complete response (CR) as best response as assessed per Response Evaluation Criteria in Solid Tumors 1.1. Will be evaluated per each disease assessment and calculated with the corresponding 95% two-sided confidence interval

  Up to 3 years

Secondary Outcomes (5)

• Incidence of adverse events (AEs)

  From the first dose of cyclophosphamide up to 30 days from the last dose of IL-

• Duration of response

  Up to 3 years

• Disease Control Rate

  Up to 3 years

• Progression-free survival

  Up to 3 years

• Overall Survival

  Up to 3 years

Study Arms (1)

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

EXPERIMENTAL

Patients receive cyclophosphamide IV over 2 hours on days -8 and -7, fludarabine IV over 30 minutes on days -6 to -2, and pembrolizumab IV over 30 minutes on day -1. At least 24 hours later, patients receive autologous tumor infiltrating lymphocytes LN-145 IV on day 0, and receive aldesleukin IV over 30 minutes for up to 6 doses on days 1-4. Patients then continue receiving pembrolizumab IV over 30 minutes beginning on day 21. Cycles of pembrolizumab repeat every 21 days for 12 months in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Fludarabine Phosphate; Biological: Pembrolizumab; Biological: Autologous Tumor Infiltrating Lymphocytes LN-145; Biological: Aldesleukin

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate, 2-[bi(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate, Cyclostine, Revimmune, Syklofosfamid, WR- 138719

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

Fludarabine DRUG

Given IV

Also known as: 118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 21679-14-1, 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine, 9-Beta-D-arabinofuranosyl-2-fluoroadenine, Fluradosa

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 312887, 328002, 75607-67-9, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl, Fludarabine-5'-Monophosphate, SH T 586

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: 1374853-91-4, Immunoglobulin G4, Anti-(Human Programmed Cell Death 1)

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

Autologous Tumor Infiltrating Lymphocytes LN-145 BIOLOGICAL

Given IV

Also known as: Autologous TILs LN-145, LN-145, LN145

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

Aldesleukin BIOLOGICAL

Given IV

Also known as: 110942-02-4, 125-L-Serine-2-133-interleukin 2, Recombinant Human Interleukin-2

Treatment (cyclophosphamide, fludarabine, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject must understand the requirements of the study and voluntarily sign the informed consent form (ICF)
• All subjects must have a histologically confirmed unresectable TCC (including renal pelvis, ureters, urinary bladder, and urethra)
• Failed one and only one line of cisplatin-based chemotherapy per FDA guidelines.
• Subjects must have an area of tumor amenable to excisional biopsy for the generation of TIL separate from, and in addition to , a target lesion to be used for response assessment.Have at least one resectable lesion to generate TILs
• At least one measurable target lesion as defined by RECIST version 1.1
• An Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Estimated life expectancy of \>= 6 months
• Adequate bone marrow function
• Adequate organ function
• Subjects must be seronegative for the human immunodeficiency virus (HIV)
• Recovered from all prior anticancer therapy-related AEs to grade 1 or less
• Negative serum pregnancy test (female subjects of childbearing potential)
• Subjects of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 12 months after the completion of the study treatment regimen
• Must be able and willing to comply with the study visit schedule and protocol requirements including long-term follow-up

You may not qualify if:

• Have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or localized prostate cancer and non-melanoma skin cancer that has been adequately treated)
• Have received prior cell transfer therapy that included a nonmyeloablative or myeloablative chemotherapy regimen
• Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody, or pathway-targeting agents
• Chemotherapy or radiotherapy with projected completion within 4 weeks of initiating study treatment
• Bisphosphonate therapy for symptomatic hypercalcemia
• Have had treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-alpha or interleukin \[IL\]-2) within 6 weeks before initiation of study treatment
• Active or prior documented autoimmune or inflammatory disorders
• Subjects who have any form of human immondeficiency virus (HIV)infection
• Have severe infections within 4 weeks before initiation of study treatment
• Have received a live or attenuated vaccine within 28 days of the non-myeloablative lymphodepletion (NMA-LD regimen)
• Subjects with a history of hypersensitivity reaction(s) to any component of the LN-145 therapy and/or the other study drugs
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) \>= 450 msec for males (and \>= 470 msec for females) calculated from 3 electrocardiograms (ECGs) (within a 30-minute timeframe) or history of familiar long-QT syndrome
• Subjects who have a left ventricular ejection fraction (LVEF) \< 45% or who are New York Heart Association functional classification class II or higher
• Serious illnesses or medical conditions, which would pose increased risk for study participation and/or compliance with the protocol
• Known clinically significant liver disease

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Iovance Biotherapeutics, Inc.: collaborator

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

MeSH Terms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; pembrolizumab; Immunoglobulin G; aldesleukin

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Gurkamal Chatta, MD

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2019
• First Posted: May 2, 2019
• Study Start: June 20, 2019
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2023
• Last Updated: January 2, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)