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Brief Title: 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

Phase 2 Study of Autologous Tumor Infiltrating Lymphocytes (LN-145) With Pembrolizumab, in Subjects Who Have Failed Cisplatin-Based Chemotherapy With Locally Advanced (Unresectable) or Metastatic Transitional Cell Cancer (TCC) of the Urothelium

INTRODUCTION

  • Org Study ID: I 77218
  • Secondary ID: P30CA16056OD
  • NCT ID: NCT03935347
  • Sponsor: Roswell Park Cancer Institute

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

DETAILED DESCRIPTION


PRIMARY OBJECTIVES:

I. To evaluate the efficacy of autologous tumor infiltrating lymphocytes LN-145 (LN-145) in
combination with pembrolizumab in subjects with advanced transitional cell bladder cancer
(TCC) using the objective response rate (ORR) and the duration of response (DoR), using the
Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST version [v] 1.1).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of LN-145 in combination with pembrolizumab in subjects with TCC
based on the progression-free survival (PFS) and overall survival (OS).

II. To evaluate the safety of LN-145 in combination with pembrolizumab in subjects with TCC
based on the adverse event (AE) profile per Common Terminology Criteria for Adverse Events,
version 5.0 (CTCAE v5.0).


  • Overall Status
    Recruiting
  • Start Date
    June 20, 2019
  • Phase
    Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Objective response rate

Primary Outcome 1 - Timeframe: Up to 3 years

CONDITION

  • 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

ELIGIBILITY


Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

- Have obstructive or restrictive pulmonary disease and have a documented FEV1 (forced
expiratory volume in 1 second) of =< 60%

- Subjects with known primary central nervous system (CNS) malignancy or symptomatic CNS
metastases

- Subjects who are pregnant or breastfeeding

- Active infection including tuberculosis (TB), hepatitis B, hepatitis C, or human
immunodeficiency virus

- Treatment with any other investigational agent within 4 weeks before initiation of
study treatment

Gender: All

Minimum Age: N/A

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Gurkamal Chatta, MD

Role: Principal Investigator

Affiliation: Roswell Park Cancer Institute

Overall Contact

Name: Gurkamal Chatta, MD

Phone: 1-800-767-9355

Email: Askroswell@roswellpark.org

LOCATION

Facility Status Contact
Facility: Roswell Park Cancer Institute
Buffalo, New York 14263-0001
United States 		Status: Recruiting Contact: ASK RPCI
877-275-7724
ASKRPCI@RoswellPark.org

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