Trial Search Results

Pilot Immunotherapy Study With Autologous T-cells Specific for NY-ESO-1/ LAGE-1a-positive Advanced NSCLC Either Alone or in Combination With Pembrolizumab

Adoptive T-cell therapy (ACT) is a therapeutic approach that uses T lymphocytes of participants with cancer, obtained by leukapheresis with the aim of generating an anti-tumor T-cell immune response. New York esophageal squamous cell carcinoma 1 (NY-ESO-1) and cancer testis antigen 2 (LAGE-1a) antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using ACT with T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses in participants with cancer. Pembrolizumab is a monoclonal antibody that acts specifically on tumor targeting T-cells and increases T-cell anti-tumor function. Pembrolizumab will be used in combination with NY-ESO-1/LAGE-1a T Cell Receptors (TCR) engineered participant T-cells (GSK3377794) to potentially further improve therapy for participants. The primary objective of the study is to evaluate the safety and tolerability of autologous genetically modified T-cells (GSK3377794) in human leukocyte antigen (HLA) positive participants with NY-ES0-1/ LAGE-1a positive advanced non-small cell lung cancer (NSCLC) alone (Arm A) or GSK3377794 in combination with pembrolizumab in participants with NSCLC with wildtype epidermal growth factor receptor (WT EGFR) and WT anaplastic lymphoma kinase/ c-ros oncogene 1 (ALK/ROS1) (Arm B) and participants with NSCLC with EGFR or ALK/ROS1 aberration (Arm C). This study consists of screening phase, Leukapheresis/ GSK3377794 manufacture, lymphodepletion/treatment phase and follow-up. Participants will receive GSK3377794 as monotherapy (Arm A); or as a combination therapy with pembrolizumab (Arm B), and participants in Arm C will receive the same treatment as participants in the Arm B. Approximately 54 participants will be enrolled into the study.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

GlaxoSmithKline

Collaborator: Merck Sharp & Dohme Corp.

Stanford Investigator(s):

Intervention(s):

  • Drug: letetresgene autoleucel
  • Drug: Pembrolizumab

Phase:

Phase 2

Eligibility


Inclusion Criteria:

Screening (Part 1):

   - The participant (or legally acceptable representative if applicable) provides written
   informed consent for the trial.

   - Participant must be positive for Human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05,
   and/or HLA-A*02:06 alleles by a validated test in a designated central laboratory.

   - Participant's tumor has been pathologically reviewed by a designated central
   laboratory with confirmed positive expression of NY-ESO-1 and/or, if tested, LAGE-1a.

   - Age >=18 years on the day of signing informed consent for the screening process.

   - Pending approval of Medical Monitor (or designee), participants can be enrolled in
   other experimental interventional clinical studies during the screening and
   leukapheresis stages of this study (GSK208471).

   - Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC.

   - ECOG Performance Status of 0 or 1.

   - Predicted life expectancy that is >=3 months.

   - Participant has left ventricular ejection fraction >=50 percent (%) or as per
   institution's guidelines.

   - Adequate venous access for leukapheresis.

   - In the Investigator's opinion, the participant is fit for lymphodepleting chemotherapy
   and infusion of GSK3377794.

Leukapheresis (Part 2):

   - In the Investigator's opinion, the participant is suitable for leukapheresis including
   laboratory parameters as described in the protocol.

   - Leukapheresis can be collected between the lines of therapies

   - An intermediate standard of care (SoC) line of therapy between leukapheresis (Part 2)
   and treatment (Part 3) at the time of disease progression is allowed.

Lymphodepletion/Treatment (Part 3):

   - All participants with NSCLC with WT EGFR and WT ALK/ ROS1 (Arms A and B) should have
   received and failed at least one line of programmed death protein 1/programmed death
   protein 1 ligand (PD-1/PD-L1) checkpoint blockade therapy (alone or in combination
   with systemic chemotherapy).

   - All participants with NSCLC with EGFR or ALK/ROS1 aberration (Arm C only) should have
   received and failed appropriate targeted therapy following National Comprehensive
   Cancer Network (NCCN) guidelines. These participants could have received and failed
   PD-1/PD-L1 checkpoint blockade therapy.

   - Experimental systemic regimens are allowed.

   - Histologically or cytologically diagnosed unresectable Stage IIIb or Stage IV NSCLC
   with measurable disease per RECIST version 1.1 as assessed by local site
   investigator/radiology.

   - Central nervous system (CNS) metastases with low CNS disease burden are allowed on a
   case by case basis after benefit-risk evaluation in consultation with the Sponsor
   Medical Monitor (or designee).

   - A biopsy of tumor tissue obtained following cessation of the last line of treatment
   for NSCLC but within 2 weeks prior to initiating lymphodepleting chemotherapy is
   required unless clinically unsafe to do so.

   - Contraceptive use by men or women should be consistent with local regulations
   regarding the methods of contraception for those participating in clinical studies.

   - A female participants are eligible to participate if they are not pregnant or
   breastfeeding and if she is not of childbearing potential.

   - Participant must have adequate organ function as described in the protocol.

Pembrolizumab therapy following disease progression after GSK3377794 infusion (Arm A only,
Part 4):

   - Participants who have received GSK3377794 in Arm A are eligible for therapy with
   pembrolizumab 200 milligrams flat dose once every 3 weeks if they fulfil certain
   criteria.

Exclusion Criteria:

For Screening (Part 1):

   - NSCLC with B-Raf gene (BRAF) V600E mutation, Neurotrophic Tropomyosin-Related Kinase
   (NTRK) gene fusion, and/or any other actionable genetic aberration that can be treated
   with targeted SoC (NCCN recommended) therapy.

   - Prior therapies: Arm A and B: Has received and failed >=3 lines of systemic therapy.
   Arm C: Has received >=4 lines of systemic therapy.

   - Any prior treatment with oncology cell therapy (TCR-T-cell therapy or chimeric antigen
   receptor [CAR]-T therapy); Prior gene therapy using an integrating vector.

   - Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
   compression.

   - Prior malignancy other than NSCLC, with exceptions: agreed upon consultation between
   the Investigator and Sponsor Medical Monitor (or designee).

   - Participant has an active autoimmune disease that has required systemic treatment in
   past 2 years.

   - Participant has a history of chronic or recurrent (within the last year prior to
   enrollment) severe autoimmune or active immune-mediated disease requiring steroids or
   other immunosuppressive treatments.

   - Prior allogeneic/autologous bone marrow or solid organ transplantation with some
   exceptions if occurred more than 5 years ago.

   - Uncontrolled intercurrent illness.

   - Prior or active demyelinating disease.

   - Current unstable liver or biliary disease per Investigator assessment.

   - Participant has positive viral serology as defined in protocol.

   - Participant is pregnant or breastfeeding.

   - Has known psychiatric or substance abuse disorders.

Leukapheresis (Part 2):

   - Toxicity from previous anti-cancer therapy that has not recovered to CTCAE version
   4.03 Grade <=1 prior to enrollment (except for non-clinically significant toxicities,
   e.g.,alopecia, vitiligo). Participants with existing pneumonitis because of radiation
   are not excluded; however, participants cannot be oxygen-dependent. Participants with
   Grade 2 toxicities that are deemed stable or irreversible (e.g., peripheral
   neuropathy) can be enrolled on a case-by-case basis with prior consultation and
   agreement with the Sponsor Medical Monitor (or designee).

   - Investigational treatment within 30 days or 5 half-lives (whichever is shorter) prior
   to leukapheresis.

   - Radiotherapy that involves >25% bone marrow exposure.

Lymphodepletion/ Treatment (Part 3):

   - Has received a live vaccine within 30 days prior to the first dose of study drug.

   - Major surgery <=28 days before first dose of study treatment.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Brittany Johnson
650-723-6498
Recruiting