A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer

Feasibility and Safety study of autologous dendritic cell immunotherapy (AGS-003-LNG) in patients with resectable non-small cell lung cancer.

Study Overview

• Status: Withdrawn
• Conditions: Non-small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Carboplatin; Biological: AGS-003-LNG; Drug: Abraxane; Drug: Alimta; Drug: Cisplatin; Drug: Taxol; Radiation: Radiation Therapy

Detailed Description

Feasibility and Safety study of autologous dendritic cell immunotherapy (AGS-003-LNG) in patients with resectable non-small cell lung cancer. Non-small cell lung cancer tumor will be resected from the patient. RNA from the tumor will be amplified and subsequently electroporated into matured, autologous dendritic cells. The dendritic cells with tumor RNA will be dosed back to the patient. Study will investigate feasibility and safety.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68118
      • Cancer Research Network of Nebraska / Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 19 years.
2. Newly diagnosed non-small cell lung cancer indicated for routine lobectomy, mediastinoscopy, wedge resection, thoracotomy or Video-assisted thoracoscopic surgery (VATS) procedures with tumor collection.
3. Stage III (T1-3, N1-2, M0) of any histology.
4. Scheduled for routine lobectomy, mediastinoscopy, wedge resection, thoracotomy or VATS procedures.
5. Signed and dated informed consent document for study participation.

After tumor collection, potential subjects must meet all the following criteria to be enrolled in study treatment:

1. Successful RNA isolation and amplification from tumor sample (as determined by Argos).
2. Karnofsky performance status (KPS) score of 80-100.
3. Life expectancy of six months or greater.
4. NSCLC of any histology.
5. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
6. Negative serum pregnancy test for female subjects with reproductive potential, and agreement of all male and female subjects of reproductive potential to use a reliable form of contraception during the study and for 12 weeks after the last dose of study drug.
7. Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study.
8. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
9. Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.

Exclusion Criteria:

1. Active autoimmune disease or condition requiring chronic immunosuppressive therapy
2. Any clinically significant condition that prohibits the initiation of standard of care.

3. Malignancies within the prior three years, except for:

   • treated in situ carcinomas or non-melanoma skin cancer.
   • adequately treated early stage breast cancer.
   • superficial bladder cancer.
   • non-metastatic prostate cancer with a normal prostate-specific antigen (PSA) level.
4. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease.

5. Clinically significant disorders or conditions including

   • cardiovascular system.
   • renal system.
   • hepatic organ system.
   • coagulation disorders.
6. Clinically significant infections, including human immunodeficiency virus (HIV), syphilis, and active hepatitis B or C.
7. Pregnant or breastfeeding.
8. Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequential, no radiation; AGS-003-LNG initiated after completion of platinum doublet chemotherapy. AGS-003-LNG induction = 1 dose administered every 3 weeks for 5 doses. Booster doses will then be administered every 12 weeks. A dose of AGS-003-LNG consists of (1.2 x 10-7 Dendritic cells.) Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin Area Under Curve (AUC) 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G).	Drug: Carboplatin; Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."; Other Names: Paraplatin; Biological: AGS-003-LNG; autologous dendritic cell immunotherapy; Drug: Abraxane; Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.; Other Names: Protein-bound paclitaxel; nab-paclitaxel; nano-particle albumin-bound paclitaxel; Drug: Alimta; By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cell; Other Names: Pemetrexed; Drug: Cisplatin; Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis; Other Names: Cisplatinum; cis-diamminedichloroplatinum(II); platamin; neoplatin; cismaplat; Drug: Taxol; Mechanism of action involves interference with the normal breakdown of microtubules during cell division.; Other Names: Paclitaxel; Radiation: Radiation Therapy; Causes DNA strand breaks.
Experimental: Concurrent, no radiation; AGS-003-LNG dosing initiated concurrently or subsequent to 3rd cycle of platinum doublet chemotherapy & radiation therapy. AGS-003-LNG induction = 1 dose administered every 3 wks for 5 doses. Booster doses will then be administered every 12 wks. A dose of AGS-003-LNG =1.2 x 10-7 Dendritic cells. Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G).	Drug: Carboplatin; Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."; Other Names: Paraplatin; Biological: AGS-003-LNG; autologous dendritic cell immunotherapy; Drug: Abraxane; Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.; Other Names: Protein-bound paclitaxel; nab-paclitaxel; nano-particle albumin-bound paclitaxel; Drug: Alimta; By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cell; Other Names: Pemetrexed; Drug: Cisplatin; Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis; Other Names: Cisplatinum; cis-diamminedichloroplatinum(II); platamin; neoplatin; cismaplat; Drug: Taxol; Mechanism of action involves interference with the normal breakdown of microtubules during cell division.; Other Names: Paclitaxel; Radiation: Radiation Therapy; Causes DNA strand breaks.
Experimental: Sequential, radiation; AGS-003-LNG initiated after completion of platinum doublet chemotherapy. AGS-003-LNG induction = 1 dose administered every 3 weeks for 5 doses. Booster doses will then be administered every 12 weeks. A dose of AGS-003-LNG consists of (1.2 x 10-7 Dendritic cells.) Platinum-doublet chemotherapy can be any of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G). Radiation therapy per PI	Drug: Carboplatin; Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."; Other Names: Paraplatin; Biological: AGS-003-LNG; autologous dendritic cell immunotherapy; Drug: Abraxane; Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.; Other Names: Protein-bound paclitaxel; nab-paclitaxel; nano-particle albumin-bound paclitaxel; Drug: Alimta; By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cell; Other Names: Pemetrexed; Drug: Cisplatin; Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis; Other Names: Cisplatinum; cis-diamminedichloroplatinum(II); platamin; neoplatin; cismaplat; Drug: Taxol; Mechanism of action involves interference with the normal breakdown of microtubules during cell division.; Other Names: Paclitaxel; Radiation: Radiation Therapy; Causes DNA strand breaks.
Experimental: Concurrent, radiation; AGS-003-LNG dosing initiated concurrently during or subsequent to the 3rd cycle (3-week cycle) of platinum doublet chemotherapy & radiation therapy. AGS-003-LNG induction = 1 dose administered every 3 wks for 5 doses. Booster doses administered every 12 wks. A dose of AGS-003-LNG =1.2 x 10-7 Dendritic cells. Platinum-doublet chemotherapy choice of the following determined by PI Carboplatin/Abraxane: ABRAXANE is 100 mg/m2 i.v. over 30 minutes on Days 1, 8, & 15 of each 21-day cycle; carboplatin AUC 6 (C&G) on Day 1 of each 21-day cycle immediately after ABRAXANE. Carboplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day cycle in combination with carboplatin AUC 6 (C&G) i.v. 30 minutes after ALIMTA. Cisplatin/Alimta ALIMTA is 500 mg/m2 i.v. on Day 1 of each 21-day with cisplatin 75 mg/m2 i.v., 30 minutes after ALIMTA. Carboplatin/Taxol TAXOL administered i.v. over 24 hrs at a dose of 135 mg/m2 followed by carboplatin, AUC 6 (C&G). Radiation therapy per PI.	Drug: Carboplatin; Carboplatin is an anticancer drug ("antineoplastic" or "cytotoxic") chemotherapy drug. Carboplatin is classified as an "alkylating agent."; Other Names: Paraplatin; Biological: AGS-003-LNG; autologous dendritic cell immunotherapy; Drug: Abraxane; Paclitaxel destroys cancer cells by preventing the normal breakdown of microtubules during cell division.; Other Names: Protein-bound paclitaxel; nab-paclitaxel; nano-particle albumin-bound paclitaxel; Drug: Alimta; By inhibiting the formation of precursor purine and pyrimidine nucleotides, pemetrexed prevents the formation of DNA and RNA, which are required for the growth and survival of both normal cells and cancer cell; Other Names: Pemetrexed; Drug: Cisplatin; Binds to and causes crosslinking of DNA, which ultimately triggers apoptosis; Other Names: Cisplatinum; cis-diamminedichloroplatinum(II); platamin; neoplatin; cismaplat; Drug: Taxol; Mechanism of action involves interference with the normal breakdown of microtubules during cell division.; Other Names: Paclitaxel; Radiation: Radiation Therapy; Causes DNA strand breaks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - Adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) V4.03	Safety of AGS-003-LNG for subjects who receive 1 or more doses of AGS-003-LNG in combination with standard platinum-doublet chemotherapy with or without radiation. Adverse events will be collected per CTCAE V4.03.	2 Years
Immunogenicity - Generation of Cluster of Differentiation-8 (CD8)+ Cluster of Differentiation (CD28)+ memory T-cells	Generation of CD8+CD28+ memory T-cells against tumor associated antigens in subject receiving 5 or more doses of AGS-003-LNG.	After 5th dose of AGS-003-LNG. Within 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - Overall survival	While the study is not powered for efficacy Overall Survival (including median and one year survival) be analyzed as an exploratory endpoints.	2 Years
Efficacy - Progression-free survival as measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.	While the study is not powered for efficacy, Progression Free Survival will be analyzed as an exploratory endpoint.	2 Years
Efficacy - Objective response rate. The number of patients with a Complete Response or Partial Response.	While the study is not powered for efficacy Objective Response Rate will be analyzed as an exploratory endpoint.	2 Years
Feasibility - Number of patients with a success in the manufacture of AGS-003-LNG.	AGS-003-LNG manufacturing success rate for non small cell lung cancer tumor RNA isolation from surgical resection.	1 Month

Collaborators and Investigators

• Sponsor: GU Research Network, LLC
• Investigators: Study Director: Luke T Nordquist, MD, Cancer Research Network of Nebraska

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: January 12, 2016
• First Submitted That Met QC Criteria: January 22, 2016
• First Posted (Estimate): January 25, 2016

Study Record Updates

• Last Update Posted (Actual): March 18, 2022
• Last Update Submitted That Met QC Criteria: March 3, 2022
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: immunotherapy; NSCLC; non-small cell lung cancer; resectable; autologous; dendritic cell
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Folic Acid Antagonists; Carboplatin; Paclitaxel; Cisplatin; Albumin-Bound Paclitaxel; Pemetrexed
• Other Study ID Numbers: AGS-003-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No