A Phase 2 Study of Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer

A Phase 2, Multicenter, Randomized Study to Evaluate the Safety and Efficacy of Viagenpumatucel-L (HS-110) in Combination With Low Dose (Metronomic) Cyclophosphamide Versus Chemotherapy Alone in Patients With Non-Small Cell Lung Adenocarcinoma After Failure of Two or Three Previous Treatment Regimens for Advanced Disease

Determine whether viagenpumatucel-L combined with low-dose cyclophosphamide prolongs survival in patients with NSCLC who failed 2 or 3 prior lines of therapy for incurable or metastatic disease compared with chemotherapy alone.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Viagenpumatucel-L; Drug: Metronomic Cyclophosphamide; Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed)

Detailed Description

This study will test whether vaccination with viagenpumatucel-L combined with low-dose cyclophosphamide will prolong the survival of patients with non-small cell lung cancer (NSCLC) who have failed 2 or 3 prior lines of therapy for incurable or metastatic disease compared with chemotherapy alone. Patients will be randomized 2 to 1 into the viagenpumatucel-L arm and the chemotherapy alone arm, respectively.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Rogers, Arkansas, United States, 72758
      • Highlands Oncology Group
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Los Angeles, California, United States, 90029
      • University of California at Los Angeles
    • Sacramento, California, United States, 95817
      • University of California Davis
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Georgia Regents University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Syracuse
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center- Providence Lung Cancer Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Abilene, Texas, United States, 79606
      • Texas Oncology PA Texas Cancer Center
    • Dallas, Texas, United States, 75201
      • Mary Crowley Cancer Center
  • Washington
    • Spokane, Washington, United States, 99216
      • Cancer Care Northwest
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54311
      • Aurora Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Non-small cell lung adenocarcinoma
• At least 2 and no more than 3 prior lines of therapy for incurable or metastatic NSCLC
• Suitable for conventional single agent chemotherapy
• Disease progression at study entry
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1; PS=2 patients may be considered
• Central nervous system (CNS) metastases may be permitted but must be treated and neurologically stable
• Adequate laboratory parameters
• Willing and able to comply with the protocol and sign informed consent
• Female patients who are of childbearing potential and fertile male patients must agree to use an effective form of contraception throughout study participation

Exclusion Criteria:

• Received systemic anticancer therapy or radiation therapy within the previous 14 days
• Received more than 3 lines of prior conventional therapy for advanced disease
• Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or intercurrent illness, unrelated to the tumor, requiring active therapy
• Any condition requiring concurrent systemic immunosuppressive therapy
• Known immunodeficiency disorders
• Known leptomeningeal disease
• Other active malignancies
• Prior treatment with a cancer vaccine for this indication
• Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Viagenpumatucel-L Plus Metronomic Cyclophosphamide; Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks.	Drug: Viagenpumatucel-L; Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig; Other Names: HS-110; Drug: Metronomic Cyclophosphamide; One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks
Active Comparator: Chemotherapy Alone; Patients will be treated with a physician's choice regimen until progression.	Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed); Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine; Erlotinib; Gemcitabine; Paclitaxel; Docetaxel; Pemetrexed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS) calculated as the duration of survival from the date of randomization to the date of death from any cause, or was censored on the date the patient was last known to be alive. Survival time was calculated from the randomization date up to the date of death,or censored on the date that the patient was last known to be alive (last available visit date) utilizing Kaplan-Meier Estimate of Overall Survival Ending Events	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE)	Evaluate the safety of the combination of viagenpumatucel-L and low-dose cyclophosphamide by frequency of Treatment-Emergent Adverse Events	Up to 3 years
Disease Control Rate (DCR)	Evaluate overall immune-related DCR (irDCR) and also DCR by Response Evaluation Criteria in Solid Tumors (RECIST) (complete response, partial response, and stable disease)	Up to 3 years
6-Month Disease Control Rate (6mDCR)	Evaluate 6-month immune-related DCR (6m-irDCR) and also 6mDCR by RECIST (complete response, partial response, and stable disease at 6 months following randomization)	6 months
Overall Response Rate (ORR)	Evaluate immune-related ORR (irORR) and also ORR by RECIST (complete response and partial response)	Up to 3 years
Progression-Free Survival (PFS)	Evaluate immune-related PFS (irPFS) and PFS by RECIST (Response Evaluation Criteria for Solid Tumors)	Up to 3 years
Time to Progression (TTP)	Evaluate immune-related TTP (irTTP) and also TTP (Time to Progression) by RECIST	Up to 3 years
Survival at 6 Months	Evaluate the proportion of patients who are alive at 6 months following randomization	6 months
Survival at 12 Months	Evaluate the proportion of patients who are alive at 12 months following randomization	12 months
Immune Response	Characterize the peripheral blood immunologic response via intracellular cytokine staining (ICS) by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) on cluster of differentiation 8 positive (CD8+) cells following vaccination	Up to 3 years

Collaborators and Investigators

• Sponsor: Heat Biologics
• Investigators: Principal Investigator: Roger Cohen, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: April 15, 2014
• First Submitted That Met QC Criteria: April 16, 2014
• First Posted (Estimate): April 17, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: January 24, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: lung; immunotherapy; cancer; vaccine; paclitaxel; erlotinib; cyclophosphamide; gemcitabine; docetaxel; pemetrexed; vinorelbine; gp96; Heat Biologics
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Folic Acid Antagonists; Gemcitabine; Docetaxel; Cyclophosphamide; Paclitaxel; Erlotinib Hydrochloride; Vinorelbine; Pemetrexed
• Other Study ID Numbers: HS110-201