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

• ClinicalTrials.gov Identifier: NCT02117024
• Recruitment Status: Terminated
• First Posted: April 17, 2014
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Sponsor: Heat Biologics
• Information provided by (Responsible Party): Heat Biologics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: Viagenpumatucel-L; Drug: Metronomic Cyclophosphamide; Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed)	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: July 2014
• Actual Primary Completion Date: December 2017
• Actual Study Completion Date: April 2018

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Up to 3 years ]

   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

Secondary Outcome Measures :

1. Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE) [ Time Frame: Up to 3 years ]
   Evaluate the safety of the combination of viagenpumatucel-L and low-dose cyclophosphamide by frequency of Treatment-Emergent Adverse Events
2. Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
   Evaluate overall immune-related DCR (irDCR) and also DCR by Response Evaluation Criteria in Solid Tumors (RECIST) (complete response, partial response, and stable disease)
3. 6-Month Disease Control Rate (6mDCR) [ Time Frame: 6 months ]
   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)
4. Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
   Evaluate immune-related ORR (irORR) and also ORR by RECIST (complete response and partial response)
5. Progression-Free Survival (PFS) [ Time Frame: Up to 3 years ]
   Evaluate immune-related PFS (irPFS) and PFS by RECIST (Response Evaluation Criteria for Solid Tumors)
6. Time to Progression (TTP) [ Time Frame: Up to 3 years ]
   Evaluate immune-related TTP (irTTP) and also TTP (Time to Progression) by RECIST
7. Survival at 6 Months [ Time Frame: 6 months ]
   Evaluate the proportion of patients who are alive at 6 months following randomization
8. Survival at 12 Months [ Time Frame: 12 months ]
   Evaluate the proportion of patients who are alive at 12 months following randomization
9. Immune Response [ Time Frame: Up to 3 years ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arkansas

Highlands Oncology Group

Rogers, Arkansas, United States, 72758

United States, California

University of California San Diego

La Jolla, California, United States, 92093

University of California at Los Angeles

Los Angeles, California, United States, 90029

University of California Davis

Sacramento, California, United States, 95817

United States, Georgia

Georgia Regents University

Augusta, Georgia, United States, 30912

United States, Maryland

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States, 21201

United States, Massachusetts

University of Massachusetts

Worcester, Massachusetts, United States, 01655

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

SUNY Syracuse

Syracuse, New York, United States, 13210

United States, Ohio

Gabrail Cancer Center

Canton, Ohio, United States, 44718

United States, Oregon

Providence Portland Medical Center- Providence Lung Cancer Clinic

Portland, Oregon, United States, 97213

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Texas Oncology PA Texas Cancer Center

Abilene, Texas, United States, 79606

Mary Crowley Cancer Center

Dallas, Texas, United States, 75201

United States, Washington

Cancer Care Northwest

Spokane, Washington, United States, 99216

United States, Wisconsin

Aurora Research Institute

Green Bay, Wisconsin, United States, 54311

Sponsors and Collaborators

Heat Biologics

Investigators

• Principal Investigator: Roger Cohen, MD; University of Pennsylvania

  Study Documents (Full-Text)

Documents provided by Heat Biologics:

Study Protocol and Statistical Analysis Plan  [PDF] October 29, 2014

More Information

• Responsible Party: Heat Biologics
• ClinicalTrials.gov Identifier: NCT02117024
• Other Study ID Numbers: HS110-201
• First Posted: April 17, 2014
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Last Verified: January 2020

Keywords provided by Heat Biologics:

lung; cancer; gp96; vaccine; immunotherapy; Heat Biologics; cyclophosphamide; vinorelbine; erlotinib; gemcitabine; paclitaxel; docetaxel; pemetrexed

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Paclitaxel; Vinorelbine; Docetaxel; Cyclophosphamide; Gemcitabine; Pemetrexed; Erlotinib Hydrochloride; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists