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

Primary Purpose

Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Viagenpumatucel-L
Nivolumab
Pembrolizumab
Pemetrexed
Sponsored by
Heat Biologics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring lung, cancer, gp96, vaccine, immunotherapy, Heat Biologics, Nivolumab, checkpoint inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

  • Non-small cell lung adenocarcinoma or squamous cell carcimona
  • At least one site of measurable disease by RECIST 1.1
  • Arm 5: Received at least one prior line of therapy, but no more than three prior lines of therapy, for incurable (i.e. unresectable) or metastatic NSCLC. Up to one prior line of FDA-approved checkpoint inhibitor therapy is permitted (must have received at least 4 months of treatment) --OR--
  • Arm 6: Received front line immunotherapy (with or without chemotherapy) for incurable or metastatic NSCLC and did not progress clinically or radiographically per RECIST 1.1 at the most recent imaging assessment, and will begin maintenance immunotherapy with standard of care pembrolizumab ± pemetrexed.
  • Life expectancy ≥18 weeks
  • Arm 5: Disease progression at study entry --OR--
  • Arm 6: Documented Stable Disease, Partial Response, Complete Response (SD/PR/CR) per RECIST 1.1 after a minimum of 9 to 12 weeks of front line immunotherapy (with or without chemotherapy).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • 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
  • Willing to provide archival or fresh tumor biopsy at Screening, and fresh tumor biopsy at Week 10 when feasible.
  • Arm 5: Suitable for treatment with nivolumab per package insert --OR--
  • Arm 6: Suitable for front line maintenance treatment with pembrolizumab ± pemetrexed per the current approved package inserts.

EXCLUSION CRITERIA:

  • Arm 5: Received systemic anticancer therapy within 21 days prior to first dose of study drug
  • Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or concurrent illness, unrelated to the tumor, requiring active therapy
  • Any condition requiring concurrent systemic immunosuppressive therapy
  • Known immunodeficiency disorders, either primary or acquired
  • Known leptomeningeal disease
  • Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
  • Pregnant or breastfeeding
  • Prior participation in a clinical study of viagenpumatucel-L (HS-110)
  • Administration of a live vaccine within 30 days prior to first dose of study drug
  • Active, known or suspected autoimmune disease
  • Significant cardiovascular disease
  • Refractory to prior immunotherapy (clinical or radiographic progression after 12 weeks or less of immunotherapy).

Sites / Locations

  • University of Arizona Cancer Center
  • UC San Diego
  • BRRH Lynn Cancer Institute
  • Memorial Cancer Institute
  • Horizon Oncology Research
  • Ashland-Bellefonte Cancer Center
  • Baptist Health Louisville
  • Washington University School of Medicine
  • New York Oncology Hematology
  • Winthrop Hospital
  • Oncology Hematology Care, Inc.
  • Cleveland Clinic
  • Providence Portland Medical Center
  • University of Pennsylvania
  • Rhode Island Hospital
  • Virginia Cancer Specialists

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive

Arm 6: Viagenpumatucel-L + pembrolizumab

Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor

Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed

Arm Description

Patients naïve to checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.

HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab until confirmed disease progression or unacceptable toxicity, whichever occurs first.

Patients with prior checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.

HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab + pemetrexed every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab + pemetrexed until confirmed disease progression or unacceptable toxicity, whichever occurs first.

Outcomes

Primary Outcome Measures

Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03.
The number and percent of patients with a given TEAE will be summarized overall and by system organ class and preferred term by treatment group. The number and percent of patients with TEAEs will be tabulated by maximum severity.

Secondary Outcome Measures

Full Information

First Posted
May 4, 2015
Last Updated
September 20, 2023
Sponsor
Heat Biologics
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1. Study Identification

Unique Protocol Identification Number
NCT02439450
Brief Title
A Study of Combination Therapies With Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer
Official Title
A Phase 1b/2 Study of Viagenpumatucel-L (HS-110) in Combination With Multiple Treatment Regimens in Patients With Non-Small Cell Lung Cancer (The "DURGA" Trial)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
April 15, 2015 (Actual)
Primary Completion Date
May 3, 2021 (Actual)
Study Completion Date
November 4, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heat Biologics

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will test whether vaccination with viagenpumatucel-L combined with strategies to modulate the immune response is safe for patients with non-small cell lung adenocarcinoma or squamous cell carcinoma for incurable or metastatic disease.
Detailed Description
This study will test whether vaccination with viagenpumatucel-L combined with strategies to modulate the immune response is safe for patients with non-small cell lung adenocarcinoma or squamous cell carcinoma for incurable or metastatic disease. These methods collectively use the body's immune system to target the patient's own tumor. Immunosuppression hinders that response, and may develop in NSCLC patients in a variety of ways, such as activation of checkpoint pathways in the tumor microenvironment. Drugs that disrupt checkpoint molecule signaling like anti-PD-1 monoclonal antibodies nivolumab, may release this brake on the immune system. Tumor expression of PD-L1 plays an important role in patient response to checkpoint inhibitors; in general, clinical response to checkpoint inhibitors requires tumor expression of PD-L1 and presence of Tumor Infiltrating Lymphocytes (TIL). Combining viagenpumatucel-L with anti-PD-1 agents may enhance the vaccine's anti-tumor activity while prolonging or increasing the efficacy of the checkpoint inhibitor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
lung, cancer, gp96, vaccine, immunotherapy, Heat Biologics, Nivolumab, checkpoint inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
121 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive
Arm Type
Experimental
Arm Description
Patients naïve to checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
Arm Title
Arm 6: Viagenpumatucel-L + pembrolizumab
Arm Type
Experimental
Arm Description
HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab until confirmed disease progression or unacceptable toxicity, whichever occurs first.
Arm Title
Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor
Arm Type
Experimental
Arm Description
Patients with prior checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
Arm Title
Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed
Arm Type
Experimental
Arm Description
HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab + pemetrexed every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab + pemetrexed until confirmed disease progression or unacceptable toxicity, whichever occurs first.
Intervention Type
Biological
Intervention Name(s)
Viagenpumatucel-L
Other Intervention Name(s)
HS-110
Intervention Description
Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Other Intervention Name(s)
Alimta
Intervention Description
The recommended dose of ALIMTA (pemetrexed) when administered with carboplatin and pembrolizumab for the initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 administered as an intravenous infusion over 10 minutes prior to carboplatin on Day 1 of each 21-day cycle for 4 cycles. Pembrolizumab should be administered prior to ALIMTA when given on the same day.
Primary Outcome Measure Information:
Title
Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03.
Description
The number and percent of patients with a given TEAE will be summarized overall and by system organ class and preferred term by treatment group. The number and percent of patients with TEAEs will be tabulated by maximum severity.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: Non-small cell lung adenocarcinoma or squamous cell carcimona At least one site of measurable disease by RECIST 1.1 Arm 5: Received at least one prior line of therapy, but no more than three prior lines of therapy, for incurable (i.e. unresectable) or metastatic NSCLC. Up to one prior line of FDA-approved checkpoint inhibitor therapy is permitted (must have received at least 4 months of treatment) --OR-- Arm 6: Received front line immunotherapy (with or without chemotherapy) for incurable or metastatic NSCLC and did not progress clinically or radiographically per RECIST 1.1 at the most recent imaging assessment, and will begin maintenance immunotherapy with standard of care pembrolizumab ± pemetrexed. Life expectancy ≥18 weeks Arm 5: Disease progression at study entry --OR-- Arm 6: Documented Stable Disease, Partial Response, Complete Response (SD/PR/CR) per RECIST 1.1 after a minimum of 9 to 12 weeks of front line immunotherapy (with or without chemotherapy). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 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 Willing to provide archival or fresh tumor biopsy at Screening, and fresh tumor biopsy at Week 10 when feasible. Arm 5: Suitable for treatment with nivolumab per package insert --OR-- Arm 6: Suitable for front line maintenance treatment with pembrolizumab ± pemetrexed per the current approved package inserts. EXCLUSION CRITERIA: Arm 5: Received systemic anticancer therapy within 21 days prior to first dose of study drug Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or concurrent illness, unrelated to the tumor, requiring active therapy Any condition requiring concurrent systemic immunosuppressive therapy Known immunodeficiency disorders, either primary or acquired Known leptomeningeal disease Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome Pregnant or breastfeeding Prior participation in a clinical study of viagenpumatucel-L (HS-110) Administration of a live vaccine within 30 days prior to first dose of study drug Active, known or suspected autoimmune disease Significant cardiovascular disease Refractory to prior immunotherapy (clinical or radiographic progression after 12 weeks or less of immunotherapy).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Morgensztern, MD
Organizational Affiliation
Washington University School of Medicine in St. Louis
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
UC San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
BRRH Lynn Cancer Institute
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
Memorial Cancer Institute
City
Pembroke Pines
State/Province
Florida
ZIP/Postal Code
33028
Country
United States
Facility Name
Horizon Oncology Research
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Ashland-Bellefonte Cancer Center
City
Ashland
State/Province
Kentucky
ZIP/Postal Code
41101
Country
United States
Facility Name
Baptist Health Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
New York Oncology Hematology
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
Winthrop Hospital
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Oncology Hematology Care, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Providence Portland Medical Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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