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

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)

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Biological: Viagenpumatucel-L; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Pemetrexed

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.

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego
  • Florida
    • Boca Raton, Florida, United States, 33486
      • BRRH Lynn Cancer Institute
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Cancer Institute
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research
  • Kentucky
    • Ashland, Kentucky, United States, 41101
      • Ashland-Bellefonte Cancer Center
    • Louisville, Kentucky, United States, 40207
      • Baptist Health Louisville
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology
    • Mineola, New York, United States, 11501
      • Winthrop Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care, Inc.
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

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

Description

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).

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: Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive; 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.	Biological: Viagenpumatucel-L; Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig; Other Names: HS-110; Drug: Nivolumab; 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.; Other Names: Opdivo
Experimental: Arm 6: Viagenpumatucel-L + pembrolizumab; 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.	Biological: Viagenpumatucel-L; Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig; Other Names: HS-110; Drug: Pembrolizumab; 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.; Other Names: Keytruda
Experimental: Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor; 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.	Biological: Viagenpumatucel-L; Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig; Other Names: HS-110; Drug: Nivolumab; 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.; Other Names: Opdivo
Experimental: Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed; 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.	Biological: Viagenpumatucel-L; Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig; Other Names: HS-110; Drug: Pembrolizumab; 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.; Other Names: Keytruda; Drug: Pemetrexed; 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.; Other Names: Alimta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Defined as the proportion of patients achieving a best overall response of complete response (CR) or partial response (PR) by RECIST 1.1. Analysis will be conducted on the Safety population.	Up to 1 year
Overall survival (OS)	OS will be calculated as the duration of survival from the date of first HS-110 dosing into the study to the date of death from any cause or will be censored on the date the patient was last known to be alive. Also evaluated at 6 and 12 months.	Up to 3 years
Progression-Free survival (PFS)	Calculated as the time between the date of first dose of HS-110 and the date of PD, as defined by RECIST 1.1 or death, whichever occurs first. Also evaluated at 6 and 12 months.	Up to 3 years
Duration of response (DOR)	Calculated from the time of first confirmed response (CR or PR) until radiographic PD by RECIST 1.1	Up to 1 year
Disease control rate (DCR)	Defined as the proportion of patients whose best overall response is PR, CR, or SD, as defined by RECIST 1.1	Up to 1 year
Durable Response Rate (DRR)	Evaluated at 6 and 12 months. Defined as the percentage of responders with durable responses lasting at least 6 and 12 months from time of initial response by RECIST 1.1.	Up to 1 year
Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03.	The number of TEAEs and 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.	Up to 3 years

Collaborators and Investigators

• Sponsor: Heat Biologics
• Investigators: Principal Investigator: Daniel Morgensztern, MD, Washington University School of Medicine in St. Louis

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2015
• Primary Completion (Actual): May 3, 2021
• Study Completion (Actual): November 4, 2022

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 6, 2015
• First Posted (Estimated): May 8, 2015

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: lung; immunotherapy; Nivolumab; cancer; vaccine; checkpoint inhibitor; 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; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Folic Acid Antagonists; Nivolumab; Pembrolizumab; Pemetrexed
• Other Study ID Numbers: HS110-102