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

• ClinicalTrials.gov Identifier: NCT02439450
• Recruitment Status: Completed
• First Posted: May 8, 2015
• Last Update Posted: November 14, 2022
• Sponsor: Heat Biologics
• Information provided by (Responsible Party): Heat Biologics

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.

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Biological: Viagenpumatucel-L; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Pemetrexed	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 121 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: April 15, 2015
• Actual Primary Completion Date: May 3, 2021
• Actual Study Completion Date: November 4, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm 5: Viagenpumatucel-L + Nivolumab; 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 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Alimta

Outcome Measures

Primary Outcome Measures :

1. Phase 1b: Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03. [ Time Frame: Up to 3 years ]
   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.
2. Phase 2, Arm 5: Objective Response Rate (ORR) [ Time Frame: Up to 1 year ]
   Defined as the number of patients achieving a best overall response of complete response (CR/iCR) or partial response (PR/iPR) by RECIST 1.1 and iRECIST. Analysis will be conducted on the ITT population.
3. Phase 2, Arm 6: Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
   PFS will be calculated as the time between enrollment and the date of PD, as defined by RECIST 1.1 or death, whichever occurs first.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Up to 1 year ]
   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.
2. Overall survival (OS) [ Time Frame: Up to 3 years ]
   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.
3. Progression-Free survival (PFS) [ Time Frame: Up to 3 years ]
   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.
4. Duration of response (DOR) [ Time Frame: Up to 1 year ]
   Calculated from the time of first confirmed response (CR or PR) until radiographic PD by RECIST 1.1
5. Disease control rate (DCR) [ Time Frame: Up to 1 year ]
   Defined as the proportion of patients whose best overall response is PR, CR, or SD, as defined by RECIST 1.1
6. Durable Response Rate (DRR) [ Time Frame: Up to 1 year ]
   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.
7. Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03. [ Time Frame: Up to 3 years ]
   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.

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 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).

Contacts and Locations

Locations

United States, Arizona

University of Arizona Cancer Center

Tucson, Arizona, United States, 85724

United States, California

UC San Diego

La Jolla, California, United States, 92093

United States, Florida

BRRH Lynn Cancer Institute

Boca Raton, Florida, United States, 33486

Memorial Cancer Institute

Pembroke Pines, Florida, United States, 33028

United States, Indiana

Horizon Oncology Research

Lafayette, Indiana, United States, 47905

United States, Kentucky

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, United States, 41101

Baptist Health Louisville

Louisville, Kentucky, United States, 40207

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, New York

New York Oncology Hematology

Albany, New York, United States, 12206

Winthrop Hospital

Mineola, New York, United States, 11501

United States, Ohio

Oncology Hematology Care, Inc.

Cincinnati, Ohio, United States, 45242

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Oregon

Providence Portland Medical Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Sponsors and Collaborators

Heat Biologics

Investigators

• Principal Investigator: Daniel Morgensztern, MD; Washington University School of Medicine in St. Louis

More Information

• Responsible Party: Heat Biologics
• ClinicalTrials.gov Identifier: NCT02439450
• Other Study ID Numbers: HS110-102
• First Posted: May 8, 2015
• Last Update Posted: November 14, 2022
• Last Verified: October 2022

Keywords provided by Heat Biologics:

lung; cancer; gp96; vaccine; immunotherapy; Heat Biologics; Nivolumab; checkpoint inhibitor

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; Pembrolizumab; Nivolumab; Pemetrexed; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors