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

Non-small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02439450
• Other study ID #: HS110-102
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 15, 2015
• Est. completion date: November 4, 2022

Study information

• Verified date: October 2022
• Source: Heat Biologics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: November 4, 2022
• Est. primary completion date: May 3, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• Viagenpumatucel-L
Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	New York Oncology Hematology	Albany	New York
United States	Ashland-Bellefonte Cancer Center	Ashland	Kentucky
United States	BRRH Lynn Cancer Institute	Boca Raton	Florida
United States	Oncology Hematology Care, Inc.	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	UC San Diego	La Jolla	California
United States	Horizon Oncology Research	Lafayette	Indiana
United States	Baptist Health Louisville	Louisville	Kentucky
United States	Winthrop Hospital	Mineola	New York
United States	Memorial Cancer Institute	Pembroke Pines	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Heat Biologics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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