Clinical trial NCT02439450: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: lung
cancer
gp96
vaccine
immunotherapy
Heat Biologics
Nivolumab
checkpoint inhibitor
Lead sponsor: Heat Biologics
Sponsor class: INDUSTRY
First posted: 2015-05-08
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03.
timeFrame: Up to 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Boca Raton
country: United States
facility: BRRH Lynn Cancer Institute
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute
state: Florida
city: Lafayette
country: United States
facility: Horizon Oncology Research
state: Indiana
city: Ashland
country: United States
facility: Ashland-Bellefonte Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Baptist Health Louisville
state: Kentucky
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: Mineola
country: United States
facility: Winthrop Hospital
state: New York
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc.
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
affiliation: Washington University School of Medicine in St. Louis
name: Daniel Morgensztern, MD
role: PRINCIPAL_INVESTIGATOR
References: