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

NCT02439450 | Completed Phase 1 Results DMC

• 1 other identifier: HS110-102
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 16

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.

Conditions

Non-small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive

EXPERIMENTAL

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; Drug: Nivolumab

Arm 6: Viagenpumatucel-L + pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor

EXPERIMENTAL

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; Drug: Nivolumab

Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed

EXPERIMENTAL

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; Drug: Pembrolizumab; Drug: Pemetrexed

Interventions

Viagenpumatucel-L BIOLOGICAL

Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig

Also known as: HS-110

Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive; Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor; Arm 6: Viagenpumatucel-L + pembrolizumab; Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed

Nivolumab DRUG

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.

Also known as: Opdivo

Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive; Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor

Pembrolizumab DRUG

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.

Also known as: Keytruda

Arm 6: Viagenpumatucel-L + pembrolizumab; Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed

Pemetrexed DRUG

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.

Also known as: Alimta

Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Heat Biologics: lead

Study Sites (16)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

UC San Diego

La Jolla, California, 92093, United States

Location

BRRH Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Memorial Cancer Institute

Pembroke Pines, Florida, 33028, United States

Location

Horizon Oncology Research

Lafayette, Indiana, 47905, United States

Location

Ashland-Bellefonte Cancer Center

Ashland, Kentucky, 41101, United States

Location

Baptist Health Louisville

Louisville, Kentucky, 40207, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York Oncology Hematology

Albany, New York, 12206, United States

Location

Winthrop Hospital

Mineola, New York, 11501, United States

Location

Oncology Hematology Care, Inc.

Cincinnati, Ohio, 45242, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Nivolumab; pembrolizumab; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Vice President, Clinical Development
• Organization: NightHawk Biosciences Inc.

info@nighthawkbio.com

9197948950

Study Officials

• Daniel Morgensztern, MD

  Washington University School of Medicine in St. Louis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2015
• First Posted: May 8, 2015
• Study Start: April 15, 2015
• Primary Completion: May 3, 2021
• Study Completion: November 4, 2022
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2022-10

Locations

US (16)