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

Heat Biologics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Nivolumab; Drug: Pemetrexed; Drug: Pembrolizumab; Biological: Viagenpumatucel-L

Study type: Interventional

Funder types: Industry

Identifiers

NCT02439450

HS110-102

Details and patient eligibility

About

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.

Full 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.

Enrollment: 121 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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121 participants in 4 patient groups

Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive

Experimental group

Description:

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.

Treatment:

Biological: Viagenpumatucel-L

Drug: Nivolumab

Arm 6: Viagenpumatucel-L + pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Biological: Viagenpumatucel-L

Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor

Experimental group

Description:

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.

Treatment:

Biological: Viagenpumatucel-L

Drug: Nivolumab

Arm 6: Viagenpumatucel-L + pembrolizumab + pemetrexed

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Biological: Viagenpumatucel-L

Drug: Pemetrexed