Non-small Cell Lung Cancer
Conditions
Keywords
lung, cancer, gp96, vaccine, immunotherapy, Heat Biologics, Nivolumab, checkpoint inhibitor
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.
Interventions
BIOLOGICALViagenpumatucel-L
Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
DRUGNivolumab
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.
DRUGPembrolizumab
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.
DRUGPemetrexed
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.
Sponsors
Heat Biologics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03. | Up to 3 years | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 5: Viagenpumatucel-L + Nivolumab CPI Naïve Patients naïve to 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.
Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
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. | 47 |
| Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor Patients with prior 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.
Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
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. | 68 |
| Arm 6: Viagenpumatucel-L + Pembrolizumab 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.
Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
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. | 2 |
| 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.
Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig
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. | 4 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 | 0 | 0 |
| Overall Study | Death | 3 | 0 | 0 | 1 |
| Overall Study | Progressive Disease | 18 | 41 | 2 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm 5: Viagenpumatucel-L + Nivolumab CPI Naïve | Total | Arm 6: Viagenpumatucel-L + Pembrolizumab +/- Pemetrexed | Arm 6: Viagenpumatucel-L + Pembrolizumab | Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor |
|---|---|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 8.9 | 67 years STANDARD_DEVIATION 8.9 | 70 years STANDARD_DEVIATION 5.1 | 70 years STANDARD_DEVIATION 12.7 | 67 years STANDARD_DEVIATION 9.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 15 Participants | 0 Participants | 0 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 42 Participants | 102 Participants | 4 Participants | 2 Participants | 54 Participants |
| Sex: Female, Male Female | 26 Participants | 67 Participants | 3 Participants | 1 Participants | 37 Participants |
| Sex: Female, Male Male | 21 Participants | 54 Participants | 1 Participants | 1 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 39 / 47 | 60 / 68 | 2 / 2 | 3 / 4 |
| other Total, other adverse events | 47 / 47 | 66 / 68 | 2 / 2 | 4 / 4 |
| serious Total, serious adverse events | 13 / 47 | 16 / 68 | 0 / 2 | 1 / 4 |
Outcome results
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.
Time frame: Up to 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive | Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03. | 47 Participants |
| Arm 6: Viagenpumatucel-L + Pembrolizumab | Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03. | 66 Participants |
| Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor | Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03. | 2 Participants |
| Arm 6: Viagenpumatucel-L + Pembrolizumab + Pemetrexed | Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03. | 4 Participants |