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

Sponsor

Heat Biologics (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02439450

Collaborator

(none)

121

Enrollment

Locations

Arms

87.6

Anticipated Duration (Months)

7.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Biological: Viagenpumatucel-L Drug: Nivolumab Drug: Pembrolizumab Drug: Pemetrexed	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

121 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Apr 15, 2015

Actual Primary Completion Date :

May 3, 2021

Anticipated Study Completion Date :

Aug 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 5: Viagenpumatucel-L + Nivolumab 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 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 Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Other Names: HS-110 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. Other Names: Opdivo
Experimental: 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.	Biological: Viagenpumatucel-L Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Other Names: HS-110 Drug: 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. Other Names: Keytruda Drug: 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. Other Names: Alimta

Arm

Intervention/Treatment

Experimental: Arm 5: Viagenpumatucel-L + Nivolumab

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 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

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

Other Names:

HS-110

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.

Other Names:

Opdivo

Experimental: 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.

Biological: Viagenpumatucel-L

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

Other Names:

HS-110

Drug: 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.

Other Names:

Keytruda

Drug: 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.

Other Names:

Alimta

Outcome Measures

Primary Outcome Measures

Phase 1b: Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03. [Up to 3 years]
The number of TEAEs and 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.
Phase 2, Arm 5: Objective Response Rate (ORR) [Up to 1 year]
Defined as the number of patients achieving a best overall response of complete response (CR/iCR) or partial response (PR/iPR) by RECIST 1.1 and iRECIST. Analysis will be conducted on the ITT population.
Phase 2, Arm 6: Progression Free Survival (PFS) [Up to 3 years]
PFS will be calculated as the time between enrollment and the date of PD, as defined by RECIST 1.1 or death, whichever occurs first.

Secondary Outcome Measures

Objective Response Rate (ORR) [Up to 1 year]
Defined as the proportion of patients achieving a best overall response of complete response (CR) or partial response (PR) by RECIST 1.1. Analysis will be conducted on the Safety population.
Overall survival (OS) [Up to 3 years]
OS will be calculated as the duration of survival from the date of first HS-110 dosing into the study to the date of death from any cause or will be censored on the date the patient was last known to be alive. Also evaluated at 6 and 12 months.
Progression-Free survival (PFS) [Up to 3 years]
Calculated as the time between the date of first dose of HS-110 and the date of PD, as defined by RECIST 1.1 or death, whichever occurs first. Also evaluated at 6 and 12 months.
Duration of response (DOR) [Up to 1 year]
Calculated from the time of first confirmed response (CR or PR) until radiographic PD by RECIST 1.1
Disease control rate (DCR) [Up to 1 year]
Defined as the proportion of patients whose best overall response is PR, CR, or SD, as defined by RECIST 1.1
Durable Response Rate (DRR) [Up to 1 year]
Evaluated at 6 and 12 months. Defined as the percentage of responders with durable responses lasting at least 6 and 12 months from time of initial response by RECIST 1.1.
Frequency of treatment emergent adverse events (TEAEs) as assessed by CTCAE v4.03. [Up to 3 years]
The number of TEAEs and 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724
2	UC San Diego	La Jolla	California	United States	92093
3	BRRH Lynn Cancer Institute	Boca Raton	Florida	United States	33486
4	Memorial Cancer Institute	Pembroke Pines	Florida	United States	33028
5	Horizon Oncology Research	Lafayette	Indiana	United States	47905
6	Ashland-Bellefonte Cancer Center	Ashland	Kentucky	United States	41101
7	Baptist Health Louisville	Louisville	Kentucky	United States	40207
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	New York Oncology Hematology	Albany	New York	United States	12206
10	Winthrop Hospital	Mineola	New York	United States	11501
11	Oncology Hematology Care, Inc.	Cincinnati	Ohio	United States	45242
12	Cleveland Clinic	Cleveland	Ohio	United States	44195
13	Providence Portland Medical Center	Portland	Oregon	United States	97213
14	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
15	Rhode Island Hospital	Providence	Rhode Island	United States	02903
16	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031