A Phase 2 Study of Viagenpumatucel-L (HS-110) in Patients With Non-Small Cell Lung Cancer

• Sponsor: Heat Biologics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02117024
• Collaborator: (none)
• Enrollment: 66
• Locations: 16
• Arms: 2
• Duration (Months): 45
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Determine whether viagenpumatucel-L combined with low-dose cyclophosphamide prolongs survival in patients with NSCLC who failed 2 or 3 prior lines of therapy for incurable or metastatic disease compared with chemotherapy alone.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer	Drug: Viagenpumatucel-L; Drug: Metronomic Cyclophosphamide; Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed)	Phase 2

Detailed Description

This study will test whether vaccination with viagenpumatucel-L combined with low-dose cyclophosphamide will prolong the survival of patients with non-small cell lung cancer (NSCLC) who have failed 2 or 3 prior lines of therapy for incurable or metastatic disease compared with chemotherapy alone. Patients will be randomized 2 to 1 into the viagenpumatucel-L arm and the chemotherapy alone arm, respectively.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter, Randomized Study to Evaluate the Safety and Efficacy of Viagenpumatucel-L (HS-110) in Combination With Low Dose (Metronomic) Cyclophosphamide Versus Chemotherapy Alone in Patients With Non-Small Cell Lung Adenocarcinoma After Failure of Two or Three Previous Treatment Regimens for Advanced Disease
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Dec 1, 2017
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Viagenpumatucel-L Plus Metronomic Cyclophosphamide Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks.	Drug: Viagenpumatucel-L; Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig; Other Names: HS-110 ; Drug: Metronomic Cyclophosphamide; One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks
Active Comparator: Chemotherapy Alone Patients will be treated with a physician's choice regimen until progression.	Drug: Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed); Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Up to 3 years]

   Overall survival (OS) calculated as the duration of survival from the date of randomization to the date of death from any cause, or was censored on the date the patient was last known to be alive. Survival time was calculated from the randomization date up to the date of death,or censored on the date that the patient was last known to be alive (last available visit date) utilizing Kaplan-Meier Estimate of Overall Survival Ending Events

Secondary Outcome Measures

1. Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE) [Up to 3 years]

   Evaluate the safety of the combination of viagenpumatucel-L and low-dose cyclophosphamide by frequency of Treatment-Emergent Adverse Events

2. Disease Control Rate (DCR) [Up to 3 years]

   Evaluate overall immune-related DCR (irDCR) and also DCR by Response Evaluation Criteria in Solid Tumors (RECIST) (complete response, partial response, and stable disease)

3. 6-Month Disease Control Rate (6mDCR) [6 months]

   Evaluate 6-month immune-related DCR (6m-irDCR) and also 6mDCR by RECIST (complete response, partial response, and stable disease at 6 months following randomization)

4. Overall Response Rate (ORR) [Up to 3 years]

   Evaluate immune-related ORR (irORR) and also ORR by RECIST (complete response and partial response)

5. Progression-Free Survival (PFS) [Up to 3 years]

   Evaluate immune-related PFS (irPFS) and PFS by RECIST (Response Evaluation Criteria for Solid Tumors)

6. Time to Progression (TTP) [Up to 3 years]

   Evaluate immune-related TTP (irTTP) and also TTP (Time to Progression) by RECIST

7. Survival at 6 Months [6 months]

   Evaluate the proportion of patients who are alive at 6 months following randomization

8. Survival at 12 Months [12 months]

   Evaluate the proportion of patients who are alive at 12 months following randomization

9. Immune Response [Up to 3 years]

   Characterize the peripheral blood immunologic response via intracellular cytokine staining (ICS) by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) on cluster of differentiation 8 positive (CD8+) cells following vaccination

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Non-small cell lung adenocarcinoma

• At least 2 and no more than 3 prior lines of therapy for incurable or metastatic NSCLC

• Suitable for conventional single agent chemotherapy

• Disease progression at study entry

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1; PS=2 patients may be considered

• 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

Exclusion Criteria:

• Received systemic anticancer therapy or radiation therapy within the previous 14 days

• Received more than 3 lines of prior conventional therapy for advanced disease

• Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or intercurrent illness, unrelated to the tumor, requiring active therapy

• Any condition requiring concurrent systemic immunosuppressive therapy

• Known immunodeficiency disorders

• Known leptomeningeal disease

• Other active malignancies

• Prior treatment with a cancer vaccine for this indication

• Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Rogers	Arkansas	United States	72758
2	University of California San Diego	La Jolla	California	United States	92093
3	University of California at Los Angeles	Los Angeles	California	United States	90029
4	University of California Davis	Sacramento	California	United States	95817
5	Georgia Regents University	Augusta	Georgia	United States	30912
6	University of Maryland Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
7	University of Massachusetts	Worcester	Massachusetts	United States	01655
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
9	SUNY Syracuse	Syracuse	New York	United States	13210
10	Gabrail Cancer Center	Canton	Ohio	United States	44718
11	Providence Portland Medical Center- Providence Lung Cancer Clinic	Portland	Oregon	United States	97213
12	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
13	Texas Oncology PA Texas Cancer Center	Abilene	Texas	United States	79606
14	Mary Crowley Cancer Center	Dallas	Texas	United States	75201
15	Cancer Care Northwest	Spokane	Washington	United States	99216
16	Aurora Research Institute	Green Bay	Wisconsin	United States	54311

Sponsors and Collaborators

• Heat Biologics

Investigators

• Principal Investigator: Roger Cohen, MD, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 29, 2014

More Information

Publications

None provided.

• Responsible Party: Heat Biologics
• ClinicalTrials.gov Identifier: NCT02117024
• Other Study ID Numbers: HS110-201
• First Posted: Apr 17, 2014
• Last Update Posted: Feb 5, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Heat Biologics: lung; cancer; gp96; vaccine; immunotherapy; Heat Biologics; cyclophosphamide; vinorelbine; erlotinib; gemcitabine; paclitaxel; docetaxel; pemetrexed
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Gemcitabine; Paclitaxel; Vinorelbine; Docetaxel; Cyclophosphamide; Pemetrexed; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Period Title: Overall Study
STARTED	45	21
COMPLETED	1	1
NOT COMPLETED	44	20

Baseline Characteristics

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone	Total
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed	Total of all reporting groups
Overall Participants	45	21	66
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	21 46.7%	12 57.1%	33 50%
>=65 years	24 53.3%	9 42.9%	33 50%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (8.9)	63.0 (10.5)	64.8 (9.4)
Sex: Female, Male (Count of Participants)
Female	27 60%	10 47.6%	37 56.1%
Male	18 40%	11 52.4%	29 43.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.2%	0 0%	1 1.5%
Not Hispanic or Latino	44 97.8%	21 100%	65 98.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 4.8%	1 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 9.5%	2 3%
White	44 97.8%	18 85.7%	62 93.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.2%	0 0%	1 1.5%
Region of Enrollment (Count of Participants)
United States	38 84.4%	18 85.7%	56 84.8%
Australia	7 15.6%	3 14.3%	10 15.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) calculated as the duration of survival from the date of randomization to the date of death from any cause, or was censored on the date the patient was last known to be alive. Survival time was calculated from the randomization date up to the date of death,or censored on the date that the patient was last known to be alive (last available visit date) utilizing Kaplan-Meier Estimate of Overall Survival Ending Events
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	45	21
Median (95% Confidence Interval) [Days]	176	372

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Viagenpumatucel-L Plus Metronomic Cyclophosphamide, Chemotherapy Alone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Viagenpumatucel-L Plus Metronomic Cyclophosphamide, Chemotherapy Alone
	Comments	With only 50% of enrollment complete prior to study termination by sponsor, insufficient sample size exists to fully complete efficacy analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	Other
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE)
Description	Evaluate the safety of the combination of viagenpumatucel-L and low-dose cyclophosphamide by frequency of Treatment-Emergent Adverse Events
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Safety was defined as the number of adverse events (AE)/serious adverse events (SAE) in patients receiving viagenpumatucel-L and low-dose Cyclophosphamide (CY).

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	43	20
At least one TEAE	41 91.1%	20 95.2%
At least one severe TEAE	25 55.6%	11 52.4%
At least one treatment-related TEAE	32 71.1%	15 71.4%
At least one SAE	17 37.8%	8 38.1%
Fatal TEAE	7 15.6%	0 0%
At least one TEAE Leading to Tx Discontinuation	7 15.6%	2 9.5%
At least one TEAE Leading to a Dose Reduction	0 0%	2 9.5%

3. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Evaluate overall immune-related DCR (irDCR) and also DCR by Response Evaluation Criteria in Solid Tumors (RECIST) (complete response, partial response, and stable disease)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Data were not collected for Outcome Measure 3 due to study termination (50% enrollment) by the Sponsor on 01 September 2015 due to changing treatment landscape (PD-1 approvals), and a subsequent change in development focus to Immuno-Oncology (IO) combinations. See NCT02439450.

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	0	0

4. Secondary Outcome

Title	6-Month Disease Control Rate (6mDCR)
Description	Evaluate 6-month immune-related DCR (6m-irDCR) and also 6mDCR by RECIST (complete response, partial response, and stable disease at 6 months following randomization)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Data were not collected for Outcome Measure 4 due to study termination (50% enrollment) by the Sponsor on 01 September 2015 due to changing treatment landscape (PD-1 approvals), and a subsequent change in development focus to Immuno-Oncology (IO) combinations. See NCT02439450.

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	0	0

5. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	Evaluate immune-related ORR (irORR) and also ORR by RECIST (complete response and partial response)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Data were not collected for Outcome Measure 5 due to study termination (50% enrollment) by the Sponsor on 01 September 2015 due to changing treatment landscape (PD-1 approvals), and a subsequent change in development focus to Immuno-Oncology (IO) combinations. See NCT02439450.

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	0	0

6. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Evaluate immune-related PFS (irPFS) and PFS by RECIST (Response Evaluation Criteria for Solid Tumors)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Calculated from randomization date to earliest date of first 'Progressive Disease' response (Immune-Related / RECIST Response Criteria) or date of death, and censored on the date of the last available post-baseline tumor assessment.

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	45	21
immune-related PFS (irPFS)	76.0	190.0
Progression Free Survival (PFS)	70.0	190.0

7. Secondary Outcome

Title	Time to Progression (TTP)
Description	Evaluate immune-related TTP (irTTP) and also TTP (Time to Progression) by RECIST
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Time to immune-related progression was calculated from the randomization date up to the date of the first 'Progressive Disease' response (Immune-Related Response Criteria) Time to progression was calculated from the randomization date up to the date of the first 'Progressive Disease' response (RECIST Response Criteria).

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	45	21
immune-related TTP (irTTP)	67.0	71.0
Time to Progression (TTP)	67.5	73.5

8. Secondary Outcome

Title	Survival at 6 Months
Description	Evaluate the proportion of patients who are alive at 6 months following randomization
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	45	21
Count of Participants [Participants]	21 46.7%	17 81%

9. Secondary Outcome

Title	Survival at 12 Months
Description	Evaluate the proportion of patients who are alive at 12 months following randomization
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	45	21
Count of Participants [Participants]	8 17.8%	11 52.4%

10. Secondary Outcome

Title	Immune Response
Description	Characterize the peripheral blood immunologic response via intracellular cytokine staining (ICS) by flow cytometry and/or enzyme-linked immunosorbent spot (ELISPOT) on cluster of differentiation 8 positive (CD8+) cells following vaccination
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Data were not collected for Outcome Measure 10 due to study termination (50% enrollment) by the Sponsor on 01 September 2015 due to changing treatment landscape (PD-1 approvals), and a subsequent change in development focus to Immuno-Oncology (IO) combinations. See NCT02439450.

Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide	Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks	Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
Measure Participants	0	0

Adverse Events

Time Frame	1 year and 5 months
Arm/Group Title	Viagenpumatucel-L Plus Metronomic Cyclophosphamide		Chemotherapy Alone
Arm/Group Description	Viagenpumatucel-L (HS-110) given as 1*10^7 cells for 12 weekly injections followed by injections every 9 weeks for up to 12 months or until discontinuation from study treatment, whichever occurs first, plus metronomic cyclophosphamide therapy for the first 12 weeks. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Metronomic Cyclophosphamide: One 50mg tablet administered orally daily for 7 days on alternating weeks for a total of 6 weeks of therapy over 12 weeks		Patients will be treated with a physician's choice regimen until progression. Physician's Choice Regimen (Vinorelbine, Erlotinib, Gemcitabine, Paclitaxel, Docetaxel, Pemetrexed): Physician will select one of the following to be given in nominal 21 day cycles with dose and route according to investigator's standard practice: Vinorelbine Erlotinib Gemcitabine Paclitaxel Docetaxel Pemetrexed
All Cause Mortality
	Viagenpumatucel-L Plus Metronomic Cyclophosphamide		Chemotherapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/43 (16.3%)		0/20 (0%)
Serious Adverse Events
	Viagenpumatucel-L Plus Metronomic Cyclophosphamide		Chemotherapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/43 (39.5%)		8/20 (40%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/43 (0%)	0	2/20 (10%)	2
Lymphadenopathy	1/43 (2.3%)	1	0/20 (0%)	0
Cardiac disorders
Cardiac Arrest	1/43 (2.3%)	1	0/20 (0%)	0
Endocrine disorders
Inappropriate Antidiuretic Hormone Secretion	0/43 (0%)	0	1/20 (5%)	1
Gastrointestinal disorders
Abdominal Pain	1/43 (2.3%)	1	0/20 (0%)	0
Ileus	1/43 (2.3%)	1	0/20 (0%)	0
Oesophagitis Ulcerative	0/43 (0%)	0	1/20 (5%)	1
Vomiting	0/43 (0%)	0	2/20 (10%)	2
General disorders
Disease Progression	2/43 (4.7%)	2	0/20 (0%)	0
Pain	1/43 (2.3%)	1	0/20 (0%)	0
Infections and infestations
Oral Candidiasis	1/43 (2.3%)	1	0/20 (0%)	0
Pneumonia	1/43 (2.3%)	1	1/20 (5%)	1
Injury, poisoning and procedural complications
Cervical Vertebral Fracture	1/43 (2.3%)	1	1/20 (5%)	1
Humerus Fracture	1/43 (2.3%)	1	1/20 (5%)	1
Metabolism and nutrition disorders
Dehydration	1/43 (2.3%)	1	0/20 (0%)	0
Hyponatraemia	1/43 (2.3%)	1	0/20 (0%)	0
Musculoskeletal and connective tissue disorders
Back Pain	1/43 (2.3%)	1	0/20 (0%)	0
Neck Pain	0/43 (0%)	0	1/20 (5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Pleural Effusion	1/43 (2.3%)	1	0/20 (0%)	0
Nervous system disorders
Cerebrovascular Accident	0/43 (0%)	0	1/20 (5%)	1
Psychiatric disorders
Mental Status Changes	1/43 (2.3%)	1	0/20 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure	1/43 (2.3%)	1	0/20 (0%)	0
Chronic Obstructive Pulmonary Disease	1/43 (2.3%)	1	0/20 (0%)	0
Dyspnoea	1/43 (2.3%)	1	1/20 (5%)	1
Respiratory Failure	1/43 (2.3%)	1	0/20 (0%)	0
Pulmonary Embolism	2/43 (4.7%)	2	0/20 (0%)	0
Vascular disorders
Deep Vein Thrombosis	0/43 (0%)	0	1/20 (5%)	1
Superior Vena Cava Syndrome	0/43 (0%)	0	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Viagenpumatucel-L Plus Metronomic Cyclophosphamide		Chemotherapy Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/43 (44.2%)		9/20 (45%)
Respiratory, thoracic and mediastinal disorders
Cough	5/43 (11.6%)	5	4/20 (20%)	5
Dyspnoea	11/43 (25.6%)	15	7/20 (35%)	8
Nasal Congestion	3/43 (7%)	3	0/20 (0%)	0
Interstitial Lung Disease	0/43 (0%)	0	1/20 (5%)	1
Oropharyngeal Pain	0/43 (0%)	0	1/20 (5%)	1
Pleuritic Pain	0/43 (0%)	0	1/20 (5%)	1
Rhinorrhea	1/43 (2.3%)	1	1/20 (5%)	1
Upper Respiratory Tract Congestion	1/43 (2.3%)	1	1/20 (5%)	1
Wheezing	0/43 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
Alopecia	2/43 (4.7%)	2	2/20 (10%)	2
Blister	0/43 (0%)	0	1/20 (5%)	2
Eczema	0/43 (0%)	0	1/20 (5%)	1
Night Sweats	1/43 (2.3%)	1	2/20 (10%)	2
Onychomadesis	0/43 (0%)	0	1/20 (5%)	1
Pruritis	2/43 (4.7%)	3	1/20 (5%)	1
Rash	1/43 (2.3%)	1	1/20 (5%)	2
Deep Vein Thrombosis	1/43 (2.3%)	1	1/20 (5%)	1
Hot Flush	1/43 (2.3%)	1	2/20 (10%)	2
Superior Vena Cava Syndrome	0/43 (0%)	0	1/20 (5%)	1

Limitations/Caveats

Study was discontinued prematurely (50% enrollment) by the Sponsor on 01 September 2015 due to changing treatment landscape (PD-1 approvals), and a subsequent change in development focus to IO combinations. See NCT02439450.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.