A fine needle aspiration is not acceptable. Additional tissue collect ion and preparation procedures are provided in a separate Biopsy Manual . Boosting Visits and Assessments (Week 14 to EOT ) Following the 1 3-week prim ing period, HS-110 injections will be administered for boosting every 3 weeks (± 3 days) in combination with SOC pembrolizumab ± pemetrexed until confirmed disease progression. During this time, r adiological assessments will continue every 9 weeks until confirmation of iCPD per iRECIST. Concomitant medications and AE/SAEs will also be recorded . 10.6. Arm 6: End of Treatment The following procedures should be completed approximately 3 to 4 weeks following last dose of HS-110, including patients who discontinue dosing prematurely. • Full PE (including height and weight) • Vital signs (blood pressure , heart rate , respiratory rate, and temperature) • Blood draw for IR (Section 14.2) • Blood draw for hematology and serum chemistry (Section 13.2) • Record AEs experienced by the patient • Record concomitant medications 10.7. Arm 6: Survival Follow -Up (Progressive Disease until Death) The survival follow -up period refers to the tim e between the confirmation of PD and patient death. Patients will be followed for OS. Survival status and subsequent anti -cancer therapy will be collected approximately every 3 months in a clinic visit or by telephone if the patient is no longer attending clinic visits at the investigative site. 10.8. Schedule of Activities (SOA) Table 2 outline s the clinical assessments and treatments by week for Arm 5 receiving HS-110 in combination with nivolumab and Table 3 outlines the clinical assessments and treatments by week for Arm 6 receiving HS-110 in combination with pembrolizumab ± pemetrexed . Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 51 of 95 Table 2: Schedule of Activities (Arm 5: HS-110+ Nivolumab) 1 EOT should be completed approximately 3 to 4 weeks following last dose of HS-110, including for patients who discontinue dosing prematurely. 2 Baseline procedures may be combined with Week 1 visit, as long as they are performed prior to dosing. 3 Full phys ical exam will be performed at S creening and EOT and includes obtaining the patient’s height and weight , and an assessment of the following body systems: HEENT, Pulmonary, Cardiovascular, Musculoskeletal, Abdominal/Gastrointestinal, Lymphatic, Neurolog ical, Dermatologic, and Genito -urinary systems . Abbreviated physical exams will be conducted at Weeks 2, 3, 4, 5, 7, 11, and 15 and are limited to vital signs and symptoms unless otherwise clinically indicated. 4 Blood draw for hematology requires 5 mL and serum chemistry requires 5 mL ; hematology assessments include white blood cell (WBC) with differential, platelet count, hemoglobin, red blood cell (RBC) count and absolute neutrophils; chemistry includes serum assessment of sodium, calcium, total protein , albumin, creatinine, blood urea nitrogen (BUN), total bilirubin, alkaline phosphatase, AST, ALT, potassium, chloride, sodium bicarbonate, lactate dehydrogenase, and glucose . 5 Repeat assessment at Baseline only if Screening Visit was performed > 2 weeks prior to dosing . 6 Blood draw for Tropo nin I or T requires 5 mL (performed at Screening and Weeks 1 through 4). 7 Urine or serum pregnancy test. Blood draw for serum pregnancy test for women of childbearing potential requires 1 mL (performed at Screening and Baseline prior to dosing). 8 Blood draw for TMB requires 20 ml of blood at Week 1 prior to dosing. 9 Cohort B Patients who enrolled prior to Amendment 5 and did not have a week 1 TMB sample drawn should have this sample collec ted at the next feasible vis it.. 10 Blood draw for IR requires 50 mL of blood (performed at Screening and at Weeks 7, 13 and EOT). 11 Tissue biopsy sample collection may be archival or fresh at screening , and fresh tissue collected at Week 10 when feasible. Activity Screening Week EOT1 Post-HS- 110 FU Survival FU D-28 to D -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Study Day Baseline2 D-7 to D1 8 ±2 15 ±3 22 ±3 29 ±3 36 ±3 43 ±3 50 ±3 57 ±3 64 ±3 71 ±3 78 ±3 85 ±3 92 ±3 99 ±3 106 ±3 113 ±3 120 ±3 +21 to 28 Q8 weeks Q3 months Informed Consent X Medical History X X Demographics X ECOG PS X X PE with vital s X3 X X X X X X X X3 Hematology4 and serum chemistry4 X X5 X X X X X X Troponin I or T6 X X X X X Pregnancy Test7 X X5 Tumor Mutation Burden Lab8 X9 Immunologic Response Lab10 X X X X Tissue Sample Collection11 X X Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 52 of 95 12 Tumor assessment will be evaluated by RECIST 1.1 and iRECIST 13 Only subsequent anti -cancer therapy will be recorded 14 30 minute observation after first dose only 15 Nivolumab will be administered every 2 weeks while receiving HS -110 treatment 16 Nivolumab dosing schedule during Post -HS-110 Follow Up determined per Investigator discretion 17 AEs/SAEs to be recorded up to 4 weeks after the last administration of HS-110, and followed until resolution (unless not res olvable due to underlying disease) 18 Only AEs deemed related to study drug will be recorded Activity Screening Week EOT1 Post-HS- 110 FU Survival FU D-28 to D -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Study Day Baseline2 D-7 to D1 8 ±2 15 ±3 22 ±3 29 ±3 36 ±3 43 ±3 50 ±3 57 ±3 64 ±3 71 ±3 78 ±3 85 ±3 92 ±3 99 ±3 106 ±3 113 ±3 120 ±3 +21 to 28 Q8 weeks Q3 months Tumor Assessment by CT or MRI12 X X X Q8 weeks from wk 18 ECG X X ECHO or MUGA with LVEF X Verify eligibility criteria X X X Prior and Concomitant Medications X X X X X X X X X X X X X X X X X X X X X X11 X13 HS-110 Administration X14 X X X X X X X X X X X X X X X X X SOC Nivolumab administration15 X X X X X X X X X Q2 or Q4 weeks16 Record AEs/SAEs17 X X X X X X X X X X X X X X X X X X X X18 Survival Status X Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 53 of 95 Table 3: Schedule of Activities (Arm 6: HS-110 + Pembrolizumab +/- Pemetrexed ) 19 EOT should be completed approximately 3 to 4 weeks following last dose of HS-110, including premature/early termination of HS -110 treatment . 20 Baseline procedur es may be combined with Week 1 visit, as long as they are performed prior to dosing. 21 Full phys ical exam will be performed at S creening and EOT and includes obtaining the patient’s height and weight , and an assessment of the following body systems: HEENT, Pulmonary, Cardiovascular, Musculoskeletal, Abdominal/Gastrointestinal, Lymphatic, Neurological, Dermatologic, and Genito -urinary systems . Abbreviated physical exams will be conducted at Weeks 2, 3, 4, , 7, and 10 are limited to vital signs and symptoms unless otherwise clinically indicated. 22 Blood draw for hematology requires 5 mL and serum chemistry requires 5 mL ; hematology assessments include white blood cell (WBC) with differential, platelet co unt, hemoglobin, red blood cell (RBC) count and absolute neutrophils; chemistry includes serum assessment of sodium, calcium, total protein, albumin, creatinine, blood urea nitrogen (BUN), total bilirubin, alkaline phosp hatase, AST, ALT, potassium, chlorid e, sodium bicarbonate, lactate dehydrogenase, and glucose . 23 Repeat assessment at Baseline only if Screening Visit was performed > 2 weeks prior to dosing . 24 Blood draw for Tropo nin I or T requires 5 mL (performed at Screening and Weeks 1 through 4). 25 Blood draw for serum pregnancy test for women of childbearing potential requires 1 mL (performed at Screening and Baseline prio r to dosing). 26 Blood draw for TMB requires 20 ml of blood at Week 1 prior to dosing. 27 Blood draw for IR requires 50 mL of blood (performed at Screening and at Weeks 7, 13 and EOT). 28 Tissue biopsy sample collection may be archival or fresh at screening , and fresh tissue collected at Week 10 when feasible. Activity Screening Week Boosting EOT19 Survival FU D-28 to D -1 1 2 3 4 5 6 7 8 9 10 11 12 13 Study Day Baseline20 D-7 to D1 8 ±2 15 ±3 22 ±3 29 ±3 36 ±3 43 ±3 50 ±3 57 ±3 64 ±3 71 ±3 78 ±3 85 ±3 Q3 weeks ±3 +21 to 28 Q3 months Informed Consent X Medical History X X Demographics X ECOG PS X X PE with vital signs X21 X X X X X X19 Hematology22 and serum chemistry22 X X23 X X X X X Troponin I or T24 X X X X X Pregnancy Test25 (serum or urine) X X23 Tumor Mutation Burden Lab26 X Immunologic Response Lab27 X X X X Tissue Collection28 X X Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 54 of 95 29 EOT should be completed approximately 3 to 4 weeks following last dos e of HS-110, including premature/early termination of HS -110 treatment . 30 Tumor assessment will be evaluated by RECIST 1.1 and iRECIST . Qualifying imaging assessment for Arm 6 may be completed up to 6 weeks prior to first HS -110 administration. 31 Only sub sequent anti -cancer therapy will be recorded . 32 30 minute observation after first dose only . 33 Pembrolizumab +/ - pemetrexed will be administered every 3 weeks per package insert. 34 AEs/SAEs to be recorded up to 4 weeks after the last administration of HS-110, and followed until resolution (unless not resolvable due to underlying disease) . Activity Screening Week Boosting EOT29 Survival FU Day -28 to D -1 1 2 3 4 5 6 7 8 9 10 11 12 13 Study Day Baseline D -7 to D1 8 ±2 15 ±3 22 ±3 29 ±3 36 ±3 43 ±3 50 ±3 57 ±3 64 ±3 71 ±3 78 ±3 85 ±3 Q3 weeks ±3 +21 to 28 Q3 months Tumor Assessment by CT or MRI30 X X Q9 weeks from week 9 ECG X X ECHO or MUGA with LVEF X Verify eligibility criteria X X X Prior and Concomitant Medications X X X X X X X X X X X X X X X X X X31 HS-110 vaccination X32 X X X X X X X X X X X X X SOC Pembrolizumab +/ - pemetrexed administration33 X X X X X X Record AEs/SAEs34 X X X X X X X X X X X X X X X Survival Status X Heat Biologics, Inc. Viagenpumatucel -L Protocol HS110 -102 CONFIDENTIAL Amendment 6, 24 May 2019 Page 55 of 95 11. TREATMENT OF PATIENTS 11.1. Description of Study Drug Table 4: Investigational Product PARAMETER PRODUCT INFORMATION INN/USAN name Viagenpumatucel -L Code Name HS-110 Dosage Form Suspension for Injection (ready -to-use or concentrated) Strength / Dose 1 × 107 viable cells/ 0.5 mL Route of Administration Intradermal Dosing Regimen Arm 5: Weekly, 5 intradermal 0.1 mL injections for 18 weeks Arm 6: Weekly, 5 intradermal 0.1 mL injections for 1 3 weeks followed by 5 intradermal 0.1m L injections every 3 weeks until disease progression or unacceptable toxicity (whichever occurs first) How Supplied Ready -to-use single -dose vial : 0.6 mL (include s 0.5 mL dose plus 0.1 mL overage ) Storage Conditions ≤ - 120⁰C Stored in liquid nitrogen vapor phase 11.2. Prior and Concomitant Medications All prior and concomitant medications, including prescription and over -the-counter medications taken during the 14 days before the date of first dose, during the study treatment, and through 4 weeks post the last dose of study drug, will be documented.