Biopsy should be collected for patients with accessible tumor lesions, incl. metastases (e.g. lymph node metastases) where it is consider ed feasible without a risk of complications for the patient. Coagulation parameters and blood cells should be assessed and reviewed per institutional standard prior to any biopsy. l: HS-130 and HS -110 will be administered via intradermal injections/re -injections (up to 10 total) on Day 1 of each cycle , depending on the assigned dose level . (See section 6.1 Drug preparation and administration) m: All assessments should be performed at 30 days ± 3 days after the last treatment, during the 30 -day safety follow -up visit. n: If a patient stops treatment for any other reason than progressive disease, radiological assessments will continue every 12 weeks st arting from the date of patient’s last dose until disease progression or initiation of new anti -cancer treatment. o: Survival status and subsequent anti -cancer therapy information will be collected approximately every 12 weeks in a clinic visit, or by telephone from the time of disease progression or initiation of new anti -cancer treatment until death. p: Each cycle is 14 days. Heat Biologics Protocol No. HS130 -001 A Phase I Study of HS -130 in combination with HS-110 in patients with solid tumors HS130- 001 38 of 60 Version 2.0 - 11 Feb 2020 Confidential - Entire Page 7.2 Pre-treatment Within 28 days from C1D1: • Sign informed consent • ECG in triplicate (a standard 12 -lead ECG is taken while patient is in a semi -recumbent position) • Medical history including prior treatments and surgeries, prior medications, and pre-existing clinical signs and symptoms • Imaging for tumor measurements by RECIST 1.11 • Fresh Biopsy (archival tissue may be submitted if collected less than 6 -months prior to C1D1 and the local pathologist confirms that an adequate amount of tissue/tumor cells exist to allow compl etion of all testing as outlined in the Tumor Biopsy Collection Manual) . Note that coagulation tests should be reviewed prior to procedure per institutional standards. Within 7 days from C1D1: • Physical exam • Weight • Vital signs (blood pressure, heart rate, respiratory rate, and temperature ) • ECOG performance status (APPENDIX I) • Pregnancy test for women of childbearing potential (i.e. not surgically sterile or post -menopausal > 1 year) • Blood draw for Hematology, Blood chemistry 7.3 During Treatment Each cycle will be 14 -days. 7.3.1 Cycle 1 7.3.1.1 Cycle 1 Day 1 ± 2 days (Week 1) • Physical Exam (may be done within 3 days prior) • Weight (may be done within 3 days prior) • Vital signs (blood pressure, heart rate, respiratory rate, and temperature : Before HS130/HS110 treatment; after HS130/HS110 treatment at 30 mins ( ±5m), and 1hr (±5m)) • ECG in triplicate ( a standard 12 -lead ECG is taken while patient is in a semi-recumbent position ; pre-dose) • ECOG performance status (may be done within 3 days prior) (APPENDIX I) • Blood draw for Hematology (may be done within 3 days prior) • Blood draw for Blood chemistry tests (may be done within 3 days prior) • HS-130/ HS-110 administration • Blood draw for immune response labs ( Immunological Effect /Immune re-activation) (Pre-dose) • Blood draw for Cytokines/Chemokines (Pre-dose, and 2 hr ± 10 minutes after completion of HS130/HS110 treatment ) • Record Concomitant medications (Update prior medications if applicable) • Record Adverse events 7.3.1.2 Cycle 1 Day 8 ± 2 days (Week 2) • Physical Exam Heat Biologics Protocol No. HS130 -001 A Phase I Study of HS -130 in combination with HS-110 in patients with solid tumors HS130- 001 39 of 60 Version 2.0 - 11 Feb 2020 Confidential - Entire Page • Weight • Vital signs (blood pressure, heart rate, respiratory rate, and temperature ) • ECOG Performance status ( APPENDIX I) • Blood draw for immune response labs (Immunological Effect/Immune re-activation) • Record Concomitant medications • Record Adverse events 7.3.2 Cycle 2 7.3.2.1 Cycle 2 Day 1 ± 2 days (Week 3) • Physical Exam • Weight • Vital signs (blood pressure, heart rate, respiratory rate, and temperature : Before HS130/HS110 treatment; after HS130/HS110 treatment at 30 mins ( ±5m), and 1hr (±5m)) • ECG in triplicate (a standard 12 -lead ECG is taken while patient is in a semi -recumbent position; pre-dose) • ECOG Performance status (APPENDIX I) • Blood draw for Hematology • Blood draw for Blood chemistry tests • Blood draw for immune response labs (Immunological Effect/ immune re-activation) (Pre-dose) • Blood draw for Cytokines/Chemokines (Pre-dose, and 2 hr ± 10 minutes after completion of HS130/HS110 treatment ) • Record Concomitant medications • Record Adverse events • HS-130/ HS-110 administration 7.3.2.2 Cycle 2 Day 8 ± 2 days (Week 4) • Physical Exam • Weight • Vital signs (blood pressure, heart rate, respiratory rate, and temperature ) • ECOG Performance status ( APPENDIX I) • Blood draw for immune response labs (Immunological Effect/ Immune re-acti vation) • Record Concomitant medications • Record Adverse events 7.3.3 Cycle 3 and Beyond (Day 1 ± 2 days) • Physical Exam • Weight • Vital signs (blood pressure, heart rate, respiratory rate, and temperature only before HS130/HS110 treatment ) • ECG in triplicate (a standard 12 -lead ECG is taken while patient is in a semi -recumbent position) (pre-dose) • ECOG Performance status (APPENDIX I) • Blood draw for Hematology Heat Biologics Protocol No. HS130 -001 A Phase I Study of HS -130 in combination with HS-110 in patients with solid tumors HS130- 001 40 of 60 Version 2.0 - 11 Feb 2020 Confidential - Entire Page • Blood draw for Blood chemistry tests • Blood draw for Cytokines/Chemokines (Only if patient is symptomatic ) • Record Concomitant medications • Record Adverse events • HS-130/HS -110 administration • On-treatment Biopsy ( within 5 -14 days after patient completes 2nd dose of HS-130/HS -110) . Note that coagulation tests should be reviewed prior to procedure per institutional standards. • Imaging for tu mor measurements by RECIST 1.11 (every 8 -weeks ± 1 week from C1D1 until disease progression ) 7.4 30-Day Safety Follow up Visit from Last Dose (±3 days ) The following assessments will be performed at 30 days ± 3 days of the last treatment for all patients who have discontinued treatment with HS -130/HS -110: • Physical Exam • Weight • Vital signs (blood pressure, heart rate, respiratory rate, and temperature ) • ECG in triplicate (a standard 12 -lead ECG is taken while pa tient is in a semi -recumbent position) • ECOG Performance status (APPENDIX I) • Blood draw for Hematology • Blood draw for Blood chemistry tests • Blood draw for immune response labs (Immunological Effect/ Immune re-activation) • Record Concomitant medications • Record Adverse events 7.5 Post -treatme nt Follow- up (± 1 week) The following assessments will be performed every 12 -weeks starting from the date of last dose for any patient that stop s treatment for any reason other than progressive disease until disease progression or if the patient starts a new treatment. Any AEs deemed related to study drug will also be recorded. • Record concomitant medications and/or treatments • Record Adverse events • Imaging for tumor measurements (CT scan or MRI) 7.6 Survival Follow -up (± 2 week s) The survival follow -up period refers to the time between disease progression (or confirmed disease progression in cases where Investigator treats beyond initial progression as outlined in section 8.2 ) and patient death. Survival status and subsequent anti -cancer therapy will be collected approximately every 12 weeks in a clinic visit, or by telephone. Patients who withdraw consent for stud y procedures should still be followed for survival and/or public records searched as per FDA guidance issued October 2008 entitled “Guidance for Sponsors, Clinical Investigators, and IRBs: Data Retention When Subjects Withdraw from FDA -Regulated Clinical T rials”. Heat Biologics Protocol No. HS130 -001 A Phase I Study of HS -130 in combination with HS-110 in patients with solid tumors HS130- 001 41 of 60 Version 2.0 - 11 Feb 2020 Confidential - Entire Page 8.0 STUDY ASSESSMENTS 8.1 Safety Assessments 8.1.1 Safety Analysis Safety data will be tabulated for all patients and include vital signs, laboratory parameters, and adverse events. 8.1.2 Reporting of Adverse Events 8.1.2.1 Adverse Events An adverse event (AE) is any untow ard medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An adverse event can be any unfavorable and unintended sign (including a l aboratory finding), symptom or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The AE reporting period starts on Cycle 1 Day 1; if an AE occurs before the first dose of study treatment it will be captured as baseline and considered a part of the medical history ; however, if the AE is directly attributed to a study procedure prior to C1D1, it may be reported as an AE At each evaluation , patients should be interviewed in a non-directed manner to elicit potential adverse reactions from the patient. The occurrence of an adverse event will be based on changes in the patient’s physical examination, laboratory results, and/or signs and symptoms. All adverse events (except G rade 1 and 2 laboratory abnormalities that do not require an intervention), regardless of causal relationship, are to be recorded in the case report form and source documentation. The Investigator must determine the intensity of any advers e events according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5 .0 (APPENDIX II) and their causal relationship. Those AEs not covered by these criteria will be graded as follows: 1. Mild: Discomfort noticed, but no disruption of normal daily activity. Prescription drug not ordinarily needed for relief of symptom but may be given because of personality of patient. 2. Moderate: Discomfort sufficient to reduce or affect normal daily activity. Patient is able to continue in study; treatment for symptom may be needed. 3. Severe: Incapacitating, severe discomfort with inability to work or to perform normal daily activity. Severity may cause cessation of treatment with test drug; treatment for symptom may be given and/or patient hospitalized. 4. Life-Threatening: Symptom(s) place the patient at immediate risk of death from the reaction as it occurred; it does not include a reaction that, had it occurred in a more serious from, might have caused death. 5.