Drug accountability will be strictly maintained. 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 24 of 60 Version 2.0 - 11 Feb 2020 Confidential - Entire Page 8. This trial will be conducted according to G ood Clinical Practice (GCP), the protocol and applicable regulatory requirements. 2.8 Patient Population This study will enroll adult male and female patients of age ≥ 18 years with progressive or metastatic solid tumor types, who have failed standard treatment and/or for whom no other effective or safe treatment is availabl e or appropriate . 3.0 TRIAL OBJECTIVES AND PURPOSE Primary : • To evaluate safety and tolerability of HS- 130 in combination with HS -110 in patients with solid tumors refractory to Standard of Care (SOC) • To determine the recommended phase 2 dose (RP2D) of the combination HS -130 and HS -110 in patients with solid tumors refractory to SOC Secondary : • To determine clinical response to combination treatment with HS -130 and HS -110 Exploratory : • To study the immunological effect generated by HS -130 and HS -110 by evaluating proportions of natural killer (NK) and T cell subsets for levels of activation, memory and exhaustion using flow cytometry • To eval uate patient archival tumor tissue for overexpressed Cancer Testis Antigens (CTAs) and shared antigen expression with HS-110 • To evaluate immune reactivation response to CTA expressed in HS -110 (e.g. by ELISPOT) • To determine the presence of a specific cyto kine/chemokine signature in response to combination treatment with HS -130 and HS -110, or any other unspecific inflammatory response • Genomic , immunohistochemical and proteomic analyses of tumor tissue (pre- dose and on -treatment biopsy) to identify biomarker s predictive of response or resistance to HS-110/HS -130, for example by multiplex immunohistochemistry (mIHC) • Assess immunologically active dose based on flow cytometry analysis of blood, using immune marker panels of activation and suppression as defined in section 8.6.1 . 4.0 TRIAL DESIGN 4.1 Overview of Trial Design This is an open -label, non-controlled, first -in-human, Phase I study of combined intradermal administration of HS -130 and HS -110 to patients with advance d solid tumors refractory to SOC. Escalating doses of the viable, replication-incompetent, human whole cell vaccines, HS-130 and HS -110 will be administered to patients via intradermal injections /reinjections (up to 10 total ) on Day 1 of a two - 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 25 of 60 Version 2.0 - 11 Feb 2020 Confidential - Entire Page week cycle . The length of each cycle is two weeks, and the DLT window of observation includes the safety data obtained from the first two treatment cycles, Cycle 1 and Cycle 2 ( 4 weeks ). Seven dose levels will be explored, and patients will receive separate escala ting doses of HS-130 and HS- 110 in alternating fixed 1:1 or 2:1 ratios based on the amount of secreted OX40L -Ig (HS -130) and gp96- Ig fusion protein (HS -110) per cell of the drug product (Section 6.1.1). The starting dose of HS -130/HS -110 combination is based on the dose-ranging studies conducted in animal model s of T cell expansion and tumor challenge, as well as established clinical experience from HS-110. In the absence of progressive disease and intolerable toxicity after Cycle 2, the patient can continue the combination treatment of HS-130/HS-110 administered every 2 -weeks until disease progression, death, patient ’s withdrawal of consent, I nvesti gator decision to discontinue treatment , or intolerable toxicity, whichever occurs first. Immune response may be a delayed effect, and in immuno -oncology, treatment beyond first progression is commonly used in situations where clinical progression is as ymptomatic and/or is not likely to result in life-threatening complications with further progression. Therefore, at the discretion of the I nvestigator the treatment with the therapeutic vaccines HS-130/HS -110 may continue despite evidence of disease progression , if the investigator considers this of a potential clinical benefit for the patient, and the following criteria are met: • No other approved palliative or curative salvage therapy exists for the indication (e.g. resection of pulmonary metastases in osteosarcoma patients).