Study of AM003 in Patients With Locally Advanced and Metastatic Solid Tumors

Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent.

2. Capable of providing signed informed consent, which includes compliance with therequirements of this protocol.

3. Participants with histologically confirmed locally advanced/metastatic solid tumorswho received and progressed after or were intolerant to at least 1 prior systemictherapy (unless no Standard of Care therapy exists) and are not candidates for anytherapy known to confer clinical benefit. Eligible for recruitment are participants with a variety of solid tumors such as:

• Head and neck cancers

• Thyroid cancers

• Soft tissue sarcoma

• Colorectal cancers

• Skin (melanoma and non-melanoma),

• other cancer indications may be considered, but require sponsor approval NOTE:prior exposure to PD-1 or PDL-1 inhibitors are permitted.

4. Lesions that are amenable to IT injection (by visual inspection, palpation,ultrasound or CT guidance). At least one measurable lesion must be amenable to bothIT injection and biopsy. A measurable distant, discrete lesion that is also amenableto biopsy is optional.

5. All participants must have measurable disease as defined by RECIST 1.1. Measurabledisease is defined as at least one lesion that can be accurately measured bycomputed tomography (CT), magnetic resonance imaging (MRI), or caliper measurementby clinical exam, in at least one dimension (longest diameter to be recorded).

5.1. For cohort 1 (dose level 1) participant must have at least one lesion ≥ 1.5 cm 5.2. For cohorts 2 and 3 (dose levels 2&3), participant should preferably have atleast one lesion ≥ 2.5cm and ≥ 5cm for cohorts 2 and 3 respectively. For cases inwhich no such single lesion can be identified, the total dose of AM003 may be splitamong several lesions or between a lesion and local SC administration(s).

6. Personalized AM003 sequence identified for the participant during the pre-screeningperiod or previous related studies.

7. Eastern Cooperative Oncology Group (ECOG) performance status score ≤1.

8. Life expectancy of >3 months.

9. Have adequate organ function as defined by the following laboratory values within 7days of dosing the first dose of AM003: System Lab Value Hematology Absolute neutrophil count ≥ 1,000/μl Platelets ≥ 100,000/ul Hemoglobin ≥ 9 g/dL Coagulation International Normalized Ratio (INR) orProthrombin Time (PT) Partial Thromboplastin Time (PTT) or Activated PartialThromboplastin Time(aPTT) <1.5 × ULN unless participant is receiving anticoagulanttherapy as long as PT or PTT is within therapeutic range of intended use ofanticoagulants Renal Serum creatinine ≤ 1.5 x ULN or creatinine clearance (observedor estimated using the Cockcroft-Gault equation) ≥ 45 mL/min Hepatic Total bilirubin ≤ 1.5 x ULN (except participants with Gilbert syndrome who must have a totalbilirubin level of < 3.0 x ULN) AST/ALT ≤ 3.0 x upper limits of normal (ULN) or ≤ 5.0 x ULN in participants with hepatocellular carcinoma or if liver metastases arepresent

10. Male and female participants of child-bearing potential must agree to use highlyeffective contraception while enrolled in the study and receiving the experimentaldrug, and for at least 3 months after the last treatment. Female participants ofchild-bearing potential must have a negative serum pregnancy test confirmed within 7days of receiving the initial dose of AM003 therapy.

Exclusion Criteria:

1. Clinical evidence of active central nervous system (CNS) disease NOTE: Participantsare eligible if brain metastases are adequately treated and participants areneurologically stable (except for residual signs or symptoms related to the centralnervous system (CNS) treatment) for at least 2 weeks prior to enrollment without theuse of corticosteroids or are on a stable or decreasing dose of≤ 10 mg dailyprednisone (or equivalent)

2. History of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA)or subarachnoid hemorrhage within six months prior to the first date of studytreatment.

3. Participants with congestive heart failure (≥NYHA class 3) or unstable anginapectoris.

4. Active, known or suspected autoimmune disease. Participants with type I diabetesmellitus, hypothyroidism only requiring hormone replacement, skin disorders (such asvitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditionsnot expected to recur in the absence of an external trigger are permitted to enroll.

5. Condition requiring systemic treatment with either corticosteroids (> 10 mg dailyprednisone equivalent) or other immunosuppressive medications within 14 days ofstart of study treatment. Inhaled or topical steroids, and adrenal replacementsteroid doses < 10 mg daily prednisone equivalent, are permitted in the absence ofactive autoimmune disease.

6. Prior severe hypersensitivity reaction to treatment with a monoclonal antibody

7. Has not fully recovered from any effects of major surgery, and be free ofsignificant detectable infection. Surgeries that required general anesthesia must becompleted at least 2 weeks before first study drug administration. Surgery requiringregional/epidural anesthesia must be completed at least 72 hours before first studydrug administration and participants should be recovered.

8. History of organ transplant.

9. Positive antibody and antigen tests for hepatitis virus B (HBV), hepatitis virus C (HCV) and human immunodeficiency virus (HIV). In the case of positive antibodies anda negative antigen test for hepatitis virus B or negative PCR for hepatitis virus C (representing convalescence) inclusion is permitted.

10. Any Serious illness, uncontrolled inter-current illness, psychiatric illness, activeof uncontrolled infection or other medical history, including laboratory results,which, in the opinion of the Investigator, would preclude the participant fromadhering to the protocol or would increase the risk associated with studyparticipation or study drug administration or interfere with the interpretation ofstudy results.

11. Participant received other investigational therapy, definitive radiation within 2weeks, immunotherapy or treatment with anticancer medications within 28 days or atleast 5 half-lives prior to the first dose of treatment, whichever is less.

12. Participant is currently not recovered to baseline or CTCAE Grade 1 from the AEs dueto cancer therapeutics administered more than 28 days prior to the first dose oftreatment except for alopecia and peripheral neuropathy

13. Pregnant or breastfeeding women.