Study of GNX102 in Patients With Advanced Solid Tumors

Inclusion Criteria

The target study population consists of adult patients with advanced solid tumors that meet all of the following criteria to be enrolled into this study:

1. Age ≥ 18 years.

2. Participants with histologically confirmed solid tumors with a likelihood of expression of GNX102 targeted antigens, which are limited to:

   • colorectal
   • hepatocellular
   • non-small cell lung
   • gastric
   • breast
   • bladder
   • pancreatic
   • melanoma (cutaneous, acral, or mucosal)
   • esophageal
   • prostate
   • ovarian
   • cervical
   • epithelial uterine cancers.
3. Participant has a paraffin block of non-necrotic tumor tissue available for immunohistochemistry (IHC) analyses, to be shipped and confirmed adequate by NeoGenomics pathologist prior to initiation of treatment.
4. Advanced, unresectable (local, regionally, recurrent not amenable to curative therapy) or metastatic disease that has no standard therapeutic option with a proven clinical benefit, are intolerant to or have refused all standard of care options with demonstrated clinical benefit.
5. Expansion Phase only: Participant has measurable disease per response evaluation criteria in solid tumors (RECIST) v 1.1 criteria.
6. Eastern Cooperative Group (ECOG) performance status of 0 or 1.
7. Baseline Q-T corrected interval (QTc) interval of ≤ 480 msec using Frederica's formula.

8. Acceptable liver function:

   • Bilirubin ≤ 1.5 times upper limit of normal
   • Aspartate transaminase (serum glutamic-oxaloacetic transaminase) [AST (SGOT)] and alanine transaminase (serum glutamic-pyruvic transaminase) [ALT (SGPT)] ≤ 3 times upper limit of normal. If liver metastases are present, then ≤ 5 x upper limits of normal (ULN) is allowed, and
   • Serum albumin ≥ 2.5 g/dL.
9. Acceptable renal function, defined as calculated creatinine clearance > 30 mL/min per institution laboratory value.

10. Acceptable hematologic status:

    • Hemoglobin ≥ 8 g/dL (no packed red blood cell [PRBC] transfusions allowed within 2 weeks)
    • Absolute neutrophil count (ANC) ≥ 1500 cells/mm^3 or ≥ 1.5 x 10^9/L, and
    • Platelet count ≥ 100,000 platelets/mm^3 or ≥ 100 x 10^9/L, and
    • Absolute reticulocyte count (x10^9/L) ≤ ULN.
11. Serum haptoglobin (mg/dL) ≥ LLN.
12. Acceptable coagulation status with fibrinogen above LLN; prothrombin time/international normalized ratio (PT/INR) and partial thromboplastin time (PTT) ≤ 1.5 times upper limit of normal (may be on a stable dose of coumadin with stable INR in the therapeutic range).
13. Life expectancy of at least 3 months.
14. Signed Institutional Review Board (IRB)-approved informed consent.
15. Able and willing to comply with the protocol for the duration of the study, including undergoing treatment and scheduled visits and examinations.
16. A negative serum pregnancy test, if female of child-bearing potential.
17. For men and women of child-bearing potential, agreement to the use of at least 1 highly effective contraceptive method(s) during the study and in the 3 months following the last dose of GNX102.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from participation in this study:

1. Has any other malignancy not listed in Inclusion Criteria 2. Note: Participants with prior early-stage cervical cancer, basal cell carcinoma (BCC) or squamous cell carcinoma that has been successfully treated with curative intent and participant has been disease free for >2 years may be enrolled.
2. Has a positive polymerase chain reaction (PCR) test for active COVID-19 infection or has signs or symptoms consistent with COVID-19 in the absence of a positive PCR test within 2 weeks from date of consent.
3. Has New York Heart Association Class III or IV heart disease.
4. History of myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, within the past 6 months.
5. History of cerebral vascular accident or transient ischemic attack within the past 6 months.
6. History of primary central nervous system (CNS) tumor.
7. History of CNS metastases, unless previously treated and stable for at least 4 weeks in the absence of steroids. Participants with meningeal carcinomatosis are excluded regardless of treatment.
8. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy within 72 hours of start of therapy.
9. Active, nonmalignant gastrointestinal (GI) disease requiring treatment (such as inflammatory bowel disease, Crohn's disease, colitis) that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, which would make the participant inappropriate for entry into this study.
10. Clinical symptoms of pancreatitis within the past 28 days.

11. Known active infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C.

    • Patients with a history of hepatitis B or C are allowed if HBV deoxyribonucleic acid (DNA) or Hep C ribonucleic acid (RNA) are undetectable. Participants with hepatocellular cancer on antiviral therapy must have DNA levels ≤ 500IU/ml.
    • Participants with a history of HBV will be monitored for HBV reactivation while on study.
12. Pregnant or nursing women.
13. Treatment with radiation therapy within 14 days prior to dosing with GNX102.
14. Major surgery within 14 days prior to dosing with GNX102.
15. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.
16. Second malignancy which is considered active or requires concurrent treatment.

17. For participants with hepatocellular carcinoma

    • Ascites requiring more than 1 paracentesis per month
    • History of hepatic encephalopathy within 12 months of study entry
18. History of bleeding esophageal or gastric varices within 6 months of study entry.
19. Prior or ongoing cancer treatment, including investigational treatment within 5 half-lives or 21 days whichever is less, prior to dosing with GNX102 and 6 weeks for nitrosoureas or mitomycin C.
20. Allergies to any excipients in GNX102 (i.e., L-histidine, sucrose, Polysorbate 80).
21. Severe acute or chronic medical or psychiatric conditions or other laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, which would make the participant inappropriate for entry into this study.