Study of GNX102 in Patients With Advanced Solid Tumors
Study of GNX102 in Patients With Advanced Solid Tumors
GNX-001 is an open-label, phase 1, multicenter, dose-escalation and expansion study of GNX102
 infused every 21 days. Approximately 30 patients may be enrolled in the dose escalation
 portion of this study. Once the MTD or recommended phase 2 dose (RP2D) has been identified,
 up to 15 additional patients may be enrolled in one or two expansion cohort(s) at one or two
 dose levels recommended by the Safety Review Committee) to confirm the safety profile of the
 RP2D and provide additional information on anti-tumor activity.

 Patients with adeno- or epithelial-cancers that have a likelihood of GNX102 targeted antigen
 expression based on previous studies, including colorectal, hepatocellular, non-small cell
 lung, gastric, breast, pancreatic, cutaneous, acral, or mucosal melanoma, esophageal,
 prostate, and epithelial uterine cancers, can be screened for enrollment in the study.
GNX102 is a humanized monoclonal antibody (mAb) developed by GlycoNex. GNX102 binds with high
 affinity to branched Lewis B/Lewis Y (LeB/LeY) glycans, which are novel glycans caused by
 glycosylation changes in tumors. The monomeric LeB and LeY are blood group related antigens,
 commonly present in healthy adult tissues at low to moderate levels, but are overexpressed in
 multiple carcinomas and their presence correlates with tumor development and progression.

 Higher affinity for branched LeB/LeY glycans is intended to allow GNX102 to discriminate
 between the monomeric LeB and LeY glycans presented on normal tissues from the branched LeB
 and LeY glycans present on cancer tissues. This preferential binding to branched LeB/LeY
 versus monomeric LeB and LeY could improve the therapeutic index by both improving
 selectivity for tumor cells and reducing toxicity to normal tissues.

 The investigational product GNX102 will be administered as an intravenous infusion over one
 hour every 21 days as a single agent. One cycle is 21 days in duration. Patients may continue
 to receive study drug every 21 days without interruption between cycles unless there is
 unacceptable toxicity or experiences progressive disease. A dose delay of up to 14 days is
 permitted between cycles to address toxicities.

 The GNX102 starting dose will be 1 mg/kg and escalating to 3 mg/kg, 10 mg/kg, 30 mg/kg and 60
 mg/kg. This dosing schedule is designed to start with a dose that is anticipated to produce
 an exposure level in patients that has some potential to provide clinical benefit yet is
 many-fold below an exposure level that was associated with an acceptable safety profile in
 toxicology studies. The half-log dose escalation strategy is designed to ensure that there
 are clinically meaningful differences in GNX102 exposure between successive cohorts.

 Up to five (5) dose levels are planned during dose escalation. Dose escalation will depend on
 the number and intensity of observed toxicities as well as review of available
 pharmacokinetic (PK data). A Safety Review Committee (SRC) will review available safety and
 PK data as relevant to make recommendations related to selection of dose and schedule (dosing
 interval), as well as modifications to PK time points. At the recommendation of the SRC, a
 cohort may be repeated or intermediate dose levels between scheduled dose levels may be
 explored during the escalation phase.

 Dose escalation will follow a standard oncology 3+3 design with a dose-escalation schema.

 Up to 30 patients may be enrolled in the dose expansion cohorts. Once the MTD has been
 determined in the dose escalation phase of the study, approximately 15 additional patients
 may be enrolled in one or two dose expansion cohort(s) (at the MTD and one lower dose level)
 to further assess safety and the RP2D as well as anti-tumor activity.

 In accordance with FDA COVID-19 Guidance on the Conduct of Clinical Trials of Medical
 Products during COVID-19 Pandemic (dated March 18, 2020; updated March 27, 2020; updated
 April 16, 2020), GlycoNex and the Contract Research Organization (CRO), Linical Americas,
 supporting this study are modifying their processes and procedures in alignment with FDA
 Guidance to ensure the safety of study participants, while streamlining study conduct and
 decreasing the burden on patients and sites. The intent is to reduce visits, procedures
 and/or tests that are considered non-essential in order to assure patient safety and address
 the most important trial objectives. The SRC may determine that procedures or visits need to
 be rescheduled or omitted. The IRB will be notified promptly of such change(s) and a
 subsequent amendment will be provided in a timely manner.
Inclusion Criteria

 The 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. Patients 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. Patient has a paraffin block of non-necrotic tumor tissue available for
 immunohistochemistry (IHC) analyses, to be shipped prior to initiation of treatment.
 Processing includes an option to send formalin-fixed paraffin embedded slides [FFPE]
 slides if a tumor block is not available.

 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: patient has measurable disease per RECIST v 1.1 criteria.

 6. ECOG performance status of 0 or 1.

 7. Baseline QTC interval of ≤ 480 msec using Frederica's formula.

 8. Acceptable liver function:

 -  Bilirubin ≤ 1.5 times upper limit of normal

 -  AST (SGOT) and ALT (SGPT) ≤ 3 times upper limit of normal. If liver metastases
 are present, then ≤ 5 x 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 values.

 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

 -  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; PT/INR and 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 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.

 2. Has a positive PCR test for active COVID-19 infection or has signs or symptoms
 consistent with COVID-19 in the absence of a negative PCR test.

 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 CNS tumor.

 7. History of CNS metastases, unless previously treated and stable for at least 4 weeks
 in the absence of steroids. Patients 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 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 patient inappropriate for entry into this
 study.

 10. Clinical symptoms of pancreatitis within the past 28 days.

 11. Known active infection with HIV, hepatitis B (HBV), or hepatitis C (HCV).

 -  Patients with a history of HBV or HCV are allowed if HBV DNA or HCV RNA are
 undetectable. Patients with hepatocellular cancer on anti-viral therapy must have
 DNA levels ≤ 500 IU/ml.

 -  Patients with a history of HBV or HCV will be monitored for 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. No second malignancy which is considered active or requires concurrent treatment.

 17. For patients 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 patient inappropriate for entry into this study.