Advanced Cancer, Metastatic Cancer, Solid Tumor, Unresectable Solid Neoplasm
Conditions
Brief summary
GNX102 is a humanized monoclonal antibody (mAb), an engineered biotechnology product, developed by GlycoNex that targets certain cancer cells by binding with high affinity to specific structures on cancer cells. Specifically, GNX102 binds to novel glycan structures caused by glycosylation changes in tumors. Patients with epithelial origin 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.
Interventions
DRUGGNX102
Dose Escalation
Sponsors
GlycoNex, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | Through study completion, an average of 2 years | If ≤ 1 of 6 patients has a dose limiting toxicity (DLT) after all previous dose testing the dose will be declared the Maximum Tolerable Dose (MTD). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC: Area under the concentration curve of GNX102 (μg × h/mL) | Through study completion, an average of 2 years | To determine the AUC Area under the concentration curve of GNX102 |
| t1/2: Terminal phase half-life of GNX102 (minutes) | Through study completion, an average of 2 years | To determine the pharmacokinetics (PK) of GNX102 |
| CL: Clearance of GNX102 (L/hr) | Through study completion, an average of 2 years | To determine the pharmacokinetics (PK) of GNX102 |
| Vz: Apparent volume of distribution in the terminal phase of GNX102 (L) | Through study completion, an average of 2 years | To determine the pharmacokinetics (PK) of GNX102 |
| Number of adverse events (AEs) | Through study completion, an average of 2 years | Dose-limiting AEs will be used to establish the MTD and the recommended dose for phase 2 studies (RP2D) |
| Number of toxicities | Through study completion, an average of 2 years | Toxicities will be used to establish the MTD and the recommended dose for phase 2 studies (RP2D) |
| Antitumor activity of GNX102 | Through study completion, an average of 2 years | To evaluate antitumor activity of GNX102 by objective radiographic assessment |
| Cmax: Maximum plasma concentration of GNX102 (μg) | Through study completion, an average of 2 years | To determine the pharmacokinetics (PK) of GNX102 |
| Tmax: Time to maximum plasma concentration of GNX102 (minutes) | Through study completion, an average of 2 years | To determine the pharmacokinetics (PK) of GNX102 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Outcome: Anti-drug antibody (ADA) to GNX102 (counts) | Through study completion, an average of 2 years | To evaluate the development of anti-drug antibody (ADA) to GNX102 |
| Exploratory Outcome: Serum CA 19-9, CA 125, or CEA antigen levels (counts) | Through study completion, an average of 2 years | To explore biomarkers related to participant's specific cancer type (e.g. pancreas, ovarian, or colon, respectively) to predict toxicity or response to GNX102 |
| Exploratory Outcome: GNX102 targeted antigens (counts) | Through study completion, an average of 2 years | To explore tumor expression of GNX102 targeted antigens as a biomarker to predict toxicity or response to GNX102 |
Countries
Taiwan, United States
Outcome results
None listed