Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of GNX102 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04250597
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : August 18, 2020
Sponsor:
Collaborator:
Linical Americas
Information provided by (Responsible Party):
GlycoNex, Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Solid Tumor Metastatic Cancer Advanced Cancer Unresectable Solid Neoplasm Drug: GNX102 Phase 1

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of GNX102 in Patients With Advanced Solid Tumors
Actual Study Start Date : July 29, 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : February 2022

Arm Intervention/treatment
Experimental: 1.0 mg/kg Drug: GNX102
Dose Escalation

Experimental: 3.0 mg/kg Drug: GNX102
Dose Escalation

Experimental: 10 mg/kg Drug: GNX102
Dose Escalation

Experimental: 30 mg/kg Drug: GNX102
Dose Escalation

Experimental: 60 mg/kg Drug: GNX102
Dose Escalation




Primary Outcome Measures :
  1. maximum tolerated dose (MTD) [ Time Frame: 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 Outcome Measures :
  1. Antitumor activity of GNX102 [ Time Frame: Through study completion, an average of 2 years ]
    To evaluate antitumor activity of GNX102 by objective radiographic assessment

  2. AUC: Area under the concentration curve of GNX102 (μg × h/mL) [ Time Frame: Through study completion, an average of 2 years ]
    To determine the AUC Area under the concentration curve of GNX102

  3. Cmax: Maximum plasma concentration of GNX102 (μg) [ Time Frame: Through study completion, an average of 2 years ]
    To determine the pharmacokinetics (PK) of GNX102

  4. Tmax: Time to maximum plasma concentration of GNX102 (minutes) [ Time Frame: Through study completion, an average of 2 years ]
    To determine the pharmacokinetics (PK) of GNX102

  5. t1/2: Terminal phase half-life of GNX102 (minutes) [ Time Frame: Through study completion, an average of 2 years ]
    To determine the pharmacokinetics (PK) of GNX102

  6. CL: Clearance of GNX102 (L/hr) [ Time Frame: Through study completion, an average of 2 years ]
    To determine the pharmacokinetics (PK) of GNX102

  7. Vz: Apparent volume of distribution in the terminal phase of GNX102 (L) [ Time Frame: Through study completion, an average of 2 years ]
    To determine the pharmacokinetics (PK) of GNX102

  8. Number of adverse events (AEs) and number of toxicities [ Time Frame: Through study completion, an average of 2 years ]
    Dose-limiting AEs and toxicities will be used to establish the MTD and the recommended dose for phase 2 studies (RP2D)


Other Outcome Measures:
  1. Exploratory Outcome: GNX102 targeted antigens (counts) [ Time Frame: 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

  2. Exploratory Outcome: Serum LeB / LeY antigen levels (counts) [ Time Frame: Through study completion, an average of 2 years ]
    To explore serum LeB / LeY antigen levels as a potential biomarker to predict toxicity or response to GNX102

  3. Exploratory Outcome: Serum tumor-specific antigen levels (counts) [ Time Frame: Through study completion, an average of 2 years ]
    To explore biomarkers related to cancer type to predict toxicity or response to GNX102

  4. Exploratory Outcome: Anti-drug antibody (ADA) to GNX102 (counts) [ Time Frame: Through study completion, an average of 2 years ]
    To evaluate the development of anti-drug antibody (ADA) to GNX102



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04250597


Contacts
Layout table for location contacts
Contact: Yun-Ting Liao 886-2-26974168 ytliao@glyconex.com.tw

Locations
Layout table for location information
United States, California
USC Norris Comprehensive Cancer Center and HOAG Recruiting
Los Angeles, California, United States, 90033
Contact: Diana Hanna, MD         
Principal Investigator: Diana Hanna, MD         
United States, Minnesota
Regions Cancer Care Center Not yet recruiting
Saint Paul, Minnesota, United States, 55303
Contact: Arkadiusz Dudek, MD         
Contact       Arkadiusz.Z.Dudek@HealthPartners.com   
Principal Investigator: Arkadiusz Dudek, MD         
United States, Oregon
Providence Cancer Institute Earle A. Chiles Research Institute Not yet recruiting
Portland, Oregon, United States, 97213
Contact: Rachel Sanborn, MD         
Principal Investigator: Rachel Sanborn, MD         
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Anthony J Olszanski, MD, RPh         
Principal Investigator: Anthony J Olszanski, MD, RPh         
United States, Wisconsin
Medical College of Wisconsin Cancer Center Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Ben George, MD         
Principal Investigator: Ben George, MD         
Taiwan
China Medical University Hospital Not yet recruiting
Taichung City, Taiwan, 404472
Contact: Li-Yuan Bai, MD, MMS, PhD         
Principal Investigator: Li-Yuan Bai, MD, MMS, PhD         
National Cheng Kung University Hospital Not yet recruiting
Tainan, Taiwan, 704
Contact: Chia-Jui Yen, PhD         
Principal Investigator: Chia-Jui Yen, PhD         
Sponsors and Collaborators
GlycoNex, Inc.
Linical Americas
Investigators
Layout table for investigator information
Study Director: Mei-Chun Yang, PhD GlycoNex, Inc.
Layout table for additonal information
Responsible Party: GlycoNex, Inc.
ClinicalTrials.gov Identifier: NCT04250597    
Other Study ID Numbers: GNX-001
First Posted: January 31, 2020    Key Record Dates
Last Update Posted: August 18, 2020
Last Verified: July 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes