Clinical Trials /

Study of GNX102 in Patients With Advanced Solid Tumors

NCT04250597

Description:

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.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Uterine Corpus Neoplasm
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of GNX102 in Patients With Advanced Solid Tumors
  • Official Title: A Phase I Study of GNX102 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GNX-001
  • NCT ID: NCT04250597

Conditions

  • Solid Tumor
  • Metastatic Cancer
  • Advanced Cancer
  • Unresectable Solid Neoplasm

Interventions

DrugSynonymsArms
GNX1021.0 mg/kg

Purpose

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.

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). At the recommendation of the Safety Review Committee (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.
    

Trial Arms

NameTypeDescriptionInterventions
1.0 mg/kgExperimental
  • GNX102
3.0 mg/kgExperimental
  • GNX102
10 mg/kgExperimental
  • GNX102
30 mg/kgExperimental
  • GNX102
60 mg/kgExperimental
  • GNX102

Eligibility Criteria

        Inclusion Criteria

        The study population consists of adult patients with advanced solid tumor disease 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. 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.

          4. Measurable disease per RECIST v 1.1 (primary or metastatic disease).

          5. ECOG performance status of 0 or 1.

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

          7. 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

               -  Serum albumin ≥ 2.5 g/dL.

          8. Acceptable renal function, defined as calculated creatinine clearance > 30 mL/min per
             institution laboratory values.

          9. Acceptable hematologic status:

               -  Hemoglobin ≥ 8 g/dL (no PRBC transfusions allowed within 2 weeks)

               -  Absolute neutrophil count (ANC) ≥ 1500 /μL

               -  Platelet count ≥ 100,000/ μL

               -  Absolute reticulocyte count < ULN.

         10. Serum haptoglobin > LLN.

         11. Acceptable coagulation status with fibrinogen, PT, PTT and INR ≤ 1.5 times upper limit
             of normal (May be on a stable dose of coumadin with stable INR in the therapeutic
             range).

         12. Life expectancy of at least 3 months.

         13. Signed IRB-approved informed consent.

         14. Able and willing to comply with the protocol for the duration of the study, including
             undergoing treatment and scheduled visits and examinations.

         15. A negative serum pregnancy test (if female of child-bearing potential).

         16. 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. Does not have one of the malignancies listed in Inclusion Criteria #2.

          2. New York Heart Association Class III or IV heart disease.

          3. History of myocardial infarction, unstable angina, coronary/peripheral artery bypass
             graft, within the past 6 months.

          4. History of cerebral vascular accident or transient ischemic attack within the past 6
             months.

          5. History of primary CNS tumor.

          6. 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.

          7. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
             therapy within 72 hours of start of therapy.

          8. 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.

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

         10. Known active infection with HIV, hepatitis B, or hepatitis C.

               -  Patients with a history of hepatitis B or C are allowed if HBV DNA or Hep C RNA
                  are undetectable. Patients with hepatocellular cancer on antiviral therapy must
                  have DNA levels ≤ 500IU/ml.

               -  Patients with a history of HBV will be monitored for HBV reactivation while on
                  study.

         11. Pregnant or nursing women.

         12. Treatment with radiation therapy within 14 days prior to dosing with GNX102.

         13. Major surgery within 14 days prior to dosing with GNX102.

         14. History of autoimmune hemolytic anemia or autoimmune thrombocytopenia.

         15. No second malignancy which is considered active or requires concurrent treatment.

         16. For patients with hepatocellular carcinoma

               -  Ascites requiring more than 1 paracentesis per month

               -  History of hepatic encephalopathy within 12 months of study entry

         17. History of bleeding esophageal or gastric varices within 6 months of study entry.

         18. 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.

         19. Allergies to any excipients in GNX102 (i.e., L-histidine, sucrose, Polysorbate 80).

         20. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:maximum tolerated dose (MTD)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description: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

Measure:Antitumor activity of GNX102
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To evaluate antitumor activity of GNX102 by objective radiographic assessment
Measure:AUC: Area under the concentration curve of GNX102 (μg × h/mL)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To determine the AUC Area under the concentration curve of GNX102
Measure:Cmax: Maximum plasma concentration of GNX102 (μg)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To determine the pharmacokinetics (PK) of GNX102
Measure:Tmax: Time to maximum plasma concentration of GNX102 (minutes)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To determine the pharmacokinetics (PK) of GNX102
Measure:t1/2: Terminal phase half-life of GNX102 (minutes)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To determine the pharmacokinetics (PK) of GNX102
Measure:CL: Clearance of GNX102 (L/hr)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To determine the pharmacokinetics (PK) of GNX102
Measure:Vz: Apparent volume of distribution in the terminal phase of GNX102 (L)
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:To determine the pharmacokinetics (PK) of GNX102
Measure:Number of adverse events (AEs) and number of toxicities
Time Frame:Through study completion, an average of 2 years
Safety Issue:
Description:Dose-limiting AEs and toxicities will be used to establish the MTD and the recommended dose for phase 2 studies (RP2D)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Accelovance

Last Updated

January 30, 2020