Study of GNX102 in Patients With Advanced Solid Tumors
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|ClinicalTrials.gov Identifier: NCT04250597|
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : October 26, 2020
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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|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|
|Experimental: 1.0 mg/kg||
|Experimental: 3.0 mg/kg||
|Experimental: 10 mg/kg||
|Experimental: 30 mg/kg||
|Experimental: 60 mg/kg||
- 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).
- Antitumor activity of GNX102 [ Time Frame: Through study completion, an average of 2 years ]To evaluate antitumor activity of GNX102 by objective radiographic assessment
- 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
- Cmax: Maximum plasma concentration of GNX102 (μg) [ Time Frame: Through study completion, an average of 2 years ]To determine the pharmacokinetics (PK) of GNX102
- 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
- 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
- CL: Clearance of GNX102 (L/hr) [ Time Frame: 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) [ Time Frame: Through study completion, an average of 2 years ]To determine the pharmacokinetics (PK) of GNX102
- 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)
- 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
- 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
- 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
- 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
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
|Contact: Yun-Ting Liaofirstname.lastname@example.org|
|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||Recruiting|
|Saint Paul, Minnesota, United States, 55303|
|Contact: Arkadiusz Dudek, MD|
|Principal Investigator: Arkadiusz Dudek, MD|
|United States, Oregon|
|Providence Cancer Institute Earle A. Chiles Research Institute||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|
|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|
|Study Director:||Mei-Chun Yang, PhD||GlycoNex, Inc.|