Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (GLIMMER-01)
Study Details
Study Description
Brief Summary
This is a Phase 1/2, first-in-human, open-label, dose escalation and dose-expansion study of E-602, administered alone and in combination with pembrolizumab.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
This study is being conducted to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor activity of E-602 in subjects with advanced cancers.
Phase 1 of the study consists of dose escalation cohorts of E-602 as a monotherapy and in combination with pembrolizumab. Dose escalation will utilize a modified 3+3 design. Any Phase 1 cohort may be backfilled, up to a total of 15 subjects to obtain additional safety, PK, and pharmacodynamic data at a particular dose level. Phase 1 will treat subjects with melanoma, ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer. The safety and pharmacodynamic data will be evaluated to identify the maximum tolerated dose and recommended Phase 2 dose level for E-602 as monotherapy and in combination with pembrolizumab.
Phase 2 consists of dose-expansion disease cohorts in subjects with 3 types of advanced tumors: melanoma, NSCLC, and a third type to be determined (ovarian, colorectal, pancreatic, breast, gastric/EGJ, head and neck, or urothelial) based on available data. Phase 2 includes cohorts of E-602 as monotherapy and E-602 in combination with pembrolizumab. For each cohort in Phase 2, Simon's minimax 2-stage design will be used.
The study is seeking to enroll a total of up to 267 subjects (up to 81 in Phase 1 and up to 186 in Phase 2). Subjects will participate in the study for about 16 months.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Dose Escalation - Monotherapy Subjects will receive E-602 as monotherapy. Planned monotherapy dose levels: 1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg. |
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
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Experimental: Dose Escalation - Combination Subjects will receive E-602 in combination with pembrolizumab. E-602 dose(s): Will be initiated at dose level(s) that have previously completed dosing and DLT assessments as monotherapy. Pembrolizumab dose: 200 mg. |
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
Biological: Pembrolizumab
Subjects will receive pembrolizumab (administered once every 3 weeks, via IV infusion).
Other Names:
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Experimental: Expansion - Monotherapy Subjects will receive E-602 as monotherapy at the recommended Phase 2 dose determined in Phase 1. |
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
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Experimental: Expansion - Combination Subjects will receive E-602 in combination with pembrolizumab. E-602 dose: Subjects will receive E-602 at the recommended Phase 2 dose determined in Phase 1 in combination with pembrolizumab. Pembrolizumab dose: 200 mg. |
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
Biological: Pembrolizumab
Subjects will receive pembrolizumab (administered once every 3 weeks, via IV infusion).
Other Names:
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Outcome Measures
Primary Outcome Measures
- Incidence of AEs and SAEs (Phase 1) [15 Months]
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
- Dose-Limiting Toxicities (Phase 1) [21 days]
Incidence of dose-limiting toxicities (DLTs) within a modified 3+3 trial design
- Immune-Related Toxicities (Phase 1) [15 Months]
Incidence of immune-related toxicities
- Objective Response Rate (Phase 2) [12 Months]
Objective response rate of confirmed complete response and partial response
- Duration of Response (Phase 2) [16 Months]
Duration of Response of confirmed complete response or partial response.
- Progression Free Survival (Phase 2) [15 Months]
Time from first study treatment dose until the first date when progressive disease (PD) is objectively documented or death from any cause
- Overall Survival (Phase 2) [15 Months]
Time from first study treatment dose until death
Secondary Outcome Measures
- Noncompartmental PK Parameters of E-602 (Phase 1) [12 Months]
Maximum plasma concentration (Cmax)
- Noncompartmental PK Parameters of E-602 (Phase 1) [12 Months]
Area under the plasma concentration-time curve (AUC)
- Subjects with Antidrug Antibodies (Phase 1) [13 Months]
Number and percentage of subjects who develop detectable antidrug antibodies
- Objective Response Rate (Phase 1) [12 Months]
Objective response rate of confirmed complete response and partial response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST).
- Duration of Response (Phase 1) [16 Months]
Duration of Response of confirmed complete response or partial response
- Progression Free Survival (Phase 1) [15 Months]
Time from first dose to first evidence of radiographically detectable disease or death from any cause
- Overall Survival (Phase 1) [15 Months]
Time from first study treatment dose until death
- Incidence of AEs and SAEs (Phase 2) [15 Months]
Incidence of adverse events (AEs) and serious adverse events (SAEs) graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
- Immune-Related Toxicities (Phase 2) [16 Months]
Incidence of immune-related toxicities
- Noncompartmental PK Parameters of E-602 (Phase 2) [12 Months]
Maximum plasma concentration (Cmax)
- Noncompartmental PK Parameters of E-602 (Phase 2) [12 Months]
Area under the plasma concentration-time curve (AUC)
- Subjects with Antidrug Antibodies (Phase 2) [13 Months]
Number and percentage of subjects who develop detectable antidrug antibodies
Eligibility Criteria
Criteria
Key Inclusion Criteria:
- Subjects with advanced or relapsed/refractory melanoma, ovarian cancer, NSCLC, colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer who have failed prior therapies.
- Subjects with melanoma, NSCLC, head and neck cancer, urothelial cancer, or mMSI-H or dMMR colorectal cancer must have had prior anti-PD-(L)1 pathway therapy and been deemed resistant (had progression on therapy or within 3 months of discontinuation of therapy).
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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Subject has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
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Adequate bone marrow, coagulation, renal function, and liver function as determined by laboratory tests
Key Exclusion Criteria:
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For cohorts receiving E-602 and pembrolizumab combination therapy:
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Prior moderate or severe hypersensitivity to pembrolizumab or its formulation
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History of severe autoimmune complications or discontinuation due to toxicity following treatment with an anti-PD-(L)1 pathway therapy.
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Subject has an active autoimmune disease with the exception of auto-immune endocrinopathies that are stable on hormone replacement therapy.
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Subject has a history of colitis.
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History of age-related macular degeneration (AMD).
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Recent surgery, treatment with another investigational agent, active infection, non-healing wound or uncontrolled bleeding/bleeding diathesis.
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Received a vaccine or prior radiotherapy within 14 days prior to Cycle 1 Day 1.
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Prior history of interstitial lung disease that required steroids or ≥ Grade 2 pneumonitis or has current non-infectious pneumonitis or interstitial lung disease.
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Untreated brain metastases or another untreated primary malignancy
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Subject is taking the equivalent of >10 mg/day oral prednisone or on systemic immunosuppressive therapy.
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Subject has had an allogeneic tissue or organ transplantation.
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History of thromboembolic event unless the event occurred > 6 months from Cycle 1 Day 1 and the subject is on anti-coagulation treatment.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | START Midwest | Grand Rapids | Michigan | United States | 49546 |
2 | Providence Cancer Institute | Portland | Oregon | United States | 97213 |
3 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15232 |
4 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
5 | NEXT Oncology | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Palleon Pharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PAL-E602-001