Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (GLIMMER-01)

Breast Cancer Clinical Trial

— GLIMMER-01  

Official title:

A Phase 1/2, Open-Label, Single-Arm, Dose-Escalation and Dose-Expansion Study of the Safety, Tolerability, Pharmacokinetic, and Antitumor Activity of E-602 as a Single Agent and in Combination With Cemiplimab in Patients With Advanced Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05259696
• Other study ID #: PAL-E602-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 11, 2022
• Est. completion date: June 2025

Study information

• Verified date: December 2023
• Source: Palleon Pharmaceuticals, Inc.
• Contact: Palleon Clinical
• Phone: 857-285-5900
• Email: clinical[@]palleonpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 cemiplimab.

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 cemiplimab. 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 cemiplimab.

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 camiplimab. 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 273 subjects (up to 87 in Phase 1 and up to 186 in Phase 2). Subjects will participate in the study for about 16 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 273
• Est. completion date: June 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. 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.

a. 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).

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

3. Subject has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

4. Adequate bone marrow, coagulation, renal function, and liver function as determined by laboratory tests

Key Exclusion Criteria:

1. For cohorts receiving E-602 and cemiplimab combination therapy:

1. Prior moderate or severe hypersensitivity to cemiplimab or its formulation

2. History of severe (= Grade 3) autoimmune complications or discontinuation due to toxicity following treatment with an anti-PD-(L)1 pathway therapy as a monotherapy, with the exception of asymptomatic Grade 3 elevations in lipase and/or amylase not associated with clinical manifestations of pancreatitis.

3. Subject has an active autoimmune disease. The following are not exclusionary:

vitiligo, type 1 diabetes, autoimmune endocrinopathies that are stable on hormone replacement therapy, or psoriasis that does not require systemic treatment.

4. Previously received idelalisib.

2. History of age-related macular degeneration (AMD).

3. Recent surgery, treatment with another investigational agent, active infection, non-healing wound or uncontrolled bleeding/bleeding diathesis.

4. Received a vaccine or prior radiotherapy within 14 days prior to Cycle 1 Day 1.

5. Prior history of interstitial lung disease that required steroids or = Grade 2 immune-related pneumonitis or has current non-infectious pneumonitis or interstitial lung disease. Subject has a history of =Grade 3 radiation pneumonitis, or Grade 2 radiation pneumonitis that has been active within the last 6 months.

6. Untreated brain metastases.

7. A known primary malignancy that is progressing or has required active treatment within the past 3 years.

8. Subject is taking the equivalent of >10 mg/day oral prednisone or on systemic immunosuppressive therapy.

9. Subject has had an allogeneic tissue or organ transplantation.

10. History of thromboembolic event unless the event occurred > 6 months from Cycle 1 Day 1 and the subject is on anti-coagulation treatment.

Related Conditions & MeSH terms

• Bladder Cancer
• Breast Cancer
• Cancer
• Colon Cancer
• Colorectal Cancer
• CRC
• Esophagogastric Junction Cancer
• Gastric Cancer
• Head and Neck Cancer
• Melanoma
• Non Small Cell Lung Cancer
• NSCLC
• Oncology
• Ovarian Cancer
• Pancreatic Cancer
• Urothelial Cancer

Intervention

Biological:
• E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
• Cemiplimab
Subjects will receive cemiplimab (administered once every 3 weeks, via IV infusion).

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Comprehensive Cancer Center	Buffalo	New York
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	University of Southern California	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University Cancer Center	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Providence Cancer Institute	Portland	Oregon
United States	NEXT Oncology	San Antonio	Texas
United States	Stanford Health Care	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Palleon Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of AEs and SAEs (Phase 1)	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.	15 Months
Primary	Dose-Limiting Toxicities (Phase 1)	Incidence of dose-limiting toxicities (DLTs) within a modified 3+3 trial design	21 days
Primary	Objective Response Rate (Phase 2)	Objective response rate of confirmed complete response and partial response	12 Months
Primary	Duration of Response (Phase 2)	Duration of Response of confirmed complete response or partial response.	16 Months
Primary	Progression Free Survival (Phase 2)	Time from first study treatment dose until the first date when progressive disease (PD) is objectively documented or death from any cause	15 Months
Primary	Overall Survival (Phase 2)	Time from first study treatment dose until death	15 Months
Secondary	Noncompartmental PK Parameters of E-602 (Phase 1)	Maximum plasma concentration (Cmax)	12 Months
Secondary	Noncompartmental PK Parameters of E-602 (Phase 1)	Area under the plasma concentration-time curve (AUC)	12 Months
Secondary	Subjects with Antidrug Antibodies (Phase 1)	Number and percentage of subjects who develop detectable antidrug antibodies	13 Months
Secondary	Objective Response Rate (Phase 1)	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).	12 Months
Secondary	Duration of Response (Phase 1)	Duration of Response of confirmed complete response or partial response	16 Months
Secondary	Progression Free Survival (Phase 1)	Time from first dose to first evidence of radiographically detectable disease or death from any cause	15 Months
Secondary	Overall Survival (Phase 1)	Time from first study treatment dose until death	15 Months
Secondary	Incidence of AEs and SAEs (Phase 2)	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	15 Months
Secondary	Noncompartmental PK Parameters of E-602 (Phase 2)	Maximum plasma concentration (Cmax)	12 Months
Secondary	Noncompartmental PK Parameters of E-602 (Phase 2)	Area under the plasma concentration-time curve (AUC)	12 Months
Secondary	Subjects with Antidrug Antibodies (Phase 2)	Number and percentage of subjects who develop detectable antidrug antibodies	13 Months