Clinical trial NCT05259696: Glycan Mediated Immune Regulation With a Bi-Sialidase Fusion Protein (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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Oncology
Melanoma
Ovarian Cancer
NSCLC
Non Small Cell Lung Cancer
Colorectal Cancer
Pancreatic Cancer
Cancer
CRC
Colon Cancer
Breast Cancer
Gastric Cancer
EGJ
Esophagogastric Junction Cancer
Head and Neck Cancer
Urothelial Cancer
Bladder Cancer
Keywords: Cancer
Bi-Sialidase
Anti-Tumor
E-602
Cemiplimab
Lead sponsor: Palleon Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-28
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1: The study uses a modified 3+3 design with 5 planned dose levels of E-602 as monotherapy and 2 planned dose levels of E-602 in combination with cemiplimab. Phase 2: Consists of dose-expansion and will use the recommended Phase 2 dose level for E-602 as monotherapy and in combination with cemiplimab.
Primary purpose: TREATMENT

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 cemiplimab.

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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of AEs and SAEs (Phase 1)
timeFrame: 15 Months
measure: Dose-Limiting Toxicities (Phase 1)
timeFrame: 21 days
measure: Objective Response Rate (Phase 2)
timeFrame: 12 Months
measure: Duration of Response (Phase 2)
timeFrame: 16 Months
measure: Progression Free Survival (Phase 2)
timeFrame: 15 Months
measure: Overall Survival (Phase 2)
timeFrame: 15 Months
Secondary outcomes:
measure: Noncompartmental PK Parameters of E-602 (Phase 1)
timeFrame: 12 Months
measure: Noncompartmental PK Parameters of E-602 (Phase 1)
timeFrame: 12 Months
measure: Subjects with Antidrug Antibodies (Phase 1)
timeFrame: 13 Months
measure: Objective Response Rate (Phase 1)
timeFrame: 12 Months
measure: Duration of Response (Phase 1)
timeFrame: 16 Months
measure: Progression Free Survival (Phase 1)
timeFrame: 15 Months
measure: Overall Survival (Phase 1)
timeFrame: 15 Months
measure: Incidence of AEs and SAEs (Phase 2)
timeFrame: 15 Months
measure: Noncompartmental PK Parameters of E-602 (Phase 2)
timeFrame: 12 Months
measure: Noncompartmental PK Parameters of E-602 (Phase 2)
timeFrame: 12 Months
measure: Subjects with Antidrug Antibodies (Phase 2)
timeFrame: 13 Months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Stanford
country: United States
facility: Stanford Health Care
state: California
city: New Haven
country: United States
facility: Yale University Cancer Center
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References: