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

December 22, 2023 updated by: Palleon Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

273

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Principal Investigator:
          • Sandip Patel, MD
        • Contact:
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California
        • Contact:
        • Principal Investigator:
          • Anthony El-Khoueiry, MD
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Health Care
        • Contact:
        • Principal Investigator:
          • Chris Chen, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University Cancer Center
        • Principal Investigator:
          • Mario Sznol, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Justin Gainor, MD
        • Contact:
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • Start Midwest
        • Contact:
        • Principal Investigator:
          • Manish Sharma, MD
    • New York
      • Buffalo, New York, United States, 14263
        • Recruiting
        • Roswell Park Comprehensive Cancer Center
        • Principal Investigator:
          • Igor Puzanov, MD
        • Contact:
      • New York, New York, United States, 10032
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Cancer Institute
        • Principal Investigator:
          • Brendan Curti, MD
        • Contact:
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Medical Center
        • Principal Investigator:
          • Jason Luke, MD
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
        • Contact:
        • Principal Investigator:
          • Melissa Johnson, MD
    • Texas
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • NEXT Oncology
        • Contact:
        • Principal Investigator:
          • Anthony Tolcher, MD
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists
        • Principal Investigator:
          • Alexander I. Spira, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation - Monotherapy

Subjects will receive E-602 as monotherapy.

Planned monotherapy dose levels: 1 mg/kg, 3 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg.
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
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).
Experimental: Dose Escalation - Combination

Subjects will receive E-602 in combination with cemiplimab.

E-602 dose(s): Will be initiated at dose level(s) that have previously completed dosing and DLT assessments as monotherapy.

Cemiplimab dose: 350 mg.
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
Biological: Cemiplimab
Subjects will receive cemiplimab (administered once every 3 weeks, via IV infusion).
Other Names:
  • REGN2810
  • Libtayo
Experimental: Expansion - Combination

Subjects will receive E-602 in combination with cemiplimab.

E-602 dose: Subjects will receive E-602 at the recommended Phase 2 dose determined in Phase 1 in combination with cemiplimab.

Cemiplimab dose: 350 mg.
Biological: E-602
Subjects will receive E-602 (administered weekly, via IV infusion).
Biological: Cemiplimab
Subjects will receive cemiplimab (administered once every 3 weeks, via IV infusion).
Other Names:
  • REGN2810
  • Libtayo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of AEs and SAEs (Phase 1)
Time Frame: 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.
15 Months
Dose-Limiting Toxicities (Phase 1)
Time Frame: 21 days
Incidence of dose-limiting toxicities (DLTs) within a modified 3+3 trial design
21 days
Objective Response Rate (Phase 2)
Time Frame: 12 Months
Objective response rate of confirmed complete response and partial response
12 Months
Duration of Response (Phase 2)
Time Frame: 16 Months
Duration of Response of confirmed complete response or partial response.
16 Months
Progression Free Survival (Phase 2)
Time Frame: 15 Months
Time from first study treatment dose until the first date when progressive disease (PD) is objectively documented or death from any cause
15 Months
Overall Survival (Phase 2)
Time Frame: 15 Months
Time from first study treatment dose until death
15 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Noncompartmental PK Parameters of E-602 (Phase 1)
Time Frame: 12 Months
Maximum plasma concentration (Cmax)
12 Months
Noncompartmental PK Parameters of E-602 (Phase 1)
Time Frame: 12 Months
Area under the plasma concentration-time curve (AUC)
12 Months
Subjects with Antidrug Antibodies (Phase 1)
Time Frame: 13 Months
Number and percentage of subjects who develop detectable antidrug antibodies
13 Months
Objective Response Rate (Phase 1)
Time Frame: 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).
12 Months
Duration of Response (Phase 1)
Time Frame: 16 Months
Duration of Response of confirmed complete response or partial response
16 Months
Progression Free Survival (Phase 1)
Time Frame: 15 Months
Time from first dose to first evidence of radiographically detectable disease or death from any cause
15 Months
Overall Survival (Phase 1)
Time Frame: 15 Months
Time from first study treatment dose until death
15 Months
Incidence of AEs and SAEs (Phase 2)
Time Frame: 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
15 Months
Noncompartmental PK Parameters of E-602 (Phase 2)
Time Frame: 12 Months
Maximum plasma concentration (Cmax)
12 Months
Noncompartmental PK Parameters of E-602 (Phase 2)
Time Frame: 12 Months
Area under the plasma concentration-time curve (AUC)
12 Months
Subjects with Antidrug Antibodies (Phase 2)
Time Frame: 13 Months
Number and percentage of subjects who develop detectable antidrug antibodies
13 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Palleon Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 11, 2022

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

February 11, 2022

First Submitted That Met QC Criteria

February 22, 2022

First Posted (Actual)

February 28, 2022

Study Record Updates

Last Update Posted (Actual)

December 26, 2023

Last Update Submitted That Met QC Criteria

December 22, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PAL-E602-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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