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

Sponsor
Palleon Pharmaceuticals, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05259696
Collaborator
(none)
267
Enrollment
3
Locations
4
Arms
39.6
Anticipated Duration (Months)
89
Patients Per Site
2.2
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
  • Biological: E-602
  • Biological: Pembrolizumab
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 3+3 methodology. Any Phase 1 cohort may be backfilled, up to a total of 15 subjects to obtain additional safety and PK data at a particular dose level. Phase 1 will enroll subjects with melanoma, ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, or pancreatic 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, or pancreatic) 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

Study Type:
Interventional
Anticipated Enrollment :
267 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Phase 1: The study uses a 3+3 methodology with 4 planned dose levels of E-602 as monotherapy and 2 planned dose levels of E-602 in combination with pembrolizumab. Phase 2: Consists of dose-expansion and will use the recommended Phase 2 dose level for E-602 as monotherapy and in combination with pembrolizumab.Phase 1: The study uses a 3+3 methodology with 4 planned dose levels of E-602 as monotherapy and 2 planned dose levels of E-602 in combination with pembrolizumab. Phase 2: Consists of dose-expansion and will use the recommended Phase 2 dose level for E-602 as monotherapy and in combination with pembrolizumab.
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Pembrolizumab in Patients With Advanced Cancers
Actual Study Start Date :
Feb 11, 2022
Anticipated Primary Completion Date :
Jun 1, 2025
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

ArmIntervention/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, and 20 mg/kg.

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 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:
  • Keytruda
  • MK-3475
  • 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: 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:
  • Keytruda
  • MK-3475
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. Dose-Limiting Toxicities (Phase 1) [21 days]

      Incidence of dose-limiting toxicities (DLTs) within a 3+3 trial design

    3. Immune-Related Toxicities (Phase 1) [15 Months]

      Incidence of immune-related toxicities

    4. Objective Response Rate (Phase 2) [12 Months]

      Objective response rate of confirmed complete response and partial response

    5. Duration of Response (Phase 2) [16 Months]

      Duration of Response of confirmed complete response or partial response.

    6. 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

    7. Overall Survival (Phase 2) [15 Months]

      Time from first study treatment dose until death

    Secondary Outcome Measures

    1. Noncompartmental PK Parameters of E-602 (Phase 1) [12 Months]

      Maximum plasma concentration (Cmax)

    2. Noncompartmental PK Parameters of E-602 (Phase 1) [12 Months]

      Area under the plasma concentration-time curve (AUC)

    3. Subjects with Antidrug Antibodies (Phase 1) [13 Months]

      Number and percentage of subjects who develop detectable antidrug antibodies

    4. 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).

    5. Duration of Response (Phase 1) [16 Months]

      Duration of Response of confirmed complete response or partial response

    6. Progression Free Survival (Phase 1) [15 Months]

      Time from first dose to first evidence of radiographically detectable disease or death from any cause

    7. Overall Survival (Phase 1) [15 Months]

      Time from first study treatment dose until death

    8. 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

    9. Immune-Related Toxicities (Phase 2) [16 Months]

      Incidence of immune-related toxicities

    10. Noncompartmental PK Parameters of E-602 (Phase 2) [12 Months]

      Maximum plasma concentration (Cmax)

    11. Noncompartmental PK Parameters of E-602 (Phase 2) [12 Months]

      Area under the plasma concentration-time curve (AUC)

    12. Subjects with Antidrug Antibodies (Phase 2) [13 Months]

      Number and percentage of subjects who develop detectable antidrug antibodies

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    1. Subjects with advanced or relapsed/refractory melanoma, ovarian cancer, NSCLC, colorectal cancer, or pancreatic cancer who have failed prior therapies.
    1. Subjects with melanoma or NSCLC must have had prior anti-PD-1 pathway therapy and been deemed resistant (had progression on therapy or within 3 months of discontinuation of therapy).
    1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

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

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

    Key Exclusion Criteria:
    1. For cohorts receiving E-602 and pembrolizumab combination therapy:

    2. Prior moderate or severe hypersensitivity to pembrolizumab or its formulation

    3. History of severe autoimmune complications or discontinuation due to toxicity following treatment with an anti-PD-1 pathway therapy.

    4. Subject has an active autoimmune disease with the exception of auto-immune endocrinopathies that are stable on hormone replacement therapy.

    5. Subject has a history of colitis.

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

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

    8. Received a vaccine within 14 days prior to Cycle 1 Day 1.

    9. Prior history of ≥ Grade 2 pneumonitis.

    10. Untreated brain metastases or another untreated primary malignancy

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

    12. Subject has had an organ transplantation.

    13. History of thromboembolic event unless the event occurred > 6 months from start of study treatment and the subject is on anti-coagulation treatment.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1START MidwestGrand RapidsMichiganUnited States49546
    2Sarah Cannon Research InstituteNashvilleTennesseeUnited States37203
    3NEXT OncologySan AntonioTexasUnited States78229

    Sponsors and Collaborators

    • Palleon Pharmaceuticals, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Palleon Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT05259696
    Other Study ID Numbers:
    • PAL-E602-001
    First Posted:
    Feb 28, 2022
    Last Update Posted:
    Apr 8, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Palleon Pharmaceuticals, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 8, 2022