A Multiple Dose, Dose Escalation Trial of AEB1102 in Patients With Advanced Solid Tumors

A Multiple Dose, Dose Escalation Trial of AEB1102 (Co-ArgI-PEG) in Patients With Advanced Solid Tumors

This is the first-in-human study of the safety of increasing dose levels of AEB1102 in patients with advanced cancers. The study will also evaluate the amounts of AEB1102 in blood, the effects of AEB1102 on blood amino acid levels and tumor growth.

Study Overview

• Status: Completed
• Conditions: Advanced Cancers
• Intervention / Treatment: Drug: Co-ArgI-PEG

Detailed Description

In this phase I/2 multiple dose, dose escalation study utilizing a classic 3+3 design. Sequential cohorts of patients will receive AEB1102 IV weekly at one of a series of increasing dose levels. Dose escalation will be dependent on the frequency of specific dose-limiting toxicities in the prior cohort of patients. The study will determine the maximum tolerated dose (MTD) of AEB1102, evaluate the safety profile of the compound, assess the pharmacokinetic profile of AEB1102, determine the effect of AEB1102 on blood arginine levels and evaluate the anti-tumor activity of AEB1102.

Following the determination of the MTD, additional cohorts of patients with uveal, cutaneous melanoma and small cell lung cancer will be enrolled and treated with AEB1102 at the MTD.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85258
      • Pinnacle Research
  • California
    • Los Angeles, California, United States, 90024
      • UCLA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Orange City, Florida, United States, 32763
      • Research Center: Mid Florida Hematology/Oncology Centers
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General
    • Boston, Massachusetts, United States, 02114
      • Dana Farber
  • Missouri
    • Saint Louis, Missouri, United States, 93110
      • Washington University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390-8852
      • UTSW

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

For patients participating in any part of the trial:

• has an advanced solid tumor previously treated with, or inability to tolerate, standard therapy for the disease, or for which a standard therapy does not exist, and as such is considered a candidate for Phase 1 treatment
• has adequate organ function: Hgb ≥9 g/dL; absolute neutrophil count (ANC) ≥ 1.5x109/L; plt ≥ 100,000/μL; AST and ALT < 2.5x ULN (< 5x ULN in patients with liver metastases); total bilirubin < 2.0 mg/dL; serum creatinine ≤ 1.5x ULN
• ECOG performance score 0-2

For patients participating in any expansion group:

• has measurable disease based on RECIST 1.1 as determined by the treating investigator. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
• willing to consent for biopsy is strongly recommended but not mandatory
• recovery of toxicities related to any prior treatments to at least Grade 1 by CTCAE v 4.03. Exceptions are patients with adverse event(s) that are clinically nonsignificant and/or stable on supportive therapy.

For patients participating in specific expansion groups:

Cutaneous Melanoma:

• unresectable, locally advanced or metastatic (AJCC stage IIIB, IIIC, or IV) cutaneous malignant melanoma
• relapsed or progressive disease after or unable to tolerate at least one prior systemic anticancer regimen for metastatic disease involving immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4)
• in tumors with a relevant BRAF mutation, relapsed, refactory, or unable to tolerate at least one prior systemic anticancer regimen for metastic disease involving a BRAF inhibitor

Uveal Melanoma:

• uveal melanoma at metastic stage

Small Cell Lung Cancer:

• extensive disease previously treated with, or inability to tolerate, platinum-based chemotherapy

Exclusion Criteria:

• has primary CNS malignancy
• history of untreated brain mets or leptomeningeal disease or spinal cord compression
• effects of prior anticancer therapy recovered to grade < 2
• known HIV
• active infection
• major surgery within 2 weeks
• history of another malignancy within 2 years prior

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AEB1102 Dose Escalation Cohort 1; 3 patients dosed at 0.01 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 2; 4 patients dosed at 0.02 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 3; 4 patients dosed at 0.04 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 4; 4 patients dosed at 0.08 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 5; 3 patients dosed at 0.12 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 6; 4 patients dosed at 0.18 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 7; 5 patients dosed at 0.27 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 8; 7 patients dosed at 0.40 mg/kg until MTD determined	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Dose Escalation Cohort 9; 7 patients dosed at 0.33 mg/kg until MTD determined MTD determined at 0.33 mg/kg	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102
Experimental: AEB1102 Expansion; Uveal: 11 patients dosed at 0.33 mg/kg Cutaneous Melanoma: 11 dosed at 0.33 mg/kg SCLC: 13 patients dosed at 0.33 mg/kg	Drug: Co-ArgI-PEG; Administered IV; Other Names: AEB1102

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum tolerated dose	the dose level at which no more than 1/6 patients experiences dose-limiting toxicity	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety profile (changes in physical exam, laboratory measures, reported adverse events)	changes in physical exam, laboratory measures, reported adverse events	4 weeks +

Collaborators and Investigators

• Sponsor: Aeglea Biotherapeutics
• Investigators: Study Director: Jim Joffrion, Aeglea BioTherapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): May 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: August 25, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (Estimate): September 28, 2015

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: November 3, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: CAEB1102-100B