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

• ClinicalTrials.gov Identifier: NCT02561234
• Recruitment Status: Completed
• First Posted: September 28, 2015
• Last Update Posted: October 14, 2019
• Sponsor: Aeglea Biotherapeutics
• Information provided by (Responsible Party): Aeglea Biotherapeutics

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Cancers	Drug: Co-ArgI-PEG	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multiple Dose, Dose Escalation Trial of AEB1102 (Co-ArgI-PEG) in Patients With Advanced Solid Tumors
• Study Start Date: October 2015
• Actual Primary Completion Date: May 2019
• Actual Study Completion Date: May 2019

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: AEB1102

Outcome Measures

Primary Outcome Measures :

1. maximum tolerated dose [ Time Frame: 4 weeks ]
   the dose level at which no more than 1/6 patients experiences dose-limiting toxicity

Secondary Outcome Measures :

1. safety profile (changes in physical exam, laboratory measures, reported adverse events) [ Time Frame: 4 weeks + ]
   changes in physical exam, laboratory measures, reported adverse events

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Pinnacle Research

Phoenix, Arizona, United States, 85258

United States, California

UCLA

Los Angeles, California, United States, 90024

United States, Colorado

University of Colorado

Aurora, Colorado, United States, 80045

United States, Florida

Research Center: Mid Florida Hematology/Oncology Centers

Orange City, Florida, United States, 32763

United States, Massachusetts

Dana Farber

Boston, Massachusetts, United States, 02114

Massachusetts General

Boston, Massachusetts, United States, 02114

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 93110

United States, New York

Columbia University

New York, New York, United States, 10032

United States, Oregon

Providence Cancer Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15232

United States, Texas

UTSW

Dallas, Texas, United States, 75390-8852

Sponsors and Collaborators

Aeglea Biotherapeutics

Investigators

• Study Director: Jim Joffrion; Aeglea Biotherapeutics, Inc.

More Information

• Responsible Party: Aeglea Biotherapeutics
• ClinicalTrials.gov Identifier: NCT02561234
• Other Study ID Numbers: CAEB1102-100B
• First Posted: September 28, 2015
• Last Update Posted: October 14, 2019
• Last Verified: October 2019