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

NCT ID: NCT02561234

Last Updated: 2021-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2019-05-31

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.

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.

Conditions

Advanced Cancers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AEB1102 Dose Escalation Cohort 1

3 patients dosed at 0.01 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 2

4 patients dosed at 0.02 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 3

4 patients dosed at 0.04 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 4

4 patients dosed at 0.08 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 5

3 patients dosed at 0.12 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 6

4 patients dosed at 0.18 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 7

5 patients dosed at 0.27 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 8

7 patients dosed at 0.40 mg/kg until MTD determined

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

AEB1102 Dose Escalation Cohort 9

7 patients dosed at 0.33 mg/kg until MTD determined MTD determined at 0.33 mg/kg

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

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

Group Type: EXPERIMENTAL

Co-ArgI-PEG

Intervention Type: DRUG

Administered IV

Interventions

Co-ArgI-PEG

Administered IV

Intervention Type: DRUG

Other Intervention Names

AEB1102

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aeglea Biotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jim Joffrion

Role: STUDY_DIRECTOR

Aeglea Biotherapeutics, Inc.

Locations

Pinnacle Research

Phoenix, Arizona, United States

UCLA

Los Angeles, California, United States

University of Colorado

Aurora, Colorado, United States

Research Center: Mid Florida Hematology/Oncology Centers

Orange City, Florida, United States

Dana Farber

Boston, Massachusetts, United States

Massachusetts General

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Columbia University

New York, New York, United States

Providence Cancer Center

Portland, Oregon, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

UTSW

Dallas, Texas, United States

Countries

Puerto Rico; United States

Other Identifiers

CAEB1102-100B

Identifier Type: -

Identifier Source: org_study_id