Study ADI-PEG 20 Plus Pembrolizumab in Advanced Solid Cancers

Phase 1B Study of ADI-PEG 20 Plus Pembrolizumab in Advanced Solid Cancers

This is a phase 1b, open label trial of ADI-PEG 20 (36 mg/m2) weekly in combination with pembrolizumab (1 and 2 mg/kg or 200 mg) every three weeks. Assessment of safety and tolerability of drug combination

Study Overview

• Status: Terminated
• Conditions: Advanced Solid Cancers
• Intervention / Treatment: Drug: ADI PEG20; Drug: Pembrolizumab

Detailed Description

This is an open-label, phase 1b trial of ADI-PEG 20 in combination with pembrolizumab in subjects with advanced cancers. Dose escalation will occur using a 3 + 3 + 3 design.

The first subject in a dose escalation cohort must have had treatment with ADI-PEG 20 + pembrolizumab with a week of follow up) before the next 2 subjects are enrolled. Thus subjects 2 and 3 may be enrolled on day 8 if there is no dose limiting toxicity (DLT) in subject 1. No additional delay is required between treating subjects 4 to 6 or 7 to 9 in an expanded cohort. Before proceeding to the next cohort dose level, the first 3 eligible subjects in each cohort will have received at least 21 days of treatment (i.e. at least 2 of the expected 3 doses of ADI-PEG 20 + one dose of pembrolizumab).

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan, 704
    • Facility National Cheng Kung University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Select Inclusion Criteria:

1. Histologically confirmed diagnosis of advanced solid tumor.
2. Prior failure of a systemic treatment approved by the health authority in the country where the study will be enrolling. Such subjects may also have been treated with radiotherapy, local therapy or surgery.
3. Measurable disease using RECIST 1.1 criteria.
4. Age ≥ 18 years.

Select Exclusion Criteria:

1. Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
2. Subjects who had been treated with ADI-PEG 20 previously.
3. History of seizure disorder not related to underlying cancer.
4. Known allergy to pegylated compounds.
5. Known allergy to E. coli drug products (such as GMCSF).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADI-PEG 20; This is a phase 1b, open label trial of ADI-PEG 20 (36 mg/m2) weekly in combination with pembrolizumab (1 and 2 mg/kg or 200 mg) every three weeks.	Drug: ADI PEG20; ADI is a recombinant protein cloned from M. hominis and produced in E. coli, and conjugated with PEG of 20,000 mw. Thus ADI-PEG 20 is an arginine degrading enzyme, ADI, coupled to PEG.; Drug: Pembrolizumab; Pembrolizumab is a PD-1 blocking antibody indicated in the USA for the treatment.; Other Names: Keytruda®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events as a Measure of Safety and Tolerability of ADI-PEG 20 in combination with Pembrolizumab in Advanced Solid Cancers	Number of participants with treatment-related adverse events and severity this is graded by CTCAE and MedDRA for Coding	Up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with PFS with Combination ADI-PEG 20 and Pembro.	Progression Free Survival determined by RECIST 1.1	Assessments ever 9 weeks for 12 months
Number of Participants with RR with Combination ADI-PEG 20 and Pembro.	Response Rate determined by RECIST 1.1	Assessments ever 9 weeks for 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Follow-Up by Phone or Clinic Visit	12 months after end of treatment

Collaborators and Investigators

• Sponsor: Polaris Group

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2017
• Primary Completion (Actual): May 7, 2019
• Study Completion (Actual): February 25, 2020

Study Registration Dates

• First Submitted: December 23, 2016
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 18, 2017

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: POLARIS2016-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No