Study ADI-PEG 20 Plus Pembrolizumab in Advanced Solid Cancers
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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:
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Outcome Measures
Primary Outcome Measures
- 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 [Up to 36 months]
Number of participants with treatment-related adverse events and severity this is graded by CTCAE and MedDRA for Coding
Secondary Outcome Measures
- Number of Participants with PFS with Combination ADI-PEG 20 and Pembro. [Assessments ever 9 weeks for 12 months]
Progression Free Survival determined by RECIST 1.1
- Number of Participants with RR with Combination ADI-PEG 20 and Pembro. [Assessments ever 9 weeks for 12 months]
Response Rate determined by RECIST 1.1
Other Outcome Measures
- Overall Survival [12 months after end of treatment]
Follow-Up by Phone or Clinic Visit
Eligibility Criteria
Criteria
Select Inclusion Criteria:
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Histologically confirmed diagnosis of advanced solid tumor.
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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.
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Measurable disease using RECIST 1.1 criteria.
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Age ≥ 18 years.
Select Exclusion Criteria:
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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.
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Subjects who had been treated with ADI-PEG 20 previously.
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History of seizure disorder not related to underlying cancer.
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Known allergy to pegylated compounds.
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Known allergy to E. coli drug products (such as GMCSF).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Facility National Cheng Kung University | Tainan | Taiwan | 704 |
Sponsors and Collaborators
- Polaris Group
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- POLARIS2016-002