Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03922880

Collaborator

(none)

Enrollment

Location

Arm

47.5

Anticipated Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is measuring the safety of the study drug, ADI-PEG 20, combined with immunotherapy drugs nivolumab and ipilimumab in treating patients with advanced uveal melanoma.

Condition or Disease	Intervention/Treatment	Phase
Uveal Melanoma	Drug: ADI PEG20 Drug: Nivolumab Drug: Ipilimumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

9 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study Combining Arginine Depletion and Checkpoint Inhibition in Uveal Melanomas

Actual Study Start Date :

Apr 16, 2019

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Advanced Uveal Melanoma	Drug: ADI PEG20 ADI-PEG 20 will be administered at a dose of 36mg/m2 intramuscularly once a week. Drug: Nivolumab Nivolumab 240mg + Ipilimumab 1mg/kg for up to 8 total doses of ipilimumab. One ipilimumab has completed, nivolumab 480mg will be given every 4 weeks. Drug: Ipilimumab Ipilimumab 1mg/kg with Nivolumab 240mg for up to 8 total doses of ipilimumab. The first four doses of ipilimumab will be scheduled once every 3 weeks. The 5th-8th doses of ipilimumab will be scheduled once every 6 weeks with nivoumab 240mg every 3 weeks.

Arm

Intervention/Treatment

Experimental: Advanced Uveal Melanoma

Drug: ADI PEG20

ADI-PEG 20 will be administered at a dose of 36mg/m2 intramuscularly once a week.

Drug: Nivolumab

Nivolumab 240mg + Ipilimumab 1mg/kg for up to 8 total doses of ipilimumab. One ipilimumab has completed, nivolumab 480mg will be given every 4 weeks.

Drug: Ipilimumab

Ipilimumab 1mg/kg with Nivolumab 240mg for up to 8 total doses of ipilimumab. The first four doses of ipilimumab will be scheduled once every 3 weeks. The 5th-8th doses of ipilimumab will be scheduled once every 6 weeks with nivoumab 240mg every 3 weeks.

Outcome Measures

Primary Outcome Measures

Safety as assessed by CTCAE version 5.0 [Up to 3 years]

Secondary Outcome Measures

Objective Response Rate by RECIST 1.1 [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Advanced or unresectable melanoma of presumed uveal origin. Non-uveal melanomas with "malignant blue nevus" physiology with GNAQ, GNA11, CYSLTR2, or PLCB4 driver alterations are eligible upon discussion with the Principal Investigator.
Disease must be measurable according to RECIST 1.1. Disease that has undergone local therapy in the past 30 days is not considered measurable unless the investigator has documented progression despite the local therapy.
Disease must be amenable to a biopsy attempt, in the opinion of the investigator.
Asymptomatic untreated brain metastases are allowed. Symptomatic brain metastases that have undergone local therapy with RT or surgery and have not required an increase in steroid dose in prior 2 weeks are allowed.

Note: Seizure prophylaxis with untreated brain metastases are allowed.

Patients must have an Easter Cooperative Oncology Group (ECOG) Performance Statue (PS) of 0-1.
Acceptable liver, renal, and hematological function:
Total bilirubin </= 1.5x upper limit of normal (ULN); patients with Gilbert's Syndrome must have bilirubin </= 3x ULN
Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) </= 3 x ULN (</= 5x if liver metastases are present)
Estimated glomerular filtration rate (GFR) >/= 30 mL/min using a cancer-specific GFR

Model; the calculator found at:

http://tavarelab.cruk.com.ac.uk/JanowitzWilliamsGFR/

Hemoglobin >/= 9 g/dL
Neutrophils >/= 1.5 x 10^9/L
Platelets >/= 100 x 10^9/L
Female patients of childbearing potential and their partners (if male) and male patients with female partners of childbearing potential and their partners must agree to use a highly effective form of contraception for the duration of the study from the list below or agree to refrain from intercourse for the duration of the trial and for at least 30 days after the last administration of ADI-PEG20 and at least 150 days (if female) or 210 days (if male) after the final dose of ipilimumab and/or nivolumab whichever is later. Highly effective forms of contraception include the following:
combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal)
progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
intrauterine device
intrauterine hormone-releasing system
bilateral tubal occlusion
vasectomized partner

Exclusion Criteria:

Other active malignancy that in the opinion of the treating investigator will interfere with the assessments of efficacy for uveal melanoma in this study
History of seizure disorder not related to malignancy
Pregnancy or lactation
Expected non-adherence to protocol
Known allergy to E. coli drug products (such as GM-CSF)
Known allergy to pegylated compounds
Prior treatment with ADI-PEG20 or another experimental arginine deprivation strategy
Systemic anticancer therapy within 3 weeks or 1 cycle length, whichever is shorter, of first day of planned study therapy
Presence of treatment-related adverse events that have not recovered or stabilized at Grade 1 (excepting vitiligo and alopecia or treated endocrine conditions). AEs that are Grade 2 that are not felt to be a significant safety risk (e.g. rash, asymptomatic thyroiditis) may be allowable upon discussion with the Principal Investigator.
Active autoimmune disease or any condition requiring greater than 10mg prednisone per day equivalent or other immune suppressive medication (e.g. anti-TNF agents) within 14 days of study screening. Inhaled or topical steroids and adrenal replacements does of steroids >10mg prednisone are allowed in the absence of active autoimmune disease.
History of myocarditis or motor neuropathy of any grade
Gout flares within the past 28 days or sequelae of chronic gout, such as gouty arthritis, are excluded.

Note: Patients with asymptomatic hyperuricemia without arthralgias or arthritic symptoms are eligible, as are patients with known gout on chronic uric acid lowering medication who have not experienced a flare within 28 days