A Late Phase Randomized Open-Label Multi Cohort Trial to Evaluate irAEs With Different Standard of Care Dosing Strategies of Standard of Care Immunotherapies
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 192
- Locations
- 1
- Primary Endpoint
- Proportions of grade ≥3 immune related adverse events (irAEs) between the two arms in each cohort
Study Overview
Brief Summary
Phase 3/4 open label, randomized two cohort study (2 arms in each cohort).
It is hypothesized that for people with a histologically or cytologically confirmed diagnosis of malignancy, the higher dose immunotherapy (every 6 weeks Pembrolizumab 400mg dose and every 4 weeks Nivolumab 480mg dose) has more immune-related adverse events irAEs compared to lower dose (every 3 weeks Pembrolizumab 200mg dose and every 2 weeks Nivolumab 240mg dose).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Ability of participant to understand this study, and participant willingness to sign a written informed consent.
- •Males and females age ≥ 18 years
- •ECOG Performance Status (PS) 0 - 2 (Appendix A.)
- •Females of childbearing potential must have a negative urine pregnancy test 72 hours prior to initiating treatment.
- •Histologically or cytologically confirmed diagnosis of solid tumor malignancy
- •Eligible to receive pembrolizumab or nivolumab based therapy
- •Any disease setting (neoadjuvant, adjuvant, unresectable, metastatic) or any line of therapy is allowed. NOTE: Standard of care combination agents(chemotherapy, targeted therapy, biologics) are allowed because irAEs are the primary objective
- •Adequate organ function, defined as follows:
- •Leukocytes (White Blood Cell [WBC]) >1.0 K/UL Absolute Neutrophil Count >1.0 K/UL Platelets > 50 K/UL Hemoglobin ≥ 7 g/dL Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation Total bilirubin ≤ 1.5 x ULN Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN
Exclusion Criteria
- •Simultaneously enrolled in any therapeutic clinical trial
- •Concurrent or planned use of other immunotherapies or radiation
- •Has not recovered from irAEs due to prior immunotherapy treatment (>=grade 2 is considered not recovered). Conditions that meet grade 2 criteria but are considered clinically stable at the discretion of the investigator will be allowed.
- •Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
- •Currently pregnant or breastfeeding
- •Has a known allergic reaction to any excipient contained in the study drug formulation
- •Active Grade 3 (per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 ) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment.
Arms & Interventions
Arm 1
Pembrolizumab Cohort- Dose: 200 mg Route: IV Schedule: Once every 3 weeks Overall Treatment Duration per Participation: Average of 12 months Cycle Length: Per SOC (3 weeks)
Nivolumab Cohort- Dose: 240 mg Route: IV Schedule: Once every 2 weeks Overall Treatment Duration per Participation: Average of 12 months Cycle Length: Per SOC (2 weeks)
Intervention: Pembrolizumab (Drug)
Arm 2
Nivolumab Cohort- Dose: 480 mg Route: IV Schedule: Once every 4 weeks Overall Treatment Duration per Participant: Average of 12 months Cycle length: Per SOC (4 weeks)
Pembrolizumab Cohort- Dose: 400 mg Route: IV Schedule: Once every 6 weeks Overall Treatment Duration per Participant: Average of 12 months Cycle length: Per SOC (6 weeks)
Intervention: Nivolumab (Drug)
Arm 2
Nivolumab Cohort- Dose: 480 mg Route: IV Schedule: Once every 4 weeks Overall Treatment Duration per Participant: Average of 12 months Cycle length: Per SOC (4 weeks)
Pembrolizumab Cohort- Dose: 400 mg Route: IV Schedule: Once every 6 weeks Overall Treatment Duration per Participant: Average of 12 months Cycle length: Per SOC (6 weeks)
Intervention: Pembrolizumab (Drug)
Arm 1
Pembrolizumab Cohort- Dose: 200 mg Route: IV Schedule: Once every 3 weeks Overall Treatment Duration per Participation: Average of 12 months Cycle Length: Per SOC (3 weeks)
Nivolumab Cohort- Dose: 240 mg Route: IV Schedule: Once every 2 weeks Overall Treatment Duration per Participation: Average of 12 months Cycle Length: Per SOC (2 weeks)
Intervention: Nivolumab (Drug)
Outcomes
Primary Outcomes
Proportions of grade ≥3 immune related adverse events (irAEs) between the two arms in each cohort
Time Frame: 12 weeks
Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
Proportions of grade ≥3 immune related adverse events (irAEs) between the two arms in each cohort
Time Frame: 12 weeks
Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
Secondary Outcomes
- All grades of immune related adverse events (irAEs)(Start of treatment to EOT. Approximate time frame 6-12 months.)
- Time to resolution of immune related adverse events (irAEs)(Start of treatment to end of follow up. Approximate Time Frame: 2-3 Years)
- Time of treatment discontinuation due to immune related adverse events (irAEs)(Start of treatment to discontinuation Approximate Time Frame: 12 Months)
- Overall Response Rate (ORR)(Approximate time frame: 12 weeks)
- All grades of immune related adverse events (irAEs)(Start of treatment to EOT. Approximate time frame 6-12 months.)
- Overall Response Rate (ORR)(Approximate time frame: 12 weeks)
- Time to resolution of immune related adverse events (irAEs)(Start of treatment to end of follow up. Approximate Time Frame: 2-3 Years)
- Time of treatment discontinuation due to immune related adverse events (irAEs)(Start of treatment to discontinuation Approximate Time Frame: 12 Months)
- Disease-Free Survival (DFS)(6 months, 1 year, and 2 yearsApproximate time frame 3 years.)
- Progression-Free Survival (PFS)(6 months, 1 year, and 2 yearsApproximate time frame 3 years.)
- Overall Survival (OS)(Approximate time frame: 2 years)
Investigators
Anup Kasi
Associate Professor
University of Kansas Medical Center