Trial to Evaluate irAEs With Different Standard of Care Dosing Strategies of Standard of Care Immunotherapies

University of Kansas

Status and phase: Begins enrollment this month; Phase 3

Conditions: Solid Tumor Malignancies

Treatments: Drug: Nivolumab; Drug: Pembrolizumab

Study type: Interventional

Funder types: Other

Identifiers

NCT07174453

STUDY00161901

Details and patient eligibility

About

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).

Enrollment: 192 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Ability of participant to understand this study, and participant willingness to sign a written informed consent.
2. Males and females age ≥ 18 years
3. ECOG Performance Status (PS) 0 - 2 (Appendix A.)
4. Females of childbearing potential must have a negative urine pregnancy test 72 hours prior to initiating treatment.
5. Histologically or cytologically confirmed diagnosis of solid tumor malignancy
6. Eligible to receive pembrolizumab or nivolumab based therapy
7. 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
8. 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

1. Simultaneously enrolled in any therapeutic clinical trial
2. Concurrent or planned use of other immunotherapies or radiation
3. 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.
4. Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
5. Currently pregnant or breastfeeding
6. Has a known allergic reaction to any excipient contained in the study drug formulation
7. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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192 participants in 2 patient groups

Arm 1

Experimental group

Description:

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)

Treatment:

Drug: Pembrolizumab

Drug: Nivolumab

Arm 2

Experimental group

Description:

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)

Treatment:

Drug: Pembrolizumab

Drug: Nivolumab