Comparing immune side effects of higher versus lower dosing schedules of pembrolizumab and nivolumab for solid tumors

A Late Phase Randomized Open-Label Multi Cohort Trial to Evaluate irAEs With Different Standard of Care Dosing Strategies of Standard of Care Immunotherapies

This trial will test whether higher-dose, less-frequent pembrolizumab or nivolumab causes more immune-related side effects than lower-dose, more-frequent dosing in adults with solid tumors.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 192 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Kansas Medical Center (Academic / other)
• Drugs / interventions: pembrolizumab, nivolumab, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Westwood, Kansas)
• Trial ID: NCT07174453 on ClinicalTrials.gov

What this trial studies

This is an open-label, randomized Phase 3/4 study with two cohorts, each containing two dosing arms, comparing higher less-frequent versus lower more-frequent standard dosing of pembrolizumab and nivolumab. The primary focus is on immune-related adverse events (irAEs) while allowing standard-of-care combination agents and any disease setting or line of therapy. Adults with histologically or cytologically confirmed solid tumors who are eligible for these PD‑1 inhibitors and have adequate organ function and ECOG 0–2 can enroll. The design aims to directly compare safety profiles of the different standard dosing strategies.

Who should consider this trial

Good fit: Adults (≥18) with a histologically or cytologically confirmed solid tumor who are eligible for pembrolizumab or nivolumab, have ECOG performance status 0–2, and adequate organ function are ideal candidates.

Not a fit: Patients with hematologic malignancies, those ineligible for PD‑1 inhibitors, or those with poor organ function or contraindications to immunotherapy are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the results could identify dosing schedules that reduce immune-related side effects or clinic visits while maintaining effective treatment.

How similar studies have performed: Alternative dosing schedules for pembrolizumab and nivolumab have been used and supported by prior work, but randomized comparisons specifically focused on differences in irAE rates are limited.

Eligibility criteria

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.

Where this trial is running

Westwood, Kansas

• The University of Kansas Cancer Center — Westwood, Kansas, United States (Recruiting)

Study contacts

• Principal investigator: Anup Kasi, MD — University of Kansas Medical Center
• Study coordinator: Cathey Belcher

Conditions Solid Tumor Malignancies; Immunotherapy