Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response (NIVOPTIMIZE)

Patients with advanced melanoma are, amongst others, currently treated with nivolumab monotherapy or with nivolumab and ipilimumab followed by nivolumab. Even though registration studies administered nivolumab in a 3 mg/kg 2 weekly scheme, currently, nivolumab monotherapy is either administered in a 240 mg 2-weekly scheme or in a 6 mg/kg or 480 mg 4-weekly scheme. With the current dosing regimen, steady-state is achieved after approximately 5 to 6 months, whereas a tumour response is usually observed earlier in patients with metastatic melanoma. Moreover, PD-1 receptor occupancy is almost saturated above doses of 0.3 mg/kg, or at nivolumab serum levels of 10 mg/L, which is a concentration that is achieved after one treatment cycle. In melanoma patients, the additional probability on response in patients treated with 3 mg/kg compared to 1 mg/kg seems limited. PFS and OS for 3 mg/kg were not superior to 1 mg/kg. Therefore, in this study, our aim is to investigate nivolumab trough levels and pharmacokinetic parameters after 3 reduced nivolumab doses.

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Michiel Zietse, MSc; Phone Number: +31642534225; Email: michielzietse@gmail.com

Study Locations

• Netherlands
  • Pending
    • Rotterdam, Pending, Netherlands
      • Recruiting
      • Erasmus MC
      • Contact: Michiel MC; Email: m.zietse@erasmusmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Advanced or metastatic melanoma
• Current treatment with nivolumab for advanced or metastatic melanoma, in a 6 mg/kg or 480 mg, 4 weekly scheme
• Documented confirmed and ongoing CR, PR or SD according to RECIST v1.1
• On treatment for at least 6 months

Exclusion Criteria:

• Unable to draw blood for study purposes
• Patients willing to participate or already included in the SAFE-STOP trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab; Patients in the experimental arm receive three reduced nivolumab doses of 240 mg Q4W	Drug: Nivolumab; Participants receive three reduced doses of 240 mg every four weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the nivolumab mean trough level after 3 reduced doses (240 mg every 4 weeks) and after the first dose of 6 mg/kg or 480 mg.	Difference between the nivolumab mean trough level after 3 reduced doses (240 mg every 4 weeks) and after the first dose of 6 mg/kg or 480 mg.	Through study completion, an average of four months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses	- PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses	Through study completion, an average of four months
Grade ≥3 adverse events (CTCAE) during reduced doses	Grade ≥3 adverse events (CTCAE) during reduced doses	Through study completion, an average of four months
Number of patients with new PD during 3 reduced doses	Number of patients with new PD during 3 reduced doses	Through study completion, an average of four months

Collaborators and Investigators

• Sponsor: Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: October 4, 2023
• First Submitted That Met QC Criteria: October 30, 2023
• First Posted (Actual): November 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: NL77343.078.21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No