Safe Stop Ipilimumab-nivolumab (IPI-NIVO) Trial

Not Applicable

Recruiting

• Conditions: Melanoma Stage IV; Melanoma Stage III; Toxicity, Drug; Immunotherapy
• Interventions: Drug: nivolumab

• Registration Number: NCT05652673
• Lead Sponsor: Erasmus Medical Center

Brief Summary

Safe Stop IPI-NIVO Trial: Early discontinuation of nivolumab upon achieving a (confirmed) complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-12
• Study First Submitted QC: 2022-12-14
• Study First Posted: 2022-12-15
• Study Start: 2023-02-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-02-28
• Primary Completion: 2025-12-01
• Study Completion: 2029-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• 18 years of age or older

• Irresectable stage III or metastatic melanoma

• Treated with at least one dose of first-line ipilimumab-nivolumab and considered to be a candidate for maintenance treatment with nivolumab:

  • previous systemic treatment, including immune-checkpoint inhibitors, in (neo)adjuvant setting for resectable melanoma is allowed
  • in this protocol, nivolumab maintenance is interchangeable with pembrolizumab maintenance therapy.

• Response evaluation according to RECIST v1.1 30 using a diagnostic CT documenting target lesions every 12 (-2/+6) weeks from the start of ipilimumab-nivolumab:

  • for patients with CR on a diagnostic CT at response evaluation, a low-dose CT (which is usually part of 18FDG-PET/CT) is allowed at baseline
  • for patients with PR on a diagnostic CT at response evaluation, a low-dose CT (which is usually part of 18FDG-PET/CT) is allowed if sufficient target lesions are measurable for response evaluation according to RECIST v1.1 criteria 30
  • in case of asymptomatic brain metastases prior to start of first-line ipilimumab-nivolumab, intracerebral tumor response should be confirmed using an MRI for response evaluation prior to inclusion in this study.

• Patients should be included after first CR/PR or first confirmed CR/PR according to RECIST v1.1 30:

  • inclusion should take place no later than 5 weeks after first confirmed CR/PR
  • in case of SD at first response evaluation, confirmed CR/PR is required for inclusion
  • planned and willing to discontinue nivolumab within 4(+1) weeks after inclusion, i.e. first CR/PR or first confirmed CR/PR
  • no later than 9 months after start of treatment with ipilimumab-nivolumab

• Presence of MRI brain for the screening of brain metastases (prior to discontinuation of ipilimumab-nivolumab)

• Participants with previously locally treated brain metastases may participate in case they meet the following criteria:

  • completely asymptomatic brain metastases at inclusion
  • MRI of brain at baseline and for response evaluation during treatment

• Signed and dated informed consent form

Exclusion Criteria

• Patients with SD/PD according to RECIST v1.1

• Malignant disease other than being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to start of study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ.

• Presence of symptomatic brain metastases:

  • prior to first-line treatment with ipilimumab-nivolumab, or;
  • when defined as new or progressive brain metastases at the time of study entry;
  • brain metastases with need for steroid treatment in the last 8 weeks prior to study entry Note: An incidental epileptic seizure caused by a brain lesion is not considered an exclusion criterion.

(provided that the other in- and exclusion criteria are met);

• Presence of leptomeningeal metastases;
• Systemic chronic steroid therapy (>10mg/day prednisone or equivalent) at inclusion or patients who need or needed any other second-line immunosuppressive therapy (e.g. infliximab, mycophenolate mofetil) for the treatment of immune related adverse events (irAEs). Note: local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Early discontinuation of nivolumab	nivolumab	-

Primary Outcome Measures

Name	Time	Method
Ongoing response	12 months after start of ipilimumab-nivolumab combination therapy	The rate of ongoing response at 12 months in patients with irresectable stage III or metastatic melanoma who are treated with first-line ipilimumab-nivolumab and who early discontinue nivolumab upon achieving a CR or PR according to RECIST v1.1

Secondary Outcome Measures

Name	Time	Method
ORR	5 years after inclusion	Overall Response Rate (ORR) per RECIST v1.1 in retreated patients
Re-treatment	5 years after inclusion	Rate of re-treatment for melanoma
Ongoing response	24 months after start of treatment	Ongoing response at 24 months after start of first-line treatment with ipilimumab-nivolumab
Disease control	5 years after inclusion	Disease control (CR/PR) at different time points
duration of response	5 years after inclusion	Duration of response (CR/PR) measured until progressive/recurrent disease
Melanoma Specific Survival rate	5 years after inclusion	Melanoma specific survival measured from start of first-line treatment with ipilimumab-nivolumab until melanoma related death
Overall Survival	5 years after inclusion	Overall survival (OS) measured from start of first-line treatment with ipilimumab-nivolumab until death by any cause
(serious) adverse events	5 years after inclusion	Impact of discontinuation treatment on (S)AEs
Disease control (CR/PR/SD [stable disease]/not PD [progressive disease]) after restarting (systemic) treatment for melanoma	5 years after inclusion	Disease control (CR/PR/SD \[stable disease\]/not PD \[progressive disease\]) after restarting (systemic) treatment for melanoma
Quality of life questionnaires EuroQoL EQ-5D-5	5 years after inclusion	Quality of life is measured using questionnaires: EuroQoL EQ-5D-5

Trial Locations

Locations (1)

Erasmus MC; 🇳🇱 Rotterdam, Netherlands