Stopping nivolumab early for melanoma treatment

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

This study is testing if stopping nivolumab early is safe and effective for patients with advanced melanoma who have responded well to their initial treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Erasmus Medical Center (Academic / other)
• Drugs / interventions: ipilimumab, nivolumab, pembrolizumab, infliximab, prednisone
• Locations: 1 site (Rotterdam)
• Trial ID: NCT05652673 on ClinicalTrials.gov

What this trial studies

This trial investigates the early discontinuation of nivolumab in patients with irresectable stage III or metastatic melanoma who have achieved a confirmed complete or partial response after receiving first-line treatment with ipilimumab-nivolumab. The approach aims to evaluate the safety and efficacy of stopping nivolumab treatment early while monitoring patient responses through regular imaging assessments. Participants will undergo response evaluations using diagnostic CT scans to determine their eligibility for maintenance treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with irresectable stage III or metastatic melanoma who have responded to first-line ipilimumab-nivolumab treatment.

Not a fit: Patients who have not received ipilimumab-nivolumab or those with resectable melanoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could reduce unnecessary treatment exposure and associated side effects for patients with melanoma.

How similar studies have performed: While this specific approach is novel, similar studies exploring early treatment discontinuation in immunotherapy have shown promising results.

Eligibility criteria

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

Where this trial is running

Rotterdam

• Erasmus MC — Rotterdam, Netherlands (Recruiting)

Conditions Melanoma Stage IV; Melanoma Stage III; Immunotherapy; Toxicity, Drug