Imaging immune cells during pre-surgery treatment for melanoma

CD8+ Cell Imaging During Neoadjuvant ImmunoTherapy (The C-IT Neo Trial)

This study is testing if a combination of two immune therapies can shrink tumors in patients with stage III melanoma before surgery and using a special scan to see how their immune cells respond to the treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (other)
• Drugs / interventions: nivolumab, ipilimumab, immunotherapy
• Locations: 4 sites (Basking Ridge, New Jersey and 3 other locations)
• Trial ID: NCT05289193 on ClinicalTrials.gov

What this trial studies

This study investigates the effects of combining nivolumab and ipilimumab as neoadjuvant therapy for patients with stage III melanoma prior to surgical resection. The goal is to determine if this immunotherapy can effectively shrink tumors and reduce the risk of recurrence after surgery. Additionally, the study explores a novel PET scan technique to visualize CD8+ T cells in the immune system and assess its correlation with treatment outcomes. Participants will undergo imaging and treatment to evaluate the efficacy of this approach.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed stage IIIB, IIIC, IIID, or IV melanoma that is amenable to surgical removal.

Not a fit: Patients with melanoma that is not surgically resectable or those with significant comorbidities affecting treatment tolerance may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance treatment strategies for melanoma, potentially leading to better outcomes and reduced recurrence rates after surgery.

How similar studies have performed: Other studies utilizing neoadjuvant immunotherapy for melanoma have shown promising results, indicating potential success for this approach.

Eligibility criteria

Inclusion Criteria:

* Patient is capable of understanding and complying with the protocol requirements and has signed the Informed Consent document.
* Adults at least 18 years of age
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Cytologically or histologically confirmed stage IIIB, IIIC, IIID, or IV melanoma that can be surgically removed.

Notes:

* In-transit melanoma is acceptable.
* Patients can enroll regardless of their BRAF mutational status

  * 1cm of tumor needs to be visible on standard imaging (i.e. FDG PET or CT scan)
  * Screening laboratory values must meet the following criteria:
* WBC ≥ 2.0x109/L
* Neutrophils ≥ 1.5x109/L
* Platelets ≥ 100 x109/L
* Hemoglobin ≥ 5.5 mmol/L
* Creatinine ≤ 1.5x ULN
* AST ≤ 1.5 x ULN and ALT ≤ 1.5 x ULN
* Bilirubin ≤1.5 X ULN

  * Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of study treatment (ipilimumab/nivolumab)
  * Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of ipilimumab + nivolumab
  * Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of study treatment (ipilimumab/nivolumab)

Note: Women who are not of childbearing potential (i.e., who are postmenopausal), or surgically sterile as well as azoospermic men do not require contraception

Exclusion Criteria:

* Subjects with any active autoimmune disease (current symptoms or requirement for immunosuppression at the time of study start).
* Positive active hepatitis B viral infection (+viral load by PCR)
* Prior immunotherapy targeting CTLA-4 and/or PD-1/PD-L1 for any disease.
* Potentially unresectable melanoma.
* History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
* History of severe hypersensitivity reaction to any monoclonal antibody
* Underlying medical conditions that, in the Investigator's opinion, will make the administration of treatment hazardous or obscure the interpretation of toxicity
* Patients who have undergone splenectomy or have other splenic disorders. The normal spleen usually has CD8+ cell activity and serves as a positive control to enable proper imaging technique.
* Use of other investigational drugs before study drug administration 30 days and 5 half-times before study inclusion
* Pregnant or nursing

Where this trial is running

Basking Ridge, New Jersey and 3 other locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (RECRUITING)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (RECRUITING)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (RECRUITING)

Study contacts

• Principal investigator: Michael Postow, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Michael Postow, MD

Conditions: Melanoma, Melanoma Stage III, CD8+ Cell Imaging, C-IT Neo Trial, stage III melanoma, 89Zr-Df-Crefmirlimab, Memorial Sloan Kettering Cancer Center, 21-456