Single dose of neoadjuvant ipilimumab and nivolumab in resectable melanoma with CD8+ cell imaging: Interim results of the C-IT Neo trial.
Year: 2025
Type: conference-abstract
Abstract: 9513 Background: Neoadjuvant (neoadj) immune checkpoint blockade (ICB) is standard of care for patients (pts) with resectable stage III/IV melanoma. A single ICB dose induces substantial peripheral immune activation and 1 dose of neoadj pembrolizumab has promising activity. The efficacy of 1 dose of combination ICB is unknown and clinically important to describe given the toxicity of sequential combination ICB. Methods: In this phase II single-arm trial, pts with resectable stage IIIB-IV melanoma received 1 dose of neoadj nivolumab (nivo) 1mg/kg and ipilimumab (ipi) 3mg/kg 4 weeks prior to resection. The primary endpoint is major pathologic response (MPR), defined as pathologic complete response (pCR) or near CR (≤10% viable tumor). Using a Simon minimax two-stage design, MPR < 30% is deemed not promising and > 50% promising; positive if >12 MPR in 28 pts. Secondary endpoints were response rate (RECIST 1.1), recurrence free survival (RFS), and safety. CD8-PET imaging was done pre-ICB and pre-surgery, using 89 Zr-radiolabeled crefmirlimab to evaluate association with MPR. Autoradiography and CD8 cell infiltrate by IHC were used to verify the on-target binding of crefmirlimab in surgical specimens. Results: Stage I successfully met the interim efficacy threshold with 5 of 12 pts demonstrating an MPR, thus advancing to stage II. Here we report interim results of the 19 pts enrolled by data cut-off 01/02/2025. Baseline stages were IIIB (53%, n = 10), IIIC (42%, n = 8) and IV (5%, n = 1); 80% cutaneous, 10% acral and 10% unknown primary melanoma. An MPR was observed in 53% (95% CI: 29,76) of pts (n = 10, 7 pCR, 3 near pCR), partial pathologic response (PR) in 21% (n = 4), and non-response in 26% (n = 5). Of the 18 evaluable, RECIST response was 28% (n = 5, all PR), 61% (n = 11) had stable disease, and 11% (n = 2) progressive disease (PD). The rate of grade >3 treatment-related adverse events (TRAE), in neoadj and adjuvant setting, was 11% (n = 2); 1 pt was hospitalized with adrenal insufficiency, no grade 5 events occurred on study. All pts proceeded to surgery with median time to surgery of 29 days (IQR 26,31). 14 pts (74%) received adjuvant therapy; 13 anti-PD-1 and 1 BRAF targeted therapy. Median follow-up was 16 months (IQR 8;23) and 12-month RFS from surgery was 91% (95% CI: 75, 100). Of the 3 pts with recurrent or progressive disease; 0 had an MPR and 2 died from progressive melanoma. CD8-PET was completed in 19 pts pre-ICB and 17 pts pre-surgery. SUVmax pre-ICB, pre-surgery and the percent change over-time was not significantly associated with MPR. CD8-PET tracer evaluation by autoradiography correlated with CD8+ cell infiltrate on IHC by pathologist assessment. Conclusions: C-IT-Neo is the first study evaluating a single dose of combination ICB in the neoadjuvant setting. Interim results show one dose has low grade 3+ TRAE and high efficacy with MPR of 53%. The trial is actively enrolling, with ongoing analysis of CD8-PET imaging and immune biomarkers. Clinical trial information: NCT05289193 .
Source: Journal of Clinical Oncology
Authors: Sarah E. Lochrin, Cecilia Lezcano, James Russell, Jeeban Paul Das, Hannah L. Kalvin, James William Smithy, Shutian Ruan, Alexander Noor Shoushtari, Parisa Momtaz, Monica F. Chen, Claire Thant, Danielle M. Bello, Edmund Bartlett, Mary Susan Brady, Charlotte Eielson Ariyan, Katherine Panageas, Neeta Pandit-Taskar, Michael A. Postow
Institution: Memorial Sloan Kettering Cancer Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Melanoma Research Alliance
OpenAlex ID: W4410818202