Cemiplimab for kidney organ transplant recipients with advanced cutaneous squamous cell carcinoma: CONTRAC-1.
Glenn J. Hanna, Harita Dharaneeswaran, Anita Giobbie‐Hurder, John Harran, Zixi Liao, Lori Pai, Vatche Tchekmedyian, Emily S. Ruiz, Abigail H. Waldman, Chrysalyne D. Schmults, Patrick H. Lizotte, Cloud P. Paweletz, Leonardo V. Riella, Naoka Murakami, Ann W. Silk
Abstract
9519 Background: Solid organ transplant recipients are often excluded from immunotherapy trials given the risk of allograft rejection and loss. We report the results of the first prospective study using the PD-1 inhibitor Cemiplimab (Cemi) for kidney transplant recipients (KTR) with advanced, incurable cutaneous squamous cell carcinoma (cSCC), adopting a standardized approach to immunosuppression (IS) with mTOR inhibition and dynamic prednisone (NCT04339062). Methods: This single-arm, open-label prospective clinical trial enrolled KTRs (eGFR ≥30 mL/min without proteinuria) with advanced cSCC, ECOG ≤2, measurable disease (RECIST v1.1), with no prior immunotherapy exposure. KTRs received mTOR inhibition (target trough 4-6 ng/mL) with a prednisone taper each cycle (40 mg on day -1 to 3, 20 mg days 4-6, 10 mg days 7-20) along with Cemi 350 mg IV every 21-days. Primary endpoint: rate of rejection (futility defined as ≥2/3 or 4/6 KTRs with rejection events). Secondary endpoints: overall response rate (ORR), duration of response, progression-free survival (PFS), overall survival (OS), infection rates. Exploratory: baseline tumor PD-L1 score, molecular and immunologic predictors of response. Results: From 11/2020 to 1/2023, 10 KTRs (median years from transplant: 8, range: 3-31) enrolled including 8 (80%) men, median age 64 (range: 43-86), median eGFR 48 (range: 32-60) often with head and neck primaries (9, 90%) and distant metastases (7, 70%). Six (60%) had prior systemic therapy. For mTOR inhibition, 7 (70%) received sirolimus and 3 (30%) everolimus. At a median follow-up of 6.3 months (range: < 1-24.9), no patients experienced kidney allograft rejection or loss. Of 8 evaluable patients, ORR was 50% (2 CR, 2 PRs), while 4 had PD. At data cutoff no responder had progressed, with 2/4 in response > 18 months (range: < 1-22.7+). One patient is pending first restaging; 1 was unevaluable (died before first restaging). One KTR with initial PD experienced a subsequent durable response to cetuximab. Fatigue (40%) and limb edema (30%) were the most common treatment-related adverse events (TRAEs). Grade 3+ TRAEs occurred in 5 (50%) patients including diarrhea, infections (n = 3), and electrolyte derangements; there were no Cemi-related deaths. Median PFS was 7.9 mos (95%CI: 1.2-not reached [NR]); the 3-month OS estimate was 61% (95%CI: 27-83). Baseline tumor PD-L1 scores ranged from 0-5%; median TMB was 49 muts/Mb (range: 10-97). Tumor mutations in TP53, CDKN2A, and NOTCH1 were common. Exploratory tumor/circulating multiparametric immune profiling and circulating tumor (ct)DNA findings will be presented. Conclusions: Using IS with mTOR inhibition and dynamic prednisone resulted in no kidney allograft rejection among KTRs treated with Cemi for advanced cSCC. Durable anti-tumor efficacy was observed. mTOR inhibition with prednisone should be the preferred IS regimen when treating KTRs with anti-PD-1 therapy. Clinical trial information: NCT04339062 .