Abstract 5715
Background
MCC is an aggressive cutaneous malignancy. Though checkpoint inhibitor therapy has dramatically improved the treatment landscape, outcome remains poor for those that are refractory to anti-PD1/PDL1 therapy. Combination checkpoint inhibition and the use of radiation therapy have been proposed as potentially synergistic interventions to improve immunotherapy (IT) response rates (RR).
Methods
In this multi-institutional trial, we enrolled patients (pts) with metastatic or recurrent MCC, ECOG PS 0-1, with at least 2 distinct metastatic lesions. Prior chemotherapy or immunotherapy was permitted. Primary endpoint was objective RR. In a randomized design of 2 experimental arms, pts received NIVO 240mg IV q2 wks plus IPI 1mg/kg IV q6 wks (arm A), or the same combination plus SBRT to 24Gy in 3 fractions between cycles 1 and 2 (arm B). Each arm uses a Simon Mini-Max two-stage design for futility, with total accrual of 50 assuming full accrual.
Results
To date, 16 pts have been enrolled, including 4 treatment-naïve and 12 PD1/PDL1-refractory pts. 11 pts were male and 5 pts female. Median age at enrollment was 75.5. On Arm A, the RR was 80% (1 CR, 3 PR) in 4/5 evaluable pts. On Arm B, the RR was 17% (1 PR) among 6 evaluable pts. 4 pts are pending initial staging and 1 pt expired prior to first evaluation. Collectively, 2/8 (25%) PD1/PDL1refractory pts and 3/3 (100%) IT-naïve pts have achieved CR/PR. 7 pts experienced > G2 immune toxicity (1 G3 myocarditis, 1 G3 colitis, 1 G2 arthritis, 1 G2 cough, 3 G2 dermatitis, 1 G2 neurotoxicity, 1 G2 blurred vision, 1 G2 abdominal pain, 2 G2 hypothyroidism, 1 G2 renal insufficiency). 1 pt was taken off the trial due to toxicity.
Conclusions
NIVO + IPI is safe and demonstrates promising initial efficacy in advanced MCC in both PD1/PDL1-naïve and refractory cases. SBRT can be safely added to this and its contribution to efficacy is being explored pending futility analysis. Arm A of the trial has already met efficacy criteria to proceed to full accrual.
Clinical trial identification
NCT03071406.
Editorial acknowledgement
Legal entity responsible for the study
H. Lee. Moffitt Cancer Center & Research Institute.
Funding
Bristol-Myers Squibb.
Disclosure
S. Kim: Research grant / Funding (institution), IIT funded through BMS rare malignancy program: BMS. N.I. Khushalani: Advisory / Consultancy: BMS. L. Harrison: Research grant / Funding (self): Viewray. All other authors have declared no conflicts of interest.
Resources from the same session
5763 - cfDNA is an acceptable but insufficient means of characterizing FGFR3 mutation in patients with metastatic urothelial cancer (mUC)
Presenter: Sumanta Pal
Session: Poster Display session 3
Resources:
Abstract
5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Presenter: Jonas Jarczyk
Session: Poster Display session 3
Resources:
Abstract
5204 - A differential bladder microbiota composition is associated with tumor grade in bladder cancer.
Presenter: Monica Parra-Grande
Session: Poster Display session 3
Resources:
Abstract
4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)
Presenter: Victor Sacristan Santos
Session: Poster Display session 3
Resources:
Abstract
5370 - Evaluation of different diagnostic methods for identification of FGFR alteration in advanced urothelial carcinomas: Proficiency Results based on multiple RNA extraction kits and mutation detection methods
Presenter: Veronika Weyerer
Session: Poster Display session 3
Resources:
Abstract
2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers
Presenter: Esmail Al-ezzi
Session: Poster Display session 3
Resources:
Abstract
2203 - TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy
Session: Poster Display session 3
Resources:
Abstract
4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B
Presenter: Cristina Suárez
Session: Poster Display session 3
Resources:
Abstract
2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A
Presenter: James Larkin
Session: Poster Display session 3
Resources:
Abstract
2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract