A Pilot Study of the CD38 Antagonist Daratumumab in Patients with Metastatic Renal Cell Carcinoma or Muscle-Invasive Bladder Cancer

Authors

Matthew T Campbell
Amishi Y Shah
Pavlos Msaouel
Nizar M Tannir
Arlene O Siefker-Radtke
Ashish M Kamat
Neema Navai
Colin P N Dinney
Priya Rao
Charles C Guo
Rahul A Sheth
Aradhana M Venkatesan
Rebecca S Tidwell
Shalini S Yadav
Aidi Gu
Hong Chen
Marc Macaluso
Fei Duan
Sreyashi Basu
Sonali Jindal
Padmanee Sharma

Publication Date

9-1-2024

Journal

Cancer Research Communications

Abstract

PURPOSE: We performed a pilot study of daratumumab (an mAb directed against CD38) in muscle-invasive bladder cancer (MIBC) and treatment-refractory metastatic renal cell carcinoma (mRCC).

EXPERIMENTAL DESIGN: Patients with MIBC underwent baseline transurethral resection of the bladder tumor followed by four weekly doses of daratumumab prior to cystectomy. Patients with mRCC underwent baseline and sequential biopsies after eight weekly doses. The primary endpoint was safety. The secondary endpoints were pathologic complete response rate for the MIBC cohort and objective response rate and progression-free survival for the mRCC cohort. Exploratory analyses included immune monitoring and overall survival. A Bayesian sequential monitoring design for toxicity was used for excessive toxicity.

RESULTS: In both the MIBC (n = 8) and mRCC (n = 8) cohorts, no toxicity events were encountered. In the MIBC cohort, one patient experienced pathologic complete response rate. In the mRCC cohort, no objective responses were reported, and the median progression-free survival was 1.5 months (95% confidence interval, 1.1-1.8 months). Immune monitoring found significant reductions in NK cells in circulation in both cohorts after treatment. In the tissue analysis, IHC found evidence of diminished CD38 presence in mRCC with treatment, whereas the baseline levels in MIBC were low.

CONCLUSION: Treatment with daratumumab was safe. No signal of efficacy was detected in mRCC, and conclusions on the activity in MIBC were limited. Evidence of daratumumab targeting CD38 was detected in circulating immune cells and within the tumor microenvironment of mRCC and MIBC.

SIGNIFICANCE: In this prospective clinical trial of daratumumab, treatment in patients with MIBC and mRCC was safe. Limited efficacy was observed. Treatment with daratumumab resulted in CD38-expressing immune cell subsets to be targeted both in circulation and within the tumor microenvironment.

Keywords

Humans, Pilot Projects, Antibodies, Monoclonal, Male, ADP-ribosyl Cyclase 1, Aged, Female, Middle Aged, Urinary Bladder Neoplasms, Carcinoma, Renal Cell, Kidney Neoplasms, Neoplasm Invasiveness, Progression-Free Survival, Aged, 80 and over, Membrane Glycoproteins

Comments

Supplementary Materials

Data Availability Statement

PMID: 39207194