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Updated: Jul 9, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Phase I Study of Androgen Deprivation Therapy in Combination with Anti-PD-1 in Melanoma Patients Pretreated with
Caroline Robert1, Céleste Lebbé2, Thierry Lesimple3
1Gustave Roussy and Paris Saclay University, Villejuif, France.
Purpose:
Androgen deprivation regenerates the thymus in adults, expanding of T-cell receptor V β repertoire in blood and lymphoid organs and tumor-infiltrating lymphocytes in human prostate tumors. In melanoma murine models, androgen receptor promotes metastases and androgen blockade potentiates antitumor vaccine efficacy. This phase I study evaluated the safety, efficacy, and pharmocodynamics of androgen deprivation with the gonadotropin releasing hormone (GnRH) agonist triptorelin combined with nivolumab in male patients with melanoma resistant to anti-PD-1.
Patients And Methods:
Adult male patients with advanced melanoma who progressed under anti-PD-1 containing regimens received triptorelin 3.75 mg every 4 weeks, nivolumab 3 mg/kg every 2 weeks, and bicalutamide 50 mg once daily during the first 28 days. Tumor response was first assessed after 3 months; adverse events (AE) were monitored throughout the study. T-cell receptor excision circles (TREC), a biomarker of thymus activity, were explored throughout the study.
Results:
Of 14 patients, 4 were locally advanced and 10 had distant metastases. There were no grade 4 or 5 AEs. Five grade three AEs were reported in 4 patients. According to RECIST v1.1, best overall response was partial response (PR) in one patient with a pancreas metastasis, stable disease (SD) in 5 patients, and progressive disease in 8 patients. According to iRECIST, a second PR occurred after an initial pseudoprogression, TRECs increased in 2 patients, one with PR who also had an increase in TILs, and the second with SD.
Conclusions:
This combination was well tolerated. Disease control was obtained in 42.8% (RECIST) and 50% (iRECIST). The evidence for thymus rejuvenation was limited.
Insights
Androgen deprivation combined with nivolumab showed limited evidence of thymus regeneration but achieved disease control in 42.8% of advanced melanoma patients resistant to anti-PD-1 therapy.
Area of Science:
- Immunology
- Oncology
- Endocrinology
Background:
- Androgen deprivation can regenerate the thymus and expand T-cell receptor V β repertoire.
- Androgen receptor blockade may enhance antitumor vaccine efficacy in melanoma models.
- This study investigates a novel combination therapy for advanced melanoma.
Purpose of the Study:
- Evaluate the safety and efficacy of androgen deprivation using a GnRH agonist (triptorelin) combined with nivolumab.
- Assess the pharmacodynamics of this combination in male patients with anti-PD-1 resistant melanoma.
- Explore the impact on thymus activity and T-cell receptor excision circles (TRECs).
Main Methods:
- Phase I clinical trial involving adult male patients with advanced melanoma.
- Treatment regimen: triptorelin, nivolumab, and bicalutamide.
- Tumor response assessed by RECIST v1.1 and iRECIST; adverse events and TRECs monitored.
Main Results:
- 14 patients enrolled; 4 locally advanced, 10 with distant metastases.
- No grade 4 or 5 adverse events; 5 grade 3 adverse events in 4 patients.
- Partial response in 1 patient, stable disease in 5 patients (RECIST); disease control rate of 42.8% (RECIST) and 50% (iRECIST).
Conclusions:
- The combination of triptorelin and nivolumab was well-tolerated in advanced melanoma patients.
- Achieved disease control in a significant portion of patients resistant to anti-PD-1 therapy.
- Evidence for thymus rejuvenation was limited in this study population.
