Details

Autor(en) / Beteiligte

• Bajor, David L.
• Mick, Rosemarie
• Riese, Matthew J.
• Huang, Alex C.
• Sullivan, Brendan
• Richman, Lee P.
• Torigian, Drew A.
• George, Sangeeth M.
• Stelekati, Erietta
• Chen, Fang
• Melenhorst, J. Joseph
• Lacey, Simon F.
• Xu, Xiaowei
• Wherry, E. John
• Gangadhar, Tara C.
• Amaravadi, Ravi K.
• Schuchter, Lynn M.
• Vonderheide, Robert H.

Titel

Long-term outcomes of a phase I study of agonist CD40 antibody and CTLA-4 blockade in patients with metastatic melanoma

Ist Teil von

• Oncoimmunology, 2018-10, Vol.7 (10), p.e1468956-e1468956

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• We report long-term clinical outcomes and immune responses observed from a phase 1 trial of agonist CD40 monoclonal antibody (mAb) and blocking CTLA-4 mAb in patients with metastatic melanoma. Twenty-four patients previously untreated with checkpoint blockade were enrolled. The agonistic CD40 mAb CP-870,893 and the CTLA-4 blocking mAb tremelimumab were dosed concomitantly every 3 weeks and 12 weeks, respectively, across four dose combinations. Two patients developed dose-limiting grade 3 immune-mediated colitis that led to the definition of the maximum tolerated dose (MTD). Other immune-mediated toxicity included uveitis (n = 1), hypophysitis (n = 1), hypothyroidism (n = 2), and grade 3 cytokine release syndrome (CRS) (n = 1). The estimated MTD was 0.2 mg/kg of CP-870,893 and 10 mg/kg of tremelimumab. In 22 evaluable patients, the objective response rate (ORR) was 27.3%: two patients (9.1%) had complete responses (CR) and four (18.2%) patients had partial responses (PR). With a median follow-up of 45 months, the median progression-free survival (PFS) was 3.2 months (95% CI, 1.3-5.1 months) and median overall survival (OS) was 23.6 months (95% CI, 11.7-35.5 months). Nine patients are long-term survivors (> 3 years), 8 of whom subsequently received other therapy including PD-1 mAb, surgery, or radiation therapy. Elevated baseline soluble CD25 was associated with shorter OS. Immunologically, treatment was associated with evidence of T cell activation and increased tumor T cell infiltration that was accomplished without therapeutic PD-1/PD-L1 blockade. These results suggest opportunities for immune activation and cancer immunotherapy beyond PD-1.