KEY TAKEAWAYS
- The phase 2 PRINCE (NCT03214250) study aimed to investigate the efficacy of sotigalimab and nivolumab with chemotherapy in patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC).
- The method involved analyzing 105 patients for efficacy, including secondary endpoints such as progression-free survival, objective response rate, disease control rate, duration of response, and safety.
- The outcome revealed that the primary endpoint of 1-year OS was met for nivolumab/chemo but not for sotigalimab/chemo or sotigalimab/nivolumab/chemo.
Arandomized phase 2 trial (NCT03214250) to evaluate the efficacy of gemcitabine/nab-paclitaxel (chemotherapy) combined with nivolumab (nivo; anti-PD-1) and sotigalimab (sotiga; CD40 agonistic antibody) in patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC) was conducted. Nivo/chemo achieved the primary goal of 1-year overall survival (OS) of the 105 patients assessed for effectiveness (57.7%, P = 0.006 compared to historical 1-year OS of 35%, n = 34). Sotiga/chemo (48.1%, P = 0.062, n = 36) or sotiga/nivo/chemo (41.3%, P = 0.223, n = 35) did not achieve the primary goal.
The study also examined secondary endpoints, including progression-free survival, objective response rate, disease control rate, duration of response, and safety, with treatment-related adverse event rates similar across all arms. Multi-omic analyses of circulating and tumor biomarkers revealed immune signatures linked to survival for nivo/chemo and sotiga/chemo, with survival after nivo/chemo being connected to a less suppressive tumor microenvironment, significantly more circulating T cells that had been exposed to antigens at baseline. In contrast, survival after sotiga/chemo was associated with greater intratumoral CD4 T cell infiltration, circulating differentiated CD4 T cells, and antigen-presenting cells. However, no specific patient subset that would benefit from sotiga/nivo/chemo was identified. These findings revealed that the study might help identify treatment-specific correlates of efficacy and aid in selecting biomarker-selected patient populations for future PDAC chemoimmunotherapy trials.
Source: https://pubmed.ncbi.nlm.nih.gov/35662283/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03214250/
Padrón LJ, Maurer DM, O’Hara MH, O’Reilly EM, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Yu JX, Pfeiffer SM, Spasic M, Xu J, Gherardini PF, Karakunnel J, Mick R, Alanio C, Byrne KT, Hollmann TJ, Moore JS, Jones DD, Tognetti M, Chen RO, Yang X, Salvador L, Wherry EJ, Dugan U, O’Donnell-Tormey J, Butterfield LH, Hubbard-Lucey VM, Ibrahim R, Fairchild J, Bucktrout S, LaVallee TM, Vonderheide RH. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022 Jun;28(6):1167-1177. doi 10.1038/s41591-022-01829-9. Epub 2022 Jun 3. PMID: 35662283; PMCID: PMC9205784.
