A randomized, multicenter, phase II trial of camrelizumab (Cam) with and without metastasis-directed therapy (MDT) in recurrent/metastatic nasopharyngeal carcinoma (R/M-NPC).

141 Background: To investigate the on- and off-target treatment responses of MDT when added to camrelizumab – an anti-programmed cell death 1 antibody in patients with R/M-NPC. Methods: We conducted an open-label, randomized, controlled, multicenter, phase II trial in 3 centers from China (NCT04830267). Patients with R/M NPC, without prior exposure to immune checkpoint inhibitors, who presented with ≥2 lesions, and at least 1 measurable lesion were screened and randomized 1:1 to either Cam (200 mg IV 2-weekly) alone or Cam plus MDT (Cam+MDT). Patients randomized to the MDT group must have 1 lesion that is amendable to MDT using stereotactic body radiotherapy (SBRT) prescribed to 27Gy in 3 fractions every other day between the first and second dose of Cam. Primary endpoint was off-target objective response rate (ORR) by RECIST v1.1. Secondary endpoints included on-target ORR, disease control rate (DCR), progression-free (PFS), overall survival (OS), and safety. Results: Between March 1, 2021, and August 16, 2023, 39 patients with R/M NPC were randomly assigned to receive either Cam alone (n=20) or Cam+MDT (n=19). 17/39 (44%) patients had oligometastatic disease (≤3 lesions); 18/39 (46%) had liver metastasis. Median duration of Cam was 4.1 mo (95%CI: 2.4-10.9) and 4.7 mo (95% CI: 2.3-11.0) in both treatment groups, respectively. Sites of MDT included lungs (8/19, 42%), followed by liver (4/19, 21%), bones (4/19, 21%), and lymph nodes (3/19, 16%); median SBRT target volume was 5.8 cc (IQR: 2.7-13.5). Off-target ORR did not differ between the treatment groups (26% vs 30%, P=0.51), although DCR was 74% in the Cam+MDT group compared with 60% in the Cam only group ( P=0.37, Table). After a median follow up of 25.8 mo, median PFS was 9.3 mo (95% CI:6.2-NR) in the Cam+MDT group and 8.8 mo (95% CI: 3.3-NR) in the Cam group (P=0.75), and median OS was not reached in the Cam+MDT gorup (95% CI: 20-NR) and 13.7 mo (95% CI: 11-NR) in the Cam group. Interestingly, exploratory analyses suggest a longer OS with Cam+MDT for patients with >3 metastatic lesions ( HR 0.228 [95% CI: 0.067-0.769]), and no liver involvement ( HR 0.287 [95% CI: 0.068-1.208]). G3 and above adverse events were comparable between the treatment groups (14.3% vs 12.5%). Conclusions: We did not observe a difference for off-target ORR with the addition of MDT to Cam in patients with R/M-NPC, although DCR was higher with combinatorial treatment due to a higher proportion of stable disease. Interestingly, OS was prolonged with Cam+MDT in a subset of patients with >3 lesions and no liver involvement. Clinical trial information: NCT04830267 . [Table: see text]