The Lancet Regional Health. Western Pacific (Nov 2023)

Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: a phase II clinical trialResearch in context

  • Chi Leung Chiang,
  • Tai Chung Lam,
  • James Chun Bong Li,
  • Kenneth Sik Kwan Chan,
  • Aya El Helali,
  • Yolanda Yim Ping Lee,
  • Laalaa Hiu Ting Law,
  • Danyang Zheng,
  • Anthony Wing Ip Lo,
  • Ngar Woon Kam,
  • Wing Sum Li,
  • Alice Ka Wai Cheung,
  • James Chung Hang Chow,
  • Sunny Po Chung Chan,
  • Jessica Wing Yu Lai,
  • Sarah Wai Man Lee,
  • Feng-Ming (Spring) Kong,
  • Wai Tong Ng,
  • Dora Lai Wan Kwong,
  • Anne Wing Mui Lee

Journal volume & issue
Vol. 40
p. 100898

Abstract

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Summary: Background: The strategy of dual blockade of TGF-β and PD-L1 pathways has not been previously tested in platinum-refractory recurrent or metastatic nasopharyngeal cancer (R/M NPC) patients. This study aimed to evaluate the safety and efficacy of bintrafusp alfa in refractory R/M NPC patients. Methods: In this single-arm, single-centre phase II clinical trial, 38 histologically confirmed R/M NPC patients were enrolled and administered with bintrafusp alfa every 2 weeks. Primary endpoint was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Findings: Thirty-eight patients were accrued (33 men; median age, 54 years). ORR was 23.7% (complete response, n = 2; partial response, n = 7). The median DOR was 19.2 months, median PFS was 2.3 months, median OS was 17.0 months, and 1-year OS rate was 63.2%. Unfortunately, 25 patients (65.7%) progressed within 8 weeks of treatment, 15 patients (39.5%) and 8 patients (21.1%) developed hyper-progressive disease (HPD) per RECIST v1.1 and tumor growth rate (TGR) ratio respectively. Sixteen patients (42.4%) experienced ≥ grade 3 treatment-related adverse events (TRAEs), most commonly anemia (n = 9, 23.7%) and secondary malignancies (n = 4, 10.5%). TRAEs led to permanent treatment discontinuation in 7 patients. Patients with strong suppression of plasma TGFβ1 level at week 8 were unexpectedly associated with worse ORR (9.1% vs 44.4%, P = 0.046) and development of HPD. There was no correlation between PD-L1 expression and ORR. Interpretation: Bintrafusp alfa demonstrated modest activity in R/M NPC but high rates of HPD and treatment discontinuation secondary to TRAEs are concerning. Funding: The project was supported by Alice Ho Miu Ling Nethersole Charity Foundation Professorship Endowed Fund and Merck KGaA.

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