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

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

doi:10.1016/j.lanwpc.2023.100898

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

Lancet Reg Health West Pac. 2023 Sep 6:40:100898. doi: 10.1016/j.lanwpc.2023.100898. eCollection 2023 Nov.

Authors

Chi Leung Chiang¹, Tai Chung Lam¹, James Chun Bong Li², Kenneth Sik Kwan Chan³, Aya El Helali³, Yolanda Yim Ping Lee⁴, Laalaa Hiu Ting Law², Danyang Zheng³, Anthony Wing Ip Lo⁵, Ngar Woon Kam³, Wing Sum Li⁶, Alice Ka Wai Cheung⁷, James Chung Hang Chow⁶, Sunny Po Chung Chan⁷, Jessica Wing Yu Lai⁸, Sarah Wai Man Lee⁹, Feng-Ming Spring Kong¹, Wai Tong Ng¹, Dora Lai Wan Kwong¹, Anne Wing Mui Lee¹⁰

Affiliations

¹ LKS Faculty of Medicine, Department of Clinical Oncology, School of Clinical Medicine, The University of Hong Kong and University of Hong Kong-Shenzhen Hospital, China.
² LKS Faculty of Medicine, Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, The University of Hong Kong, China.
³ LKS Faculty of Medicine, Department of Clinical Oncology, School of Clinical Medicine, The University of Hong Kong, China.
⁴ Department of Diagnostic Radiology, Gleneagles Hospital (Hong Kong), China.
⁵ Department of Pathology, Queen Mary Hospital, Hong Kong, China.
⁶ Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China.
⁷ Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China.
⁸ Department of Clinical Oncology, Princess Margaret Hospital, Hong Kong, China.
⁹ Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, China.
¹⁰ LKS Faculty of Medicine, Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital and School of Clinical Medicine, The University of Hong Kong, China.

Abstract

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.

Keywords: Bintrafusp alfa; Correlative biomarkers; Efficacy; Recurrent or metastatic nasopharyngeal cancer; Safety.