Long-Term Therapy With Bintrafusp Alfa in HPV-Associated Cancers

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Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor fused to a human IgG1 monoclonal antibody blocking PD-L1, showed long-term efficacy and a manageable safety profile in patients with pretreated, immune checkpoint inhibitor–naive malignancies associated with the human papillomavirus (HPV). These findings were reported by Gulley et al at the European Society for Medical Oncology (ESMO) Congress 2021 (Abstract 957O).

The research team explained that anti–PD-1/L1 agents are active in HPV-associated malignancies, with a median overall survival of ≤ 12 months. HPV infection has been linked to upregulation of tumor TGF-β signaling.

The team had previously reported a post hoc pooled analysis of patients with HPV-associated malignancies who were treated with bintrafusp alfa. At the ESMO Congress 2021, they reported longer follow-up of additional patients with HPV-associated malignancies pooled from two studies: INTR@PID 001 (phase I; identifier NCT02517398) and Study 012 (phase II; NCT03427411).

A total of 75 patients with pretreated HPV-associated malignancies received bintrafusp alfa in the phase I study until May 15, 2020, and until December 22, 2020, in the phase II study. Among all patients, 39 had cervical cancer, 19 had squamous cell carcinoma of the head and neck, 9 had anal cancer, and 8 had other cancer types. Median duration of treatment was 3.2 months (range = 0.5–29.9). Median follow-up was 33 months, and 3 patients remained on treatment.

Efficacy of Bintrafusp Alfa

The objective response rate was 28.0%, with 4 complete responses and 17 partial responses; 3 additional patients had a delayed partial response, leading to a clinical response rate of 32.0%, according to Response Evaluation Criteria in Solid Tumors. Responses occurred in various HPV-associated malignancies. Median duration of response was 17.3 months (95% confidence interval [CI] = 7.8–not evaluable).

Median overall survival was 21.3 months (95% CI = 10.8–not evaluable), with a 12-month overall survival rate of 59.7% and an 18-month rate of 51.5%.

The most common treatment-related adverse events were pruritus (25.3%; all grade 1), dermatitis acneiform (24.0%; all grade 1), and anemia (18.7%; with grade 3 anemia occurring in 6.7%). There were no deaths due to treatment-related adverse events.

The authors concluded that in this population with a high unmet medical need, bintrafusp alfa showed long-term efficacy and manageable safety. Clinical studies with bintrafusp alfa are ongoing in patients with HPV-associated malignancies.

Disclosure: This study was funded by Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline. For full disclosures of the study authors, visit

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