957O - Long-term follow-up of patients (pts) with human papillomavirus (HPV)–associated malignancies treated with bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1

Background

Anti–PD(L)1 agents have activity in HPV-associated cancers (HAC), with median overall survival (mOS) of ≤12 months (mos). HPV infection has been linked to upregulation of tumor TGF-β signaling. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β “trap”) fused to a human IgG1 mAb blocking PD-L1. Previously we reported a post hoc pooled analysis of pts with HAC treated with bintrafusp alfa. Here we report longer follow-up of additional pts with HAC pooled from phase (Ph) 1 (INTR@PID 001; NCT02517398) and Ph 2 (study 012; NCT03427411) studies.

Methods

Pts with advanced, pretreated, immune checkpoint inhibitor (ICI)–naive HAC who had exhausted standard-of-care treatment received bintrafusp alfa 0.3-30 mg/kg (Ph 1 dose escalation) or 1200 mg Q2W (Ph 1 expansion/Ph 2) until progressive disease, unacceptable toxicity, or withdrawal. Treatment past progression was allowed. Primary endpoints were safety (Ph 1 dose escalation) and best overall response per RECIST v1.1 (Ph 1 expansion/Ph 2).

Results

As of 15 May 2020 (Ph 1) and 22 December 2020 (Ph 2), 75 pts with pretreated HAC (cervical 39, SCCHN 19, anal 9, other 8) had received bintrafusp alfa for a median duration of 3.2 mos (range, 0.5-29.9 mos) and been followed for a median of 33 mos; 3 pts remained on treatment. ORR was 28.0% [4 CRs; 17 PRs]; 3 more pts had a delayed PR, for a clinical response rate (RECIST response + delayed response) of 32.0%. Responses occurred in various HAC. Median duration of response (mDOR) was 17.3 (95% CI, 7.8-NE) mos. Median OS was 21.3 (95% CI, 10.8-NE) mos; 12- and 18-mo OS rates were 59.7% and 51.5%, respectively. The most common treatment-related adverse events (TRAEs) were pruritus (25.3%, all events grade 1), dermatitis acneiform (24.0%, all grade 1), and anaemia (18.7%, grade 3 [6.7%]); no deaths due to TRAEs were observed.

Conclusions

Bintrafusp alfa showed long-term efficacy (mDOR 17.3 mos, mOS 21.3 mos) and a manageable safety profile in pts with pretreated, ICI-naive HAC, a pt population with a high unmet need. Clinical trials of bintrafusp alfa in HAC are ongoing.

Clinical trial identification

INTR@PID 001: NCT02517398; Study 012: NCT03427411.

Editorial acknowledgement

Medical writing support was provided by Marci Daugherty, PharmD of ClinicalThinking, Inc, Hamilton, NJ, USA, and funded by Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.

Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany.

Funding

Merck KGaA, Darmstadt, Germany, and GlaxoSmithKline.

Disclosure

J. Strauss: Financial Interests, Personal, Other, listed as a coinventor on an NIH patent: National Institutes of Health. B.C. Cho: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MOGAM Institute; Financial Interests, Institutional, Research Grant: Dong-A ST; Financial Interests, Institutional, Research Grant: Champions Onocology; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: Yuhan; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Dizal Pharma; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Abbvie; Financial Interests, Institutional, Research Grant: Medpacto; Financial Interests, Institutional, Research Grant: GIInnovation; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Institutional, Research Grant: Interpark Bio Convergence Corp; Financial Interests, Personal, Advisory Role: KANAPH Therapeutic Inc.; Financial Interests, Personal, Advisory Role: Bridgebio Therapeutics; Financial Interests, Personal, Advisory Role: Cryrus Therapeutics; Financial Interests, Personal, Advisory Role: Gaurdant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc.; Financial Interests, Personal, Stocks/Shares: Gencurix Inc.; Financial Interests, Personal, Stocks/Shares: Bridgebio Therapeutics; Financial Interests, Personal, Stocks/Shares: KANAPH Therapeutic Inc.; Financial Interests, Personal, Stocks/Shares: Cyrus Therapeutics; Financial Interests, Personal, Stocks/Shares: Interpark Bio; Financial Interests, Personal, Stocks/Shares: Convergence Corp; Financial Interests, Personal, Other, Consulting Role: Novartis; Financial Interests, Personal, Other, Consulting Role: AstraZeneca; Financial Interests, Personal, Other, Consulting Role: Boehringer-Ingelheim; Financial Interests, Personal, Other, Consulting Role: Roche BMS; Financial Interests, Personal, Other, Consulting Role: Ono; Financial Interests, Personal, Other, Consulting Role: Yuhan; Financial Interests, Personal, Other, Consulting Role: Pfizer; Financial Interests, Personal, Other, Consulting Role: Eli Lilly; Financial Interests, Personal, Other, Consulting Role: Janssen; Financial Interests, Personal, Other, Consulting Role: Takeda; Financial Interests, Personal, Other, Consulting Role: MSD; Financial Interests, Personal, Other, Consulting Role: Medpacto; Financial Interests, Personal, Other, Consulting Role: Blueprint Medicines; Financial Interests, Personal, Other, Board of Director: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. S. Salas: Financial Interests, Personal, Full or part-time Employment: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Merck & Co.; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb. E. McClay: Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Merck; Financial Interests, Personal, Speaker’s Bureau: Pfizer. E. Lamping: Financial Interests, Personal, Full or part-time Employment: NCI/NIH. G. Jehl: Financial Interests, Personal, Full or part-time Employment: Merck KGaA. L.S. Ojalvo: Financial Interests, Personal, Full or part-time Employment: EMD Serono Research & Development Institute, Inc.; Financial Interests, Personal, Other, IP/Patent holder: EMD Serono Research & Development Institute, Inc. J. Gulley: Financial Interests, Institutional, Other, NCI has a cooperative research and development agreement: EMD Serono / Merck KGaA. All other authors have declared no conflicts of interest.