Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients With HER2-Expressing Solid Tumors: A Phase 1 Dose Escalation Study

Document Type

Journal Article

Publication Date



Molecular cancer therapeutics




PF-06804103 is an anti-HER2 antibody-drug conjugate with auristatin payload. We evaluated its safety, tolerability, and antitumor activity in patients with advanced/unresectable or metastatic breast cancer and gastric cancer. This multicenter, open-label, first-in-human, phase 1 study (NCT03284723) comprised dose escalation (P1) and dose expansion (P2). In P1, adults with HER2+ breast or gastric cancer received PF-06804103 0.15-5.0 mg/kg intravenously once/21 days (Q3W); in P2, patients with HER2+ or HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-) breast cancer received 3.0 or 4.0 mg/kg Q3W. The primary endpoints were dose-limiting toxicities (DLTs) and safety (P1), and objective response rate (ORR) assessed using RECIST v1.1 (P2). Ninety-three patients enrolled in P1 (n=47: HER2+ gastric cancer=22, HER2+ breast cancer=25) and P2 (n=46: HER2+ breast cancer=19, hormone receptor [HR]+ HER2-low breast cancer=27) received PF-06804103. Four patients (3.0- and 4.0-mg/kg groups, n=2 each) had DLTs (mostly Grade 3). Safety and efficacy results showed a dose-response relationship. Adverse events leading to treatment discontinuation (44/93, 47.3%) included neuropathy (11/93, 11.8%), skin toxicity (9/93, 9.7%), myalgia (5/93, 5.4%), keratitis (3/93, 3.2%), and arthralgia (2/93, 2.2%). Two (2/79, 2.5%) patients (P1, 4.0- and 5.0-mg/kg groups, n=1 each) achieved complete response; 21 (21/79, 26.6%) achieved partial response. In P2, ORR was higher in HER2+ compared with HR+ HER2-low breast cancer (3.0 mg/kg: 16.7% [2/12] vs 10.0% [1/10]; 4.0 mg/kg: 47.4% [9/19] vs 27.3% [3/11]). PF-06804103 demonstrated antitumor activity; however, adverse events led to discontinuation in 47.3% of patients. Safety and efficacy were dose-dependent. Clinical trial registration: NCT03284723.