BACKGROUND: PF-07209960 is an antibody-cytokine fusion molecule that consists of a single potency-reduced interleukin-15 (IL-15) mutein and a bivalent high-affinity anti-programmed cell death protein 1 (PD-1) full-length IgG. This phase I study (NCT04628780) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and potential clinical benefits of PF-07209960 in patients with selected locally advanced or metastatic solid tumors for whom no standard therapy was available. MATERIALS AND METHODS: Escalating doses (1-30 mg) of PF-07209960 were administered subcutaneously once every 2 weeks in 28-day cycles. The primary endpoints included dose-limiting toxicities (DLTs), adverse events (AEs), and laboratory abnormalities. The secondary endpoints included PK, anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against PF-07209960, and tumor response assessed using RECIST version 1.1. RESULTS: Thirty-seven patients received treatment with PF-07209960 (1-, 3-, and 10-mg groups, n = 4 each
15 mg, n = 3
20 mg, n = 16
30 mg, n = 6). The median age was 59.0 years (range 31-88 years). Six (22.2%) patients had DLTs. The most frequently reported treatment-related AEs (TRAEs) (≥50%) were general disorders and administration site condition [21 (56.8%)] and skin and subcutaneous tissue disorders [20 (54.1%)]. The most frequently reported grade ≥3 TRAE was anemia [5 (13.5%)]. Two patients with microsatellite-stable colorectal cancer had confirmed partial response, one each from the PF-07209960 20-mg and 30-mg cohorts, with a duration of response of 9.5 and 3 months, respectively. The rate of ADA was 93.9% (31/33), of which 63.6% (21/33) was treatment induced and 30.3% (10/33) was treatment boosted. CONCLUSION: PF-07209960 was generally manageable, with potential antitumor activity in some patients.