Inclusion criteria cover HER2+/- breast/gastric cancer (Part 1A/B, Part 2A/B) resistant to standard therapy, with PS 0-1 and adequate organ function. Exclusions include CNS metastases, anthracycline overdose, Grade 3+ antibody hypersensitivity, active infections, LVEF <50%, or interstitial lung disease. Eligibility is tailored by study part, emphasizing safety and biomarker relevance.

This multi-center, open-label, first-in-patient, phase I study (NCT03284723) has two parts: dose escalation (Part 1) and dose expansion (Part 2). In Part 1, groups of adult patients (pts) with HER2+ BC or HER2+ GC, who are resistant or intolerant to standard therapy or for which no standard therapy is available, received PF-06804103 intravenously once every 21 days (Q3W); dosage was escalated per cohort. Primary objectives were to evaluate the safety and tolerability of PF-06804103, characterize its dose-limiting toxicities (DLTs), and determine the recommended phase 2 dose.

This section outlines Dose-Limiting Toxicities (DLTs) observed in Part 1A (21-day cycle) and Part 1B (28-day cycle) during the first treatment cycle, categorizing them into hematologic (Grade 4 neutropenia >7 days, febrile neutropenia, thrombocytopenia with bleeding) and non-hematologic (Grade ≥3 toxicities, treatment delays, liver abnormalities). It also details Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), including definitions and timeframes (up to 89.3 weeks for Part 1A, 53.7 weeks for Part 1B). Laboratory abnormalities (hematology, chemistry, urinalysis) and vital sign criteria are summarized, along with response metrics (Objective Response, Duration of Response, PFS, TTP) in Part 2, all assessed per RECIST v1.1.

This segment focuses on clinical outcomes in Part 1 (Objective Response, DR, PFS, TTP) with assessment intervals every 6 (Part 1A) or 8 weeks (Part 1B). Immunogenicity (anti-drug antibodies) and HER2 tumor analysis are included. Pharmacokinetic parameters (Cmax, t1/2, AUCinf, AUCtau, CL, Vss, Rac) for PF-06804103 ADC, total antibody, and unconjugated payload (PF-06380101) are detailed, with data from Part 1A/B (sparse sampling excluded Part 2A). Key metrics like terminal half-life, clearance, and volume of distribution are calculated per dosing intervals (504h for Part 1A, 336h for Part 1B).

In cell line xenograft (CLX) studies, nude mice were injected subcutaneously in the flank with suspensions of 10 x10⁶ BT474 cells, in 50% Matrigel (BD Biosciences). Mice were randomized into study groups when tumors reached approximately 150-300 mm³. Either PBS (Gibco, catalog no., 14190-144, as vehicle), PF-06804103, or PT-DM1 at different doses was administered intravenously starting on day 0 for a total of four doses, 4 days apart (four times every 4 days).

In cell line xenograft (CLX) studies, nude mice were injected subcutaneously in the flank with suspensions of 1 x10⁶ NCI-N87, in 50% Matrigel (BD Biosciences). Mice were randomized into study groups when tumors reached approximately 150-300 mm³. Either PBS (Gibco, catalog no., 14190-144, as vehicle), PF-06804103, or PT-DM1 at different doses was administered intravenously starting on day 0 for a total of four doses, 4 days apart (four times every 4 days).