Inclusion criteria require confirmed advanced solid tumors across multiple indications (NSCLC, breast cancers, HNSCC, etc.), age &ge;18, ECOG 0-1, measurable disease by RECIST v1.1, adequate organ function (hematologic/hepatic/renal), and QTcF <470 msec. Exclusions include active CNS metastases, uncontrolled CV disease, unresolved toxicity (>Grade 1), prior EDB+FN therapy, high-risk infections (HBV/HCV/HIV), recent anticancer therapy (28 days), and visual/corneal impairments. Safety monitoring continues in Part 2 (AEs up to 2 years).

This segment covers safety assessments for Part 1, including Dose-Limiting Toxicities (DLTs) defined by protocol-specific criteria occurring within the first 21 days of treatment, and adverse events (AEs) monitored for approximately 3 years with grading based on NCI-CTCAE v5.0. It also introduces Objective Response Rate (ORR) in Part 2 as a key efficacy endpoint evaluated up to 2 years.

This section details pharmacokinetic parameters (Cmax, Tmax, CL, AUC0-t, AUCtau, AUC0-inf, t½) for PYX-201 components in Part 1, measured over 2 years, alongside clinical response metrics (ORR, DOR, PFS, DCR, TTR, OS) with follow-up to 3 years. Part 2 data includes efficacy endpoints (DOR, CBR, mPFS, DCR, TTR, mOS) and drug concentration measures (Cmax, Tmax, trough levels), extending observation to approximately 4 years for survival outcomes.

Inclusion criteria require advanced solid tumors (HNSCC, TNBC, HR+/HER2- BC, GC, cervical cancer), age &ge;18, ECOG PS 0-1, measurable disease per RECIST v1.1, life expectancy >3 months, and adequate organ function. Exclusion criteria include active CNS metastases, uncontrolled infections (HBV/HCV/HIV), unresolved prior toxicities (>Grade 1), autoimmune disease, prior PD-1/L1 inhibitors, and severe hypersensitivity to study drugs or excipients. Strict eligibility ensures patient safety and measurable efficacy assessment.

Experimental: Part 1: Dose Escalation, Participants will receive escalating doses of PYX-201 to evaluate the safety, tolerability, and preliminary efficacy of PYX-201 in combination with pembrolizumab.Experimental: Part 2: Dose Expansion, Part 2 dose-expansion cohorts will be opened based on emerging data to further inform the safety, tolerability, and preliminary efficacy determinations as defined.

This segment outlines efficacy and pharmacokinetic assessments, evaluating Objective Response Rate (ORR), Duration of Response (DOR), Disease Control Rate (DCR), Time to Response, and Clinical Benefit Rate (CBR) over ~2 years. Pharmacokinetic analysis includes Cmax, Tmax, Clearance (CL), AUC (0-t, tau, and 0-inf), half-life (t½) for ADC, total antibody, and free payload, along with immunogenicity assessment via anti-drug antibodies.