This is a FIH study is to evaluate the safety, tolerability, PK, immunogenicity, and preliminary antitumor activity of XB010 as a single agent and in combination with pembrolizumab in subjects with locally advanced or metastatic solid tumors for whom alternative therapies do not exist or available therapies are intolerable or no longer effective.

DRUG: XB010

IV administration of XB010

DRUG: Pembrolizumab

IV administration of Pembrolizumab

• Dose-Escalation Stage: Maximum tolerated dose (MTD) and/or Recommended dose(s) for Expansion [RDE(s)] for XB010

• Dose-Escalation Stage: Safety of XB010

• Dose-Escalation Stage: Duration of exposure of XB010 [Tolerability]

• Dose-Escalation Stage: Dose intensity of XB010 [Tolerability]

• Cohort-Expansion Stage: Preliminary antitumor activity of XB010

• Irresectable/metastatic NSCLC
• non-squamous cell or squamous cell histology) with disease progression.
• WHO 0 or 1
• Participants without an actionable mutation
  o Must have received platinum-based chemotherapy and a PD-1/PD-L1 inhibitor, administered concurrently or sequentially for locally advanced or metastatic disease. Participants who are not eligible to receive ICI therapy are eligible if they have received platinum-containing doublet chemotherapy.
  o Did not receive more than 3 prior lines of systemic therapy in the metastatic setting (inclusive of ICI therapy given as monotherapy or in combination; rechallenge with the same agents is considered an additional line of therapy if prior disease progression on treatment has occurred).

• Participants with an actionable mutation (eg, EGFR sensitizing mutation, ALK rearrangement, ROS1 rearrangement, BRAF V600E mutation, MET Exon 14 skipping mutation, RET rearrangement, KRAS-G12C)
  

o have received at least one targeted therapy for that specific genetic alteration unless such therapy is not available, or the participant is not qualified to receive such therapy.
o Did not receive more than 3 prior lines of systemic therapy in the metastatic setting (inclusive of targeted therapy and ICI therapy given as monotherapy or in combination; rechallenge with the same agents is considered an additional line of therapy if prior disease progression on treatment has occurred

No earlier treatment with ADC containing a MMAE-payload: ‘… vedotine’