A Phase 1, Open-label, Multicenter, Safety, Pharmacokinetic, Pharmacodynamic Study of ALX148 in Combination With Enfortumab Vedotin and/or Other Anticancer Therapies in Subjects With Urothelial Carcinoma (ASPEN-07)

• Histologically confirmed unresectable locally advanced or metastatic urothelial carcinoma. Subjects with urothelial carcinoma with squamous differentiation or mixed cell types are eligible provided that urothelial is the dominant histology.  Any element of neuroendocrine or small cell histology are excluded
• Must have received prior treatment with a immune checkpoint inhibitor in the locally advanced or metastatic setting
• Must have received prior treatment with platinum containing chemotherapy defined as received in the adjuvant/neoadjuvant setting with recurrent or progressive disease within 12 months of completion OR received treatment with platinum in the locally advanced or metastatic setting
• Must have had progression or recurrence during or following recept of most recent therapy
• ECOG PS 0-1
• Dose escalation cohorts must have available archival or fresh biopsy sample prior to study entry.  Others must have tumor accfessible for sequential biopsy and be willing to provide fresh pre-treatment and on-study tumor tissue biopsies
• No pre-existing sensory or motor neuropathy Grade >/= 2
• No symptomatic or unctrolled CNS metastases
• No prior treatment with enfortumab vedotin
• No prior treatment with any anti-CD47 or anti-SIRPa agent
• No known uncontrolled HBV/HCV/HIV
• No other malignancy within 3 years
• No active autoimmune disease requiring treatment in last year

• Primary
  • Safety and tolerability
  • MTD and RP2D
• Secondary
  • Overall safety profile
  • PK
  • Immunogenicity
  • Evidence of antitumor activity