A Study of Evorpacept (ALX148) With Enfortumab Vedotin for Subjects With Urothelial Carcinoma (ASPEN-07)

Study Overview
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Brief Summary
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AT148007 is 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.

Official Title
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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)

Conditions
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Bladder Cancer, Urothelial Carcinoma

Intervention / Treatment
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* Drug: Evorpacept
* Drug: Enfortumab Vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, unresectable locally advanced or metastatic urothelial carcinoma. Must have received prior treatment with an immune checkpoint inhibitor (CPI). Subjects must have received prior treatment with platinum-containing chemotherapy. Subjects must have had progression or recurrence of urothelial cancer. Subjects must have measurable disease according to RECIST (Version 1.1). Adequate bone marrow function. Adequate renal function. Adequate liver function. Adequate Eastern Cooperative Oncology Group (ECOG) performance status. Exclusion Criteria: Preexisting sensory or motor neuropathy Grade ≥2. Presence of symptomatic or uncontrolled central nervous system (CNS) metastases. Prior treatment with enfortumab vedotin or other monomethylauristatin (MMAE)-based antibody-drug conjugate (ADCs) Prior treatment with any anti-CD47 or anti-signal regulatory protein-α (SIRPα) agent. Known active keratitis or corneal ulcerations. Subjects with superficial punctate keratitis are allowed if the disorder is being adequately treated. History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evorpacept (ALX148) + Enfortumab Vedotin<br>Phase 1a Dose Escalation: Evorpacept (ALX148) infusions will be administered every two weeks. Enfortumab vedotin will be administered at 1.25 mg/kg IV on Days 1, 8, and 15 of each 28-day cycle. | Drug: Evorpacept<br>* Fusion protein that blocks CD47-SIRPalpha pathway<br>* Other names: ALX148;Drug: Enfortumab Vedotin<br>* Nectin-4 directed antibody and microtubule inhibitor conjugate<br>* Other names: PADCEV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| First Cycle Dose limiting toxicities (DLTs) |  | Up to 28 days | 
| Adverse Events (AEs) as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0)), timing, seriousness, and relationship to study therapy |  | Up to 24 months |