A Phase 1 Dose-Escalation and Expansion Study Evaluating the Safety, Efficacy, and Pharmacokinetics of EVOLVE104 in Subjects With Advanced Urothelial and Squamous Cell Carcinomas

This is a dose-escalation and expansion First in Human phase 1a/1b study evaluating safety, tolerability, and pharmacokinetics (PK) of EVOLVE104 in participants with advanced, relapsed or refractory solid tumors, including bladder, lung, esophageal, tongue, cutaneous and anogenital squamous cell carcinomas. This study consists of Phase 1a dose-escalation stage followed by a Phase 1b dose expansion stage featuring 2 expansion cohorts that may be opened, at the Sponsor's discretion, depending on the safety, efficacy, and other observations from Phase 1a.

This study is anticipated to enroll approximately 160 participants: up to 80 participants in Phase 1a, and up to 80 participants in Phase 1b.

Participants will be treated until they meet treatment discontinuation criteria, including disease progression, adverse events (AEs), subject decision, investigator decision, withdrawal of consent, death. The expected duration of treatment in this study is approximately 10 months based on the anticipated progression rates for the represented malignancies.

Key Inclusion Criteria:

Participants must have locally advanced or metastatic cancer with one of the following tumor types: bladder cancer, squamous cell carcinoma of the lung, esophagus, skin, or an anogenital squamous cell carcinoma.

1. Participant must have documented disease progression during or post treatment with standard of care, dependent upon tumor type.
2. The cancer must be measurable by CT scan or MRI.
3. Eastern Cooperative Oncology Group (ECOG) performance status score ≤1.
4. Anticipated life expectancy of at least 3 months.
5. Adequate organ function, as indicated by standard blood tests.
6. Able to provide a fresh or archival tumor biopsy.
7. Male and female participants must agree to use contraception during the study and for 120 days after the last dose of study drug, except for women who are post-menopausal or surgically sterile.

Key Exclusion Criteria:

1. The participant is a candidate for treatment with a targeted agent known to provide a benefit.
2. Persistent significant toxicities from prior anticancer therapy.
3. Brain metastases unless previously treated and stable.
4. Prior severe or life-threatening immunologic reactions to previous therapies.
5. Significant medical conditions, including but not limited to:
   • History of clinically significant cardiac disease
   • Severe esophageal disease such as esophageal rupture or severe erosive esophagitis.
   • Active inflammatory corneal or conjunctival inflammation, erosion, or ulcerations.
   • History of cirrhosis or significant portal hypertension.
   • Uncontrolled or significant infection.
   • History of certain other cancers in the past 3 years.
   • History of arterial thrombosis, stroke and transient ischemic attack within 6 months.
   • Active or uncontrolled HIV, HBV or HCV infection.
   • Autoimmune or other condition requiring chronic systemic immunosuppression.