EVOLVE104 for advanced bladder and other squamous cell cancers

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 will try EVOLVE104, an experimental drug, in adults with advanced or metastatic bladder or other squamous cell cancers who have already tried or cannot take standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: EvolveImmune United, Inc (Industry-sponsored)
• Locations: 9 sites (Los Angeles, California and 8 other locations)
• Trial ID: NCT07217171 on ClinicalTrials.gov

What this trial studies

This first-in-human phase 1a/1b trial uses a dose-escalation stage followed by a dose-expansion stage to study safety, tolerability, and pharmacokinetics of EVOLVE104 in people with advanced, relapsed, or refractory urothelial and squamous cell carcinomas. Phase 1a will identify safe dose levels, and Phase 1b may open up to two expansion cohorts based on safety and early signals. The study plans to enroll about 160 participants across the two stages, treating participants until disease progression or other discontinuation criteria. Key procedures include imaging to document measurable disease and fresh or archival tumor biopsies for correlative testing.

Who should consider this trial

Good fit: Adults with advanced or metastatic bladder, lung, esophageal, tongue, cutaneous, or anogenital squamous cell carcinomas who have progressed on or are ineligible for standard treatments, have measurable disease, ECOG 0–1, adequate organ function, and can provide a tumor biopsy.

Not a fit: Patients who have effective targeted therapies available, poor organ function, ECOG >1, life expectancy under three months, or who cannot undergo required biopsies or travel to the study sites are unlikely to benefit.

Why it matters

Potential benefit: If successful, EVOLVE104 could provide a new treatment option for patients with few approved alternatives and potentially slow tumor growth.

How similar studies have performed: EVOLVE104 is being tested in humans for the first time and is therefore unproven in people, although other early-phase targeted or immunotherapy agents in these cancers have sometimes produced responses in phase 1.

Eligibility criteria

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.

Where this trial is running

Los Angeles, California and 8 other locations

• USC/Norris Comprehensive Cancer Center — Los Angeles, California, United States (Recruiting)
• Yale University Cancer Center — New Haven, Connecticut, United States (Recruiting)
• The Winship Cancer Institute Emory University — Atlanta, Georgia, United States (Recruiting)
• START Midwest — Grand Rapids, Michigan, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Thomas Jefferson University, Sidney Kimmel Cancer Center — Philadelphia, Pennsylvania, United States (Recruiting)
• Scri — Nashville, Tennessee, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Evolve Study Team

Conditions Bladder Cancer; Squamous Cell Carcinoma of the Lung; Esophageal Squamous Cell Carcinoma; Tongue Squamous Cell Carcinoma; Cutaneous Squamous Cell Cancer; Penile Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Vulvar Squamous Cell Carcinoma