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NCT07217171PHASE1Recruiting

A Study Evaluating the Safety, Efficacy, and Pharmacokinetics (PK) of EVOLVE104 in Participants With Advanced Urothelial and Squamous Cell Carcinomas

EvolveImmune United, Inc

Start Date

11/13/2025

Completion Date

1/29/2031

Summary

The goal of this study is to evaluate the safety and effectiveness of EVOLVE104 in participants with advanced urothelial and squamous cell carcinomas who have previously taken standard treatment options, have declined or have been ineligible for treatment with these medications. Participants with advanced or metastatic cancer who meet all eligibility criteria may be eligible to participate in the study.

Detailed Description

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

EVOLVE104

DRUG

EVOLVE104

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Conditions

Bladder CancerSquamous Cell Carcinoma of the LungEsophageal Squamous Cell CarcinomaTongue Squamous Cell CarcinomaCutaneous Squamous Cell CancerPenile Squamous Cell CarcinomaAnal Squamous Cell CarcinomaVulvar Squamous Cell CarcinomaCervical Squamous Cell CarcinomaVaginal Squamous Cell CarcinomaUrethral Squamous Cell Carcinoma

Locations

City of Hope

Duarte, California 91010

United States

USC/Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Yale University Cancer Center

New Haven, Connecticut 06511

United States

The Winship Cancer Institute Emory University

Atlanta, Georgia 30322

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

Columbia University Irving Medical Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania 19107

United States

SCRI

Nashville, Tennessee 37203

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Virginia Cancer Specialists

Fairfax, Virginia 22031

United States