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

NCT07217171 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: EIU-104101
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Esophageal Squamous Cell Carcinoma; Tongue Squamous Cell Carcinoma; Cutaneous Squamous Cell Cancer; Penile Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Vulvar Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Vaginal Squamous Cell Carcinoma; Urethral Squamous Cell Carcinoma; Bladder Cancer; Squamous Cell Carcinoma of the Lung

Keywords

bladder; lung; esophagus; tongue; penile; anal; vulvar; cervical; vaginal

Outcome Measures

Primary Outcomes (4)

• Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)

  TEAEs will be assessed during routine study visits and compared to Baseline to continuously evaluate safety and tolerability

  Baseline, through study completion, an average of 10 months.

• Number of patients with Dose Limiting Toxicities (DLTs)

  Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals.

  Baseline, through study completion, an average of 10 months.

• To determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) for EVOLVE104

  Safety evaluations will occur consistently for each subject and across patients to assess MTD or RDE. Evaluations include analysis of TEAEs as well as ongoing assessments of laboratories, ECGs and physical examinations.

  Baseline, through study completion, an average of 10 months.

• To determine the recommended phase 2 dose (RP2D) of EVOLVE104

  Selection of the RP2D will be based on the aggregate safety, efficacy, PK, and PD observations for the entire study

  Safety evaluations will be done as described above. PK and PD to be done each cycle (28 days) at pre-dose and post dose starting Day 1 at various time points, dependent upon treatment regimen assigned, through study completion, an average of 10 months.

Secondary Outcomes (5)

• Assess the efficacy of EVOLVE104

  Baseline, through study completion, an average of 10 months.

• Evaluate the Cmax of EVOLVE104

  PK and PD to be done each cycle (28 days) at pre-dose and post dose starting Day 1 at various time points, dependent upon treatment regimen assigned, through study completion, an average of 10 months.

• Evaluate the Tmax of EVOLVE104

  PK and PD to be done each cycle (28 days) at pre-dose and post dose starting Day 1 at various time points, dependent upon treatment regimen assigned, through study completion, an average of 10 months.

• Evaluate the Area Under the Curve (AUC) for EVOLVE104

  PK and PD to be done each cycle (28 days) at pre-dose and post dose starting Day 1 at various time points, dependent upon treatment regimen assigned, through study completion, an average of 10 months.

• Evaluate the incidence of anti-drug antibodies (ADA) to EVOLVE104

  Collected pre-dose cycle 1 and then every other cycle starting with cycle 4

Study Arms (12)

Phase 1a Cohort 1; dose level 1

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 2; dose level 2

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 3; dose level 3

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 4; dose level 4

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 5; dose level 5

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 6; dose level 6

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 7; dose level 7

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 8; dose level 8

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 9; dose level 9

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1a Cohort 10; dose level 10

EXPERIMENTAL

Active Study Drug

Drug: EVOLVE104

Phase 1b Cohort 1; dose level TBD

EXPERIMENTAL

Active study drug

Drug: EVOLVE104

Phase 1b Cohort 2; dose level TBD

EXPERIMENTAL

Active study drug

Drug: EVOLVE104

Interventions

EVOLVE104 DRUG

EVOLVE104 is provided as a solution for injection via IV infusion

Phase 1a Cohort 10; dose level 10; Phase 1a Cohort 1; dose level 1; Phase 1a Cohort 2; dose level 2; Phase 1a Cohort 3; dose level 3; Phase 1a Cohort 4; dose level 4; Phase 1a Cohort 5; dose level 5; Phase 1a Cohort 6; dose level 6; Phase 1a Cohort 7; dose level 7; Phase 1a Cohort 8; dose level 8; Phase 1a Cohort 9; dose level 9

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Participant must have documented disease progression during or post treatment with standard of care, dependent upon tumor type.
• The cancer must be measurable by CT scan or MRI.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤1.
• Anticipated life expectancy of at least 3 months.
• Adequate organ function, as indicated by standard blood tests.
• Able to provide a fresh or archival tumor biopsy.
• 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.

You may not qualify if:

• The participant is a candidate for treatment with a targeted agent known to provide a benefit.
• Persistent significant toxicities from prior anticancer therapy.
• Brain metastases unless previously treated and stable.
• Prior severe or life-threatening immunologic reactions to previous therapies.
• 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.

Sponsors & Collaborators

• EvolveImmune United, Inc: lead

Study Sites (10)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Yale University Cancer Center

New Haven, Connecticut, 06511, United States

RECRUITING

The Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

SCRI

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Esophageal Squamous Cell Carcinoma; Anus Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Officials

• EvolveImmune Study Team

  EvolveImmune United, Inc

  STUDY DIRECTOR

Central Study Contacts

Evolve Study Team

CONTACT

12032086584; Evolve104Study@evolveimmune.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1a of the study includes up to 10 participant groups given escalating dose levels of EVOLVE104 until the maximum tolerated dose(s) are reached. A Safety Review Committee will convene to review safety data from each cohort prior to dosing the next highest dose level. Phase 1b of the study will enroll two expansion cohorts, participants in each cohort will receive one of the selected doses from Phase 1a that may be opened at the Sponsors discretion depending on the outcome of Phase 1a. One or more doses or dose regimens of EVOLVE104 may be recommended.

Study Record Dates

• First Submitted: October 10, 2025
• First Posted: October 15, 2025
• Study Start: November 13, 2025
• Primary Completion (Estimated): January 29, 2029
• Study Completion (Estimated): January 29, 2031
• Last Updated: June 3, 2026

Record last verified: 2026-06

Locations

US (10)