Bladder CancerPhase 1NCT07217171
A Study Evaluating the Safety, Efficacy, and Pharmacokinetics (PK) of EVOLVE104 in Participants With Advanced Urothelial and Squamous Cell Carcinomas
A Phase 1 study testing EVOLVE104 in people with Bladder Cancer and Squamous Cell Carcinoma of the Lung, run by EvolveImmune United, Inc at 16 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer, Squamous Cell Carcinoma of the Lung, Esophageal Squamous Cell Carcinoma
- What is being tested?
- EVOLVE104
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 16 sitesUnited States
- Study dates
- 13 Nov 2025to 29 Jan 2031
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
16 sites in 1 country. Contact the study team or a site near you to ask about taking part.
16 sites in 1 country
United States16 sites, 16 recruiting
- Recruiting
The Winship Cancer Institute Emory University
Atlanta, Georgia, 30322
alejandra.maria.bono@emory.edu
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Megan.Boland@UHhospitals.org
- Recruiting
City of Hope
Duarte, California, 91010
mkilgore@coh.org
- Recruiting
Duke University Medical Center - Duke Cancer Center
Durham, North Carolina, 27710
Nikkia.brown@duke.edu
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
skamal@nextoncology.com
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
colleen.armstrong@startresearch.com
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
GIclinicaltrials@mdanderson.org
- Recruiting
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Stephanie.kim2@med.usc.edu
- Recruiting
SCRI
Nashville, Tennessee, 37203
Meghan.McGuire@scri.com
- Recruiting
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232
rebekah.caza@vumc.org
- Recruiting
Yale University Cancer Center
New Haven, Connecticut, 06511
alicia.appiah-chin@yale.edu
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
joseph.watters@mssm.edu
- Recruiting
Columbia University Irving Medical Center
New York, New York, 10032
jk4704@cumc.columbia.edu
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
iyerg@mskcc.org
- Recruiting
Thomas Jefferson University, Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania, 19107
Adjoa.Ntoso@jefferson.edu
- Recruiting
UCSF Medical center Parnassus
San Francisco, California, 94158
HDFCCC.CIRCT@ucsf.edu
About this study
Official title: 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
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.
Read the 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.
- 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
- Being tested
- EVOLVE104
- Keywords
- bladder, lung, esophagus, tongue, penile, anal, vulvar, cervical, vaginal
- Medical subject headings
- Urinary Bladder Neoplasms, Esophageal Squamous Cell Carcinoma, Anus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EVOLVE104Drug
EVOLVE104 is provided as a solution for injection via IV infusion
EVOLVE104Drug
Dose levels for Phase 1b will be determined based on the outcome of Phase 1a
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a Cohort 1; dose level 1 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 2; dose level 2 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 3; dose level 3 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 4; dose level 4 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 5; dose level 5 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 6; dose level 6 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 7; dose level 7 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 8; dose level 8 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 9; dose level 9 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1a Cohort 10; dose level 10 | Experimental | Active Study Drug Receives: Drug: EVOLVE104 |
| Phase 1b Cohort 1; dose level TBD | Experimental | Active study drug Receives: Drug: EVOLVE104 |
| Phase 1b Cohort 2; dose level TBD | Experimental | Active study drug Receives: Drug: EVOLVE104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Efficacy will be evaluated through analysis of the overall response rate (ORR), including rates of complete response (CR), partial response (PR); and duration of response (DOR), and disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Measured: Baseline, through study completion, an average of 10 months.
Evaluate the Cmax of EVOLVE104
The maximum observed plasma concentration will be evaluated.
Measured: 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
The duration of time taken to reach Cmax will be evaluated.
Measured: 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
AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated.
Measured: 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
The presence of ADAs and their clinical impact will be assessed
Measured: Collected pre-dose cycle 1 and then every other cycle starting with cycle 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2025
- Study start13 Nov 2025
- Primary completion29 Jan 2029 (estimated)
- Study completion29 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- EvolveImmune United, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- EvolveImmune Study Team, Study director, EvolveImmune United, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07217171
- Sponsor's protocol ID
- EIU-104101
- Status last verified
- Sep 2026
- First submitted
- 10 Oct 2025
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No