RecruitingInterventionalPhase 1

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

NCT ID: NCT07217171Sponsor: EvolveImmune United, IncLast updated: 2026-06-03

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.

Arms & interventions

DrugEVOLVE104
EVOLVE104 is provided as a solution for injection via IV infusion
DrugEVOLVE104
Dose levels for Phase 1b will be determined based on the outcome of Phase 1a

Outcome measures

Primary

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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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

Assess the efficacy of EVOLVE104
Time frame: Baseline, through study completion, an average of 10 months.
Evaluate the Cmax of EVOLVE104
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Collected pre-dose cycle 1 and then every other cycle starting with cycle 4

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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.