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

EvolveImmune United, Inc

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: EVOLVE104

Study type: Interventional

Funder types: Industry

Identifiers

NCT07217171

EIU-104101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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160 participants in 12 patient groups

Phase 1a Cohort 1; dose level 1

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 2; dose level 2

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 3; dose level 3

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 4; dose level 4

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 5; dose level 5

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 6; dose level 6

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 7; dose level 7

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 8; dose level 8

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 9; dose level 9

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1a Cohort 10; dose level 10

Experimental group

Description:

Active Study Drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1b Cohort 1; dose level TBD

Experimental group

Description:

Active study drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104

Phase 1b Cohort 2; dose level TBD

Experimental group

Description:

Active study drug

Treatment:

Drug: EVOLVE104

Drug: EVOLVE104