Anal Squamous Cell Carcinoma, Bladder Cancer, Cervical Squamous Cell Carcinoma, Cutaneous Squamous Cell Cancer, Esophageal Squamous Cell Carcinoma, Penile Squamous Cell Carcinoma, Squamous Cell Carcinoma of the Lung, Tongue Squamous Cell Carcinoma, Urethral Squamous Cell Carcinoma, Vaginal Squamous Cell Carcinoma, Vulvar Squamous Cell Carcinoma
Conditions
Keywords
bladder, lung, esophagus, tongue, penile, anal, vulvar, cervical, vaginal
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.
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.
Interventions
DRUGEVOLVE104
EVOLVE104 is provided as a solution for injection via IV infusion
Sponsors
EvolveImmune United, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) | Baseline, through study completion, an average of 10 months. | TEAEs will be assessed during routine study visits and compared to Baseline to continuously evaluate safety and tolerability |
| Number of patients with Dose Limiting Toxicities (DLTs) | Baseline, through study completion, an average of 10 months. | Protocol-defined potential DLTs will be assessed by the Safety Review Committee at routine intervals. |
| To determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDEs) for EVOLVE104 | Baseline, through study completion, an average of 10 months. | 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. |
| To determine the recommended phase 2 dose (RP2D) of EVOLVE104 | 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. | Selection of the RP2D will be based on the aggregate safety, efficacy, PK, and PD observations for the entire study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess the efficacy of EVOLVE104 | Baseline, through study completion, an average of 10 months. | 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) |
| 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. | The maximum observed plasma concentration will be evaluated. |
| 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. | The duration of time taken to reach Cmax will be evaluated. |
| 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. | AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated. |
| Evaluate the incidence of anti-drug antibodies (ADA) to EVOLVE104 | Collected pre-dose cycle 1 and then every other cycle starting with cycle 4 | The presence of ADAs and their clinical impact will be assessed |
Countries
United States
Contacts
CONTACTEvolve Study Team
STUDY_DIRECTOREvolveImmune Study Team
EvolveImmune United, Inc
Outcome results
None listed