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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGThe Winship Cancer Institute Emory University
Atlanta, Georgia, United States
RECRUITINGSTART Midwest
Grand Rapids, Michigan, United States
RECRUITINGSCRI
Nashville, Tennessee, United States
RECRUITINGVirginia Cancer Specialists
Fairfax, Virginia, United States
RECRUITINGIncidence 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.
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)
Time frame: Baseline, through study completion, an average of 10 months.
Evaluate the Cmax of EVOLVE104
The maximum observed plasma concentration will be evaluated.
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
The duration of time taken to reach Cmax will be evaluated.
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
AUC time curve from 0 to 24 hrs post dose and percent difference between intervals will be evaluated.
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
The presence of ADAs and their clinical impact will be assessed
Time frame: Collected pre-dose cycle 1 and then every other cycle starting with cycle 4
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