Advanced Solid Tumor
Conditions
Brief summary
The study will be conducted in 2 phases: Phase 1: Dose-escalation and Dose Level Expansion, Phase 1 will determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). Phase 2: Tumor-Specific Expansions with Dose Optimization, Phase 2 will further evaluate CLIO-8221 in tumor-specific expansion cohorts to optimize dosing and assess preliminary efficacy.
Detailed description
Phase 1: Dose-escalation and Dose Level Expansion. Dose escalation safety data will be reviewed by a Safety Monitoring Committee (SMC) to guide dosing decisions. Backfill enrollment may be used to further characterize safety, PK/PD, and antitumor activity. Phase 2: Tumor-Specific Expansions with Dose Optimization. Phase 2 will further evaluate CLIO-8221 in tumor-specific expansion cohorts to optimize dosing and assess preliminary efficacy. Safety, tolerability, PK/PD, and response data will support selection of the recommended Phase 2 dose (RP2D) for further development.
Interventions
DRUGCLIO-8221
intravenous (IV) infusion
Sponsors
Callio Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
No, this is an open-label trial
Intervention model description
Phase 1: no randomization will be performed. Phase 2: participants in each cohort will be randomized with a 1:1 ratio to receive one of the expansion doses of CLIO-8221.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with advanced solid tumors * Patients must have metastatic or unresectable disease not suitable for further local treatment and should have received prior beneficial therapies unless ineligible, unwilling, or lacking access. * LVEF ≥50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan. * An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 * Measurable disease per RECIST version 1.1 at baseline
Exclusion criteria
* Prior anti-tumor treatment with an ATRi. * Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), including, but not limited to, adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, and Stage I uterine cancer. * History of uncontrolled seizure disorders or clinically significant neurodegenerative disorders, including progressive peripheral neuropathy. Stable Grade ≤ 2 peripheral neuropathy is allowed. * Clinically significant autoimmune disease, either currently present or present within the previous 2 years, including a current requirement for systemic immunosuppressive therapy equivalent to \>10 mg/prednisone daily (local immunosuppressive therapy such as inhaled or topical corticosteroids is allowed). * Any uncontrolled Grade ≥ 3 (per NCI CTCAE version 6.0) viral, bacterial, or fungal infection within 2 weeks prior to Cycle 1 Day 1. Routine antimicrobial prophylaxis is permitted. * History of hepatic cirrhosis, autoimmune hepatitis, or drug-associated hepatitis within the past 12 months. * Uncontrolled diabetes mellitus, defined as Hgb A1c ≥8% or Hgb A1c between 7% and \<8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained. * Any other medical, social, or psychosocial factors that, in the opinion of the investigator, could impact safety or compliance with study procedures. Additional protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Type, incidence, severity, and seriousness of adverse events (AEs) | Through end of treatment, up to approximately 2 years. | Type, incidence, severity, and seriousness of AEs occurred |
| Type, incidence, and severity of laboratory abnormalities | Through end of treatment, up to approximately 2 years. | Type, incidence, and severity of laboratory abnormalities occurred |
| Incidence of dose limiting toxicities dose (RP2D) of CLIO-8221 | From first dose through study day 21. | Incidence of dose limiting toxicities occurred |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Through disease progression, up to approximately 2 years. | Participants who achieve partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria |
| Disease control rate | Through disease progression, up to approximately 2 years. | Participants who achieve stable disease, partial or complete response per RECIST v1.1 criteria |
| Progression-free survival | Up to approximately 2 years. | Time from first dose of CLIO-8221 to disease progression or death, whichever occurs first |
| Duration of objective response | From the date of enrollment until a confirmed partial or complete response is achieved, assessed up to 2 years. | Time from the first documented objective tumor response (complete or partial), subsequently confirmed, to radiographic progression or death |
| Pharmacokinetic Parameter Area Under the Curve (AUC) for CLIO-8221 | Varying timepoints through end of treatment, up to approximately 2 years. | Measure of CLIO-8221 AUC in plasma |
| Pharmacokinetic Parameter Maximum Concentration (Cmax) for CLIO-8221 | Varying timepoints through end of treatment, up to approximately 2 years. | Measure of CLIO-8221 Cmax in plasma |
| Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for CLIO-8221 | Varying timepoints through end of treatment, up to approximately 2 years. | Measure of CLIO-8221 Tmax in plasma |
| Pharmacokinetic Parameter Total Clearance (CL) for CLIO-8221 | Varying timepoints through end of treatment, up to approximately 2 years. | Measure of CLIO-8221 CL in plasma |
| Pharmacokinetic Parameter Volume of distribution at steady state (Vd) for CLIO-8221 | Varying timepoints through end of treatment, up to approximately 2 years. | Measure of CLIO-8221 Vd in plasma |
| Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for CLIO-8221 | Varying timepoints through end of treatment, up to approximately 2 years. | Measure of CLIO-8221 t1/2 in plasma |
Countries
Australia, United States
Contacts
CONTACTCMO
Outcome results
None listed