Study in Advanced Solid Tumor Patients

Official title

A Phase 1/2 Study of CLIO-8221 in Patients With Advanced Solid Tumors

Overview

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

• Drug CLIO-8221
  intravenous (IV) infusion

Primary outcome measures

• Type, incidence, severity, and seriousness of adverse events (AEs) [Time frame: Through end of treatment, up to approximately 2 years.]
• Type, incidence, and severity of laboratory abnormalities [Time frame: Through end of treatment, up to approximately 2 years.]
• Incidence of dose limiting toxicities dose (RP2D) of CLIO-8221 [Time frame: From first dose through study day 21.]

Secondary outcome measures (10)

• Objective Response Rate [Time frame: Through disease progression, up to approximately 2 years.]
• Disease control rate [Time frame: Through disease progression, up to approximately 2 years.]
• Progression-free survival [Time frame: Up to approximately 2 years.]
• Duration of objective response [Time frame: From the date of enrollment until a confirmed partial or complete response is achieved, assessed up to 2 years.]
• Pharmacokinetic Parameter Area Under the Curve (AUC) for CLIO-8221 [Time frame: Varying timepoints through end of treatment, up to approximately 2 years.]
• Pharmacokinetic Parameter Maximum Concentration (Cmax) for CLIO-8221 [Time frame: Varying timepoints through end of treatment, up to approximately 2 years.]
• Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) for CLIO-8221 [Time frame: Varying timepoints through end of treatment, up to approximately 2 years.]
• Pharmacokinetic Parameter Total Clearance (CL) for CLIO-8221 [Time frame: Varying timepoints through end of treatment, up to approximately 2 years.]
• Pharmacokinetic Parameter Volume of distribution at steady state (Vd) for CLIO-8221 [Time frame: Varying timepoints through end of treatment, up to approximately 2 years.]
• Pharmacokinetic Parameter Apparent Terminal Half-life (t1/2) for CLIO-8221 [Time frame: Varying timepoints through end of treatment, up to approximately 2 years.]

Eligibility criteria

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/exclusion criteria may apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 6 centers

• Scientia Clinical Research — Randwick
• Integrated Clinical Oncology Network Pty Ltd — South Brisbane
• Peter Maccallum Cancer Centre — Box Hill
• AlfredHealth — Heidelberg
• Royal Melbourne Hospital — Melbourne
• Linear Clinical Research Ltd — Nedlands

United States · 5 centers

• DFCI — Boston
• Sarah Cannon Research Institute 335 24th Avenue North, Suite 400 — Nashville
• MD Anderson Cancer Center — Houston
• START San Antonio — San Antonio
• START Mountain — West Valley City

Identifiers

NCT: NCT07300943 · CLIO-8221-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗