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.
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.
Eligibility
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
