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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
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/exclusion criteria may apply
Primary outcome measure(s)
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
Trial sites (11)
Facility
City
Region
Status
DFCI
Boston
Massachusetts
Not Yet Recruiting
Sarah Cannon Research Institute 335 24th Avenue North, Suite 400
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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