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RecruitingInterventionalPhase 1

A Phase 1 Dose-Escalation and Expansion Study of Intratumorally Administered ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas

NCT ID: NCT06022029Sponsor: OncoNano Medicine, Inc.Last updated: 2025-12-24

Summary

A phase 1, multicenter, open label, non-randomized dose escalation and dose expansion study to examine the maximum tolerated dose, (MTD), minimum effective dose (MED) and/or recommended dose for expansion (RDE) of intratumoral ONM-501 as monotherapy and in combination with a PD-1 checkpoint inhibitor in patients with advanced solid tumors and lymphomas.

Detailed description

This Phase 1, multi-center trial will consist of three parts: monotherapy dose escalation; combination therapy dose finding; and combination therapy dose expansion exploring two doses in specific tumor indication(s). Each dosing cycle of ONM-501 will be 21 days. ONM 501 will be administered as intratumoral injections once per week for three weeks (on Days 1, 8, and 15), followed by three weeks without ONM-501 administration. The monotherapy dose escalation will utilize an accelerated titration method. The combination agent will be administered according to standard protocol, once every three weeks. This phase will evaluate ONM-501 in combination with approved immune checkpoint inhibitor (ICI) cemiplimab. Enrollment in this phase will follow a "Rolling 6" or 6+0 methodology - up to 6 patients will be enrolled in a staggered format; dose escalation of ONM-501 will be permitted. Once the recommended doses for expansion (RDEs) are determined for ONM-501 + ICI combination or ONM-501 monotherapy, the expansion phase of this study will be initiated. The expansion phase will enroll patients in one to three indication-specific expansion cohorts.

Arms & interventions

  • DrugONM-501

    Intratumoral injection

  • DrugCemiplimab

    Intravenous administration of 350 mg

Outcome measures

Primary

  • Dose Escalation and Expansion Phases: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity

    AE incidence will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. AE severity will be graded according to NCI CTCAE version 5.0 or later. Grade 1 scales as Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 scales as Moderate (minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living \[ADL\]); Grade 3 scales as Severe (severe or medically significant but not immediately life threatening hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 scales as Life-threatening consequences, urgent intervention indicated, and Grade 5 scales as Death related to Adverse Event (AE)

    Time frame: Up to approximately 24 months

  • Dose Escalation and Expansion Phases: Number of Participants with Dose-Limiting Toxicities (DLTs)

    DLT will be defined as the occurrence of any of the following events in the first 28 days of treatment in the dose escalation cohorts in Part 1 of the study or in the first 28 days of treatment for the first 6 patients at any dose in Part 1b (DLT observation periods). Any adverse event resulting in a dose hold or delay of ≥ 28 days will be considered a DLT. Toxicity will be evaluated according to NCI CTCAE version 5.0.

    Time frame: Up to approximately 24 months

  • Dose Escalation and Expansion Phases: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)

    AE incidence will be coded using Medical Dictionary for Regulatory Activities (MedDRA) terminology. AE severity will be graded according to NCI CTCAE version 5.0 or later.

    Time frame: Up to approximately 24 months

Secondary

  • Dose Escalation and Expansion Phases: Cmax

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Dose Escalation and Expansion Phases: t1/2z

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Dose Escalation and Expansion Phases: Tmax

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Dose Escalation and Expansion Phases: AUCt

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Dose Escalation and Expansion Phases: AUCinf

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Dose Escalation and Expansion Phases: CL/F

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Dose Escalation and Expansion Phases: Vz/F

    Time frame: Dose Escalation and Expansion Phases: Cycle 1 Day 1 and Cycle 1 Day 8 (each cycle is 21 days): predose and at multiple timepoints (up to 24 hours).

  • Expansion Phase Only: Objective Response Rate (ORR)

    Time frame: Up to approximately 24 months

  • Expansion Phase Only: Duration of Response (DOR)

    Time frame: Up to approximately 24 months

  • Expansion Phase Only: Progression-Free Survival (PFS)

    Time frame: Up to approximately 24 months

  • Expansion Phase Only: Overall Survival (OS)

    Time frame: Up to approximately 24 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1. Ability to understand and willingness to sign written informed consent before performance of any study procedures 2. Age ≥ 18 years 3. Participants with solid tumors or lymphomas, confirmed by available histopathology records or current biopsy, that are advanced, nonresectable, or recurrent and progressing since last antitumor therapy, and for which no alternative standard therapy exists. 4. Participants must have a minimum of one injectable and measurable lesion. 5. Participants with prior Hepatitis B or C are eligible if they have adequate liver function 6. Participants with human immunodeficiency virus (HIV) are eligible if on established HAART for a minimum of 4 weeks prior to enrollment, have an HIV viral load \<400 copies/mL, and have CD4+ T-cell (CD4+) counts ≥ 350 cells/uL 7. Adequate bone marrow function: 8. Adequate liver function Exclusion Criteria: Patients will be excluded from this study if they meet any of the following criteria (Part 1a and Part 1b). 1. Other malignancy active within the previous 2 years except for basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast that has completed curative therapy. 2. Major surgery within 4 weeks before the first dose of study drug. 3. Brain metastases that are untreated or in the posterior fossa or involve the meninges. Participants with stable or previously treated progressing brain metastases (except in the posterior fossa or involving the meninges) may be permitted in a case-by-case basis at the Sponsor's discretion. 4. Prolongation of corrected QT (QTc) interval to \>470 millisecond (ms) for males and females when electrolytes balance is normal. 5. Females who are breastfeeding or pregnant at screening or baseline 6. Females of childbearing potential that refuse to use a highly effective method of contraception. 7. Has uncontrolled or poorly controlled hypertension as defined by a sustained BP \> 9. Has received prior investigational therapy within 5 half-lives of the agent or 4 weeks before the first administration of study drug, whichever is shorter. 8. Has had any major cardiovascular event within 6 months prior to study drug 10. Has known hypersensitivity to any component in the formulation of ONM-501 9. Has an active infection requiring systemic treatment 10. Is participating in another therapeutic clinical trial Additional Exclusion Criteria for ONM-501 in Combination with cemiplimab (Part 1b) 1. Has known hypersensitivity to any component in the formulation of cemiplimab 2. Has any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\>10 mg daily prednisone equivalent) 3. Has a condition requiring systemic treatment with corticosteroids

Study locations (9)

California Research Institute

Los Angeles, California, 90027

Active Not Recruiting

BRCR Global

Tamarac, Florida, 33321

Withdrawn

Gabrail Cancer Center Research

Canton, Ohio, 44718

Completed

Ohio State University

Columbus, Ohio, 43210

Completed

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224

Completed

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

Completed

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

Completed

MD Anderson Cancer Center

Houston, Texas, 77030

Active Not Recruiting

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031

Completed