Clinical trial NCT06022029: A Dose Escalation and Dose Expansion Study of Intratumoral ONM-501 Alone and in Combination With Cemiplimab in Patients With Advanced Solid Tumors and Lymphomas.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Triple Negative Breast Cancer
Diffuse Large B Cell Lymphoma
Follicular Lymphoma
Lymphoma, Non-Hodgkin
Mantle Cell Lymphoma
Bladder Cancer
Uveal Melanoma, Recurrent
Cervix Cancer
Carcinoma in Situ
Head and Neck Squamous Cell Carcinoma
Skin Cancer
Metastatic Cancer
Tumor, Solid
Tumor Recurrence
Keywords: Solid tumors
Lymphoma
ONM-501
STING
Intra-tumoral
HNSCC
Breast Cancer
Melanoma
Skin Cancer
cemiplimab
Libtayo
DLBCL
bladder cancer
cervical cancer
metastases
immunotherapy
ICI
TNBC
Triple Negative
mTNBC
anti-PD-1 antibody
BRCA1
BRCA2
anti-PD-L1
uveal
NHL
Mantle Zone lymphoma
FL
stimulator of interferon genes
Lead sponsor: OncoNano Medicine, Inc.
Sponsor class: INDUSTRY
First posted: 2023-09-01
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: In Part 1a patients will receive ONM-501 as a single agent; in Part 1b patients will receive ONM-501 in combination with Cemiplimab; Part 2 will be an expansion of ONM-501 in combination with Cemiplimab.
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose Escalation and Expansion Phases: Number of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs) and Based on TEAEs Severity
timeFrame: Up to approximately 24 months
measure: Dose Escalation and Expansion Phases: Number of Participants with Dose-Limiting Toxicities (DLTs)
timeFrame: Up to approximately 24 months
measure: Dose Escalation and Expansion Phases: Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAEs)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Dose Escalation and Expansion Phases: Cmax
timeFrame: 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).
measure: Dose Escalation and Expansion Phases: t1/2z
timeFrame: 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).
measure: Dose Escalation and Expansion Phases: Tmax
timeFrame: 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).
measure: Dose Escalation and Expansion Phases: AUCt
timeFrame: 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).
measure: Dose Escalation and Expansion Phases: AUCinf
timeFrame: 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).
measure: Dose Escalation and Expansion Phases: CL/F
timeFrame: 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).
measure: Dose Escalation and Expansion Phases: Vz/F
timeFrame: 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).
measure: Expansion Phase Only: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Expansion Phase Only: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Expansion Phase Only: Progression-Free Survival (PFS)
timeFrame: Up to approximately 24 months
measure: Expansion Phase Only: Overall Survival (OS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: Tamarac
country: United States
facility: BRCR Global
state: Florida
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Cancer Care Wollongong
state: New South Wales
city: Buderim
country: Australia
facility: University of the Sunshine Coast Clinical Trials
state: Queensland
city: Southport
country: Australia
facility: Tasman Oncology Research
state: Queensland
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
Study officials:
References: