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
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
Study locations (9)
California Research Institute
Los Angeles, California, 90027
BRCR Global
Tamarac, Florida, 33321
Gabrail Cancer Center Research
Canton, Ohio, 44718
Ohio State University
Columbus, Ohio, 43210
Allegheny Health Network
Pittsburgh, Pennsylvania, 15224
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
MD Anderson Cancer Center
Houston, Texas, 77030
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031