INDP-D101 is a Phase 1/2, open-label, multi-center, dose escalation and expansion study evaluating the safety, tolerability and clinical activity of Decoy20 as monotherapy and in combination with tislelizumab in patients with locally advanced or metastatic solid tumors.
Decoy20, is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy. INDP-D101 is a Phase 1/2, open-label, multi-center, 3+3 dose escalation and expansion study evaluating the safety, tolerability and clinical activity of Decoy20 in subjects with advanced solid tumors. The study will include 2 parts: In Part 1, Subjects will receive a single dose of Decoy20 at one of up to three assigned dose levels on Week 1 Day 1 (SAD). Subjects will be observed for 28 days for dose limiting toxicity. Safety will be assessed by a safety review committee (SRC), comprised of investigators and the study sponsor, and subsequently will recommend the dose of Decoy20 to take forward. Part 2 began when a single dose recommended from Part 1 was identified to confirm the safety of weekly administration of Decoy20 in approximately 54 to 90 subjects. More than one dose may be studied in Part 2 that is at or below the MTD determined in Part 1. Eligible subjects must have one of the following locally advanced or metastatic tumor types: hepatocellular carcinoma (HCC), colorectal cancer (CRC) with liver metastasis, urothelial cancer, squamous cell carcinoma of the head and neck (SCCHN), adenocarcinoma of the pancreas, non-small cell lung cancer (NSCLC). Part 2 is further divided into 3 parts a Safety Run-In (Part 2a), a Dose Expansion (Part 2b) and a Combination with a PD-1 inhibitor, tislelizumab (Part 2c). Part 2a enrolls 6 subjects in a staggered manner, and each subject receives 4 weekly doses of Decoy20 identified in Part 1. Safety data for each of these subjects is collected for 4 weeks after the subjects' 4th Decoy20 dose for acute and delayed toxicity. This data is reviewed by the SRC and a determination of one or more tolerable doses of Decoy20 for Part 2b is made. Part 2b further evaluates and confirms the safety and preliminary efficacy of continuous weekly Decoy20 administration for up to 1 year. The SRC continues to meet and reviews data on an ongoing or ad-hoc basis during Part 2b of the study to ensure that there are no undue risks to study subjects and to confirm one or more tolerable doses for Phase 2. Part 2c will evaluate the safety and tolerability of Decoy20 in combination with tislelizumab. The SRC will continue to meet and review data on an ongoing or ad-hoc basis during Part 2c of the study to ensure that there are no undue risks to study subjects and to confirm one or more tolerable Phase 2 doses and sequencing.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
120
Decoy20 is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy.
Tislelizumab is a PD-1 inhibitor.
University of Southern California- Norris Cancer Center
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
The Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Washington University, Siteman Cancer Center
St Louis, Missouri, United States
Atlantic Health System
Morristown, New Jersey, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Gabrail Cancer & Research Center
Canton, Ohio, United States
UH Seidman Cancer Center
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
...and 2 more locations
Number of Subjects with dose-limiting toxicities (DLTs)
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medication. The relatedness and severity of treatment emergent adverse events will utilize the National Cancer Institute Common Toxicity Criteria for adverse events (NCI-CTCAE) for assessment.
Time frame: Through study completion, up to 3 years
Percentage of subjects with Adverse Events (AEs)
The count and percentage of subjects with AEs and Treatment Emergent Adverse Events (TEAEs) will be assessed for all subjects.
Time frame: Through completion, up to 3 years
Maximum Tolerated Dose (MTD) of Decoy20
The MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences Dose Limiting Toxicity during the first 28 days after dosing of Decoy20.
Time frame: Up to 2 years
Recommended Phase 2 Dose (RP2D) of Decoy20
The highest dose level that is declared to be safe and tolerable by the investigators and the sponsor.
Time frame: Up to 2.5 years
Anti-Drug Antibodies (ADA)
The incidence of ADAs will be assessed.
Time frame: Up to 3 years
Neutralizing Antibodies (NAbs)
The incidence of antibodies neutralizing Decoy20 will be assessed
Time frame: Up to 3 years
Maximum drug concentration (Cmax) of Decoy20
The blood pharmacokinetic parameter, Cmax, will be assessed pre-dose and up to 28 days post-dose after administration of Decoy20.
Time frame: Up to 3 years
Area under the concentration versus time curve (AUC) of Decoy20
The blood pharmacokinetic parameter, AUC, will be assessed pre-dose and up to 28 days post-dose after administration of Decoy20.
Time frame: Up to 3 years
Elimination half-life (t1/2) of Decoy20
The blood pharmacokinetic parameter, t1/2, will be assessed pre-dose and up to 28 days post-dose after administration of Decoy20.
Time frame: Up to 3 years
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects achieving a best overall response of confirmed Partial Response (PR) or Complete Response (CR), per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time frame: Up to 3 years
Duration of Response (DoR)
DoR is defined as the duration of time from date of first response to date of disease progression, as per RECIST v1.1
Time frame: Up to 3 years
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