DECOY20 Study in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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INDP-D101 is a Phase 1, open-label, multi-center, dose escalation and expansion study evaluating the safety, tolerability and clinical activity of Decoy20 in patients with advanced solid tumors.

Detailed Description
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Decoy20, is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy. INDP-D101 is a Phase 1, 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 3 parts: In Part 1, Subjects will receive a single dose of Decoy20 at one of up to four 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 Decoy 20 to take forward. Part 2 will begin when the single dose recommended from Part 1 is identified and it will confirm the safety of weekly administration of Decoy 20 in approximately 20 subjects. Part 2 is further divided into 2 parts a Safety Run-In (Part 2a) and a Dose Expansion (Part 2b). Part 2a will enroll 6 subjects in a staggered manner, and each subject will receive 4 weekly doses of Decoy20 identified in Part 1. Safety data for each of these subjects will be collected for 4 weeks after the subjects' 4th Decoy20 dose for acute and delayed toxicity. This data will be reviewed by the SRC and the determination of the Decoy20 dose for Part 2b made. Part 2b will further evaluate and confirm the safety and preliminary efficacy of continuous weekly Decoy20 administration for up to 2 years. The SRC will continue to meet and review 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 the RP2D and regimen.

Official Title
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A Phase 1, Open-Label, Multi-Center, Dose Escalation and Expansion Study Evaluating the Safety, Tolerability and Clinical Activity of DECOY20 in Patients With Advanced Solid Tumors

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: Decoy20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females, age 18 years or older. Histologically confirmed diagnosis of an advanced metastatic solid tumor. Subject has received at least 1 and up to 3 lines of prior therapy in the metastatic setting, and then progressed (recurred, relapsed or are refractory) or has been intolerant. Measurable disease (at least 1 measurable lesion) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as defined by tumor type. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy of at least 3 months. Female subjects must be of non-childbearing potential (surgically sterile or at least 2 years postmenopausal) or agree to use a highly effective contraception method while receiving treatment with Decoy20 and for 30 days after the last dose of Decoy20. Male subjects must utilize reliable contraceptive precautions for the duration of Decoy20 treatment and 30 days after the last dose of Decoy20. Adequate organ function as demonstrated by baseline laboratory assessment Left ventricular ejection fraction (LVEF) ≥ 45% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA). Recovered from toxicities due to prior therapies. Exclusion Criteria: Pregnant or lactating females. Has an active systemic (viral, bacterial, or fungal) infection or requiring treatment. Received radiotherapy within 28 days of the first dose of Decoy20. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Received prior chemotherapy, immunotherapy, or major immunomodulatory therapy within 28 days or 5 half-lives from W1D1. If prior treatment with a programed cell death 1 (PD-1) or programed cell death ligand 1 (PD-L1) inhibitor within 2 months prior to eligibility. Received systemic corticosteroid therapy > 5 mg/day of prednisone or equivalent dose of another corticosteroid within 1 week or 5 half-lives (whichever is shorter) from the start of study drug or is expected to require it during the course of the study (topical and inhaled steroids are permitted). Has radiographically detected primary central nervous system (CNS) metastases or symptomatic CNS involvement (including leptomeningeal carcinomatosis, cranial neuropathies or mass lesions that cause spinal cord compression). Clinical evidence of significant coagulopathy during Screening (e.g., deep vein thrombosis or pulmonary embolism) or history of significant uncontrolled coagulopathy. Has an active secondary malignancy in addition to the primary, excluding low-risk neoplasms as determined by the Investigator (e.g., non-metastatic basal cell or squamous cell skin carcinoma). Has a history of or active infection with Human Immunodeficiency Virus 1 or 2, positive read for Hepatitis B virus antibodies or surface antigen or positive read for Hepatitis C ribonucleic acid detected by qualitative assay. Known intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Has a history of known genetic predisposition to HLH/MAS. Has undergone splenectomy, has an active chronic liver disease, alcoholic liver disease, Wilson's disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, history of or planned liver transplant for end-stage liver disease of any etiology, documented history of advanced liver fibrosis or history of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy, or variceal bleeding. Has received a live vaccine within 28 days of W1D1. Has active autoimmune disease. Has a history of significant CNS disease, such as stroke or uncontrolled and unstable epilepsy. Has severe pulmonary interstitial disease and/or oxygen saturation on room air < 92%. Baseline Q-T correlated (QTc) interval of > 470 msec for females and > 450 msec for males calculated using Fridericia's formula. New York Heart Association Class III or IV cardiac disease, or myocardial ischemia or infarction within 180 days of Screening, severe unstable angina, coronary/peripheral artery bypass graft, worsening/decompensated heart failure within the past 6 months, or any other clinically significant cardiac abnormality that, in the judgement of the I Investigator, would pose a health risk to the subject. Major surgical procedure within 4 weeks prior to first dose of Decoy20, or anticipation of need for a major surgical procedure, during the study. Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or Decoy20 administration. Has received investigational therapy within 28 days or 5 half-lives of the start of study drug. Unwillingness or inability to comply with procedures required in this protocol. Known allergy or hypersensitivity to Decoy20 or one of the ingredients of Decoy20.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects will receive a single dose of Decoy20 at one of up to four assigned dose levels on Week 1 Day 1. Subjects will be observed for 28 days for dose limiting toxicity in the single ascending dose Part 1.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>A single dose of Decoy20 at a dose of 7 x 10^7 Killed Bacteria (KB) | Drug: Decoy20<br>* Decoy20 is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy.<br>|
| Experimental: Cohort 2<br>A single dose of Decoy20 at a dose of 20 x 10^7 KB | Drug: Decoy20<br>* Decoy20 is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy.<br>|
| Experimental: Cohort 3<br>A single dose of Decoy20 at a dose of 70 x 10^7 KB | Drug: Decoy20<br>* Decoy20 is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy.<br>|
| Experimental: Cohort 4<br>A single dose of Decoy20 at a dose of 200 x 10^7 KB | Drug: Decoy20<br>* Decoy20 is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | Up to 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Drug Antibodies (ADA) | The incidence of ADAs will be assessed. | Up to 3 years | 
| Neutralizing Antibodies (NAbs) | The incidence of antibodies neutralizing Decoy20 will be assessed | 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. | 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. | 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. | 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) | 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 | Up to 3 years |