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
Description
Brief Summary
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 locally
advanced or metastatic solid tumors.
Detailed Description
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 seven 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 will begin when the single dose recommended from Part 1 is identified and it will
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 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 1 year. 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.
Phase
N/AInclusion and Exclusion Criteria
- Males or females, age 18 years or older.
- Histologically confirmed diagnosis of locally advanced or metastatic solid tumor. For Part 2, 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).
- Subject must have exhausted all available therapy or have declined treatment or treatment is contraindicated. Subjects with tumors that have known actionable molecular alteration such as EGFR, ALK, ROS-1, BRAF, RET, MET, and KRAS must have progressed on directed molecular therapy.
- 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.
- Willing and able to comply with all scheduled visits, laboratory tests, and other study procedures including mandatory pre-treatment and on-treatment biopsies for subjects enrolled to Part2.
- Pregnant or lactating females.
- Has an active systemic (viral, bacterial, or fungal) infection or requiring treatment.
- Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Received prior chemotherapy, targeted therapy or immunotherapy within 28 days or 5 half-lives from W1D1, whichever is shorter.
- 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 or subjects with diagnosis of a new thrombotic event within 90 days prior to Decoy20 dosing,.
- 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) and other indolent malignancies will be allowed after discussion with the Sponsor).
- 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.
- 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 14 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, vaso-vagal sensitivity, 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 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.
Sites
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.
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