DECOY20 Study in Patients With Advanced Solid Tumors

Solid Tumor, Adult Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05651022
• Other study ID #: INDP-D101
• Status: Recruiting
• Phase: Phase 1
• Start date: February 28, 2023
• Est. completion date: April 30, 2025

Study information

• Verified date: January 2024
• Source: Indaptus Therapeutics, Inc
• Contact: Indaptus Therapeutics
• Phone: 1-800-208-3508
• Email: D101[@]indaptusrx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 30, 2025
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males or females, age 18 years or older.

2. 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).

3. 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.

4. Measurable disease (at least 1 measurable lesion) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as defined by tumor type.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Life expectancy of at least 3 months.

7. 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.

8. Male subjects must utilize reliable contraceptive precautions for the duration of Decoy20 treatment and 30 days after the last dose of Decoy20.

9. Adequate organ function as demonstrated by baseline laboratory assessment

10. Left ventricular ejection fraction (LVEF) = 45% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA).

11. Recovered from toxicities due to prior therapies.

12. 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.

Exclusion Criteria:

1. Pregnant or lactating females.

2. Has an active systemic (viral, bacterial, or fungal) infection or requiring treatment.

3. 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.

4. Received prior chemotherapy, targeted therapy or immunotherapy within 28 days or 5 half-lives from W1D1, whichever is shorter.

5. 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).

6. 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).

7. 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,.

8. 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).

9. 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.

10. Has a history of known genetic predisposition to HLH/MAS.

11. 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.

12. Has received a live vaccine within 14 days of W1D1

13. Has active autoimmune disease.

14. Has a history of significant CNS disease, such as stroke or uncontrolled and unstable epilepsy.

15. Has severe pulmonary interstitial disease and/or oxygen saturation on room air < 92%.

16. Baseline Q-T correlated (QTc) interval of > 470 msec for females and > 450 msec for males calculated using Fridericia's formula.

17. 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.

18. Major surgical procedure within 4 weeks prior to first dose of Decoy20, or anticipation of need for a major surgical procedure, during the study.

19. Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or Decoy20 administration.

20. Has received investigational therapy within 28 days or 5 half-lives of the start of study drug.

21. Unwillingness or inability to comply with procedures required in this protocol.

22. Known allergy or hypersensitivity to Decoy20 or one of the ingredients of Decoy20.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• Decoy20
Decoy20 is a novel, systemically administered multiple Toll-like receptor (TLR) agonist-based cancer immunotherapy.

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Gabrail Cancer & Research Center	Canton	Ohio
United States	The Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	University of Southern California- Norris Cancer Center	Los Angeles	California
United States	Atlantic Health System	Morristown	New Jersey
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California

Sponsors (2)

Lead Sponsor	Collaborator
Indaptus Therapeutics, Inc	Translational Drug Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Anti-Drug Antibodies (ADA)	The incidence of ADAs will be assessed.	Up to 3 years
Secondary	Neutralizing Antibodies (NAbs)	The incidence of antibodies neutralizing Decoy20 will be assessed	Up to 3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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