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A Study to Evaluate Safety, Efficacy, and Pharmacokinetics in Participants With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04903873
Recruitment Status : Recruiting
First Posted : May 27, 2021
Last Update Posted : November 15, 2021
Sponsor:
Information provided by (Responsible Party):
Eutilex

Brief Summary:
Phase 1 (Dose Escalation) of this study will assess the safety, tolerability, dose-limiting toxicity (DLT), and will determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of EU101 in participants with advanced solid tumors. Phase 2 (Dose Expansion) of the study will assess the antitumor effect of EU101 in two indications including colorectal cancer (CRC) and non-small cell lung cancer (NSCLC).

Condition or disease Intervention/treatment Phase
Solid Tumor Colorectal Neoplasms Non-Small Cell Lung Cancer Drug: EU101 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1/2 Study to Evaluate Safety, Efficacy, and Pharmacokinetics of EU101, an Agonistic Anti-CD137 (4-1BB) Monoclonal Antibody in Patients With Advanced Solid Tumors
Actual Study Start Date : May 31, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: EU101: Dose Escalation Cohort
Participants with advanced solid tumors will receive EU101 intravenously once every 3 weeks (3 weeks = 1 cycle) with escalating doses starting from 0.05 milligrams per kilogram (mg/kg) to 10 mg/kg until disease progression, unacceptable toxicities or death, withdrawal of consent, end of study, or physician's decision, whichever occurs first.
Drug: EU101
EU101 will be administered via intravenous infusion.

Experimental: EU101: Dose Expansion Cohort 1
Participants with CRC will receive EU101 intravenously once every 3 weeks (3 weeks = 1 cycle) with a determined recommended phase 2 dose until disease progression, unacceptable toxicities or death, withdrawal of consent, end of study, or physician's decision, whichever occurs first.
Drug: EU101
EU101 will be administered via intravenous infusion.

Experimental: EU101: Dose Expansion Cohort 2
Participants with NSCLC will receive EU101 intravenously once every 3 weeks (3 weeks = 1 cycle) with a determined recommended phase 2 dose until disease progression, unacceptable toxicities or death, withdrawal of consent, end of study, or physician's decision, whichever occurs first.
Drug: EU101
EU101 will be administered via intravenous infusion.




Primary Outcome Measures :
  1. Phase 1: Number of Participants With Adverse Event (AEs) and Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation [ Time Frame: Baseline up to 30 months ]
  2. Phase 1: Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: At the end of Cycle 1 (Each cycle is of 21 Days) ]
  3. Phase 1: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters [ Time Frame: Baseline up to 24 months ]
    Laboratory assessments include hematology, serum chemistry, other blood tests, coagulation, and urine analysis. Number of participants with clinically significant abnormalities will be reported.

  4. Phase 1: Number of Participants With Clinically Significant Abnormalities in Vital Signs [ Time Frame: Baseline up to 24 months ]
    Vital signs will include body temperature, pulse rate, and systolic and diastolic blood pressure measurements. Number of participants with clinically significant abnormalities will be reported.

  5. Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examination [ Time Frame: Baseline up to 24 months ]
    Physical examination will include head, eyes, ears, nose and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and musculoskeletal systems. Number of participants with clinically significant abnormalities will be reported.

  6. Phase 1: Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) [ Time Frame: Baseline up to 24 months ]
    ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Number of participants with clinically significant abnormalities will be reported.

  7. Phase 2: Objective Response Rate (ORR) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 24 months) ]
    Objective response rate (ORR), defined as the percentage of participants with a best overall response (BOR) of either a complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors by investigators.


Secondary Outcome Measures :
  1. Phase 1: Objective Response Rate (ORR) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 24 months) ]
    Objective response rate (ORR), defined as the percentage of participants with a BOR of either a complete response (CR) or partial response (PR), per RECIST version 1.1 for solid tumors by investigators.

  2. Phase 1 and 2: Duration of Response (DOR) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
  3. Phase 1 and 2: Disease Control Rate (DCR) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
    DCR will be defined similarly to ORR but also including stable disease (SD) in the categorization of response (i.e, RECIST response of either CR, PR, or SD).

  4. Phase 1 and 2: Time to Response (TTR) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
  5. Phase 1 and 2: Time to Progression (TTP) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
  6. Phase 1 and 2: Durable Clinical Benefit (DCB) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
    DCB will be defined similarly to DCR but additionally specifying that the disease control be achieved for at least 12 weeks consecutive (i.e, RECIST response of CR, PR or SD for greater than or equal to [>=] 12 weeks consecutive).

  7. Phase 1 and 2: Progression-Free Survival (PFS) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
  8. Phase 1 and 2: Overall survival (OS) [ Time Frame: Time from first dose of study treatment assessed until disease progression, death, withdrawal of consent, physician's decision, start of new anticancer therapy, or end of study, whichever occurs first (approximately for 56 months) ]
  9. Phase 1 and 2: Maximum Observed Serum Concentration (Cmax) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    Cmax is defined as maximum observed serum concentration.

  10. Phase 1 and 2: Trough Serum Concentration (Ctrough) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    Ctrough is steady-state pre-dose concentration.

  11. Phase 1 and 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    Tmax is defined as time to reach maximum observed serum concentration.

  12. Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    AUC0-24 is defined as the area under the serum concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24).

  13. Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    AUC0-last is defined as area under the serum concentration time-curve from time zero to the time of last measured concentration.

  14. Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    AUCinf is defined as area under the serum concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

  15. Phase 1 and 2: Elimination Half-Life Time (T1/2) of EU101 [ Time Frame: Cycle 1: Pre-dose up to 336 hours post-dose; Cycle 2: 504 hours post-dose; Cycle 3: Pre-dose (Each cycle is of 21 days)] ]
    T1/2 is defined as plasma decay half-life is the time measured for the serum concentration to decrease by one half.

  16. Phase 1 and 2: Apparent Volume of Distribution (Vd/F) of EU101 [ Time Frame: Baseline (Day 1) ]
    Vd/F is defined as volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.

  17. Phase 1 and 2: Apparent Oral Clearance of (CL/F) of EU101 [ Time Frame: Baseline (Day 1) ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

  18. Phase 1 and 2: Mean Residence Time (MRT) of EU101 [ Time Frame: Baseline (Day 1) ]
    MRT is defined as AUMC(0 - inf) divided by AUC(0 - inf), where AUMC(0 - inf) is the area under the first moment curve from time 0 extrapolated to infinite time.

  19. Phase 1 and 2: Renal clearance (CLr) of EU101 [ Time Frame: Baseline (Day 1) ]
    CLr is defined as renal clearance is the volume of plasma completely cleared of EU101 by the kidneys per unit time.

  20. Phase 1 and 2: Number of Participants with Positive Antidrug Antibodies (ADA) [ Time Frame: Baseline up to 56 months ]
    The immunogenic potential of EU101 will be assessed by summarizing the number of participants who develop detectable antidrug antibody (ADAs).

  21. Phase 2: Number of Participants With AEs and SAEs by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 [ Time Frame: Time from first dose of study treatment up to 30 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of metastatic or locally advanced solid tumors for which no standard therapy exists or standard therapy has failed because of disease progression or unacceptable toxicities.
  • Cohort 1 (colorectal cancer): a) CRC (including microsatellite instability-high [MSI-H] and microsatellite-stable [MSS]) regardless of RAS mutation. b) Disease progression within 3 months after last administration of approved standard therapies. c) Prior cytotoxic chemotherapy for metastatic disease include all the following agents: fluoropyrimidine, oxaliplatin, and irinotecan
  • Adjuvant chemotherapy-based treatments count as prior therapy, as long as relapse had occurred within 6 months of completion of such therapies, prior anti-epidermal growth factor receptor (EGFR) therapy (cetuximab, panitumumab), anti-angiogenic therapy (bevacizumab, aflibercept, ramucirumab), regorafenib, and TAS-102 are allowed. d) No more than 5 prior therapies for metastatic disease. For participants who had disease recurrence within 6 months of completing adjuvant chemotherapy, the adjuvant regimen can be considered as 1 chemotherapy regimen for metastatic disease
  • Cohort 2 (NSCLC): a) NSCLC without known EGFR, anaplastic lymphoma kinase (ALK), and ROS1 genomic tumor aberrations. b) No standard therapy exists or standard therapy has failed. c) No more than 3 prior therapies for metastatic disease

Key Exclusion Criteria:

  • Primary central nervous system (CNS) tumor (Phase 1), CNS metastasis, and/or carcinomatous meningitis. Participants with prior brain metastases treated at least 4 weeks before the first dose of EU101 that are clinically stable and do not require chronic corticosteroid treatment are allowed
  • Received prior therapy with any anti-CD137 monoclonal antibody (mAb) or agent
  • Major surgery requiring general anesthesia within 3 weeks before first dose of EU101 or still recovering from prior surgery
  • History of allogeneic tissue or organ transplant
  • Human immunodeficiency virus (HIV) infection
  • Active hepatitis B virus or hepatitis C virus infection
  • Current or history of interstitial lung disease, anaphylaxis, uncontrolled asthma, or pneumonitis that has required systemic corticosteroids

Other protocol defined Inclusion/Exclusion criteria may apply


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04903873


Contacts
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Contact: Kyung Hye Kim 82220713324 Kyunghye.kim@eutilex.com

Locations
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United States, Texas
Mary Crowley Center Recruiting
Dallas, Texas, United States, 75230
Contact: Minal Barve, MD         
Korea, Republic of
National Cancer Center Not yet recruiting
Ilsan, Korea, Republic of
Contact: Tak Yun, MD, PhD         
Samsung Seoul Hospital Recruiting
Seoul, Korea, Republic of
Contact: Myung-Ju Ahn, MD, PhD         
Seoul Asan Recruiting
Seoul, Korea, Republic of
Contact: Tae Won Kim, MD, PhD         
Sub-Investigator: Sang-we Kim, MD, PhD         
Sub-Investigator: Shin-kyo Yoon, MD, PhD         
Sub-Investigator: Dae-ho Lee, MD, PhD         
Sponsors and Collaborators
Eutilex
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Responsible Party: Eutilex
ClinicalTrials.gov Identifier: NCT04903873    
Other Study ID Numbers: EU-CTS101-I-01
First Posted: May 27, 2021    Key Record Dates
Last Update Posted: November 15, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eutilex:
Colorectal cancer
Non-small cell lung cancer
Dose Escalation
Maximum tolerated dose
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases