Clinical trial NCT04903873: A Study to Evaluate Safety, Efficacy, and Pharmacokinetics in Participants With Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Renal Cell Cancer Metastatic
Non-Small Cell Lung Cancer
Renal Cell Carcinoma
Prostate Cancer
Keywords: Renal Cell Carcinoma
Prostate Cancer
Dose Escalation
Maximum tolerated dose
Lead sponsor: Eutilex
Sponsor class: INDUSTRY
First posted: 2021-05-27
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility 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. Also includes patients who cannot be treated with standard therapy because of underlying/existing medical condition.
* 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
* Phase 2: At least 1 measurable lesion per RECIST version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2
* Adequate organ and bone marrow function (Hemoglobin \>9.0 g/dL, Absolute neutrophil count ≥1,500/μL, Absolute lymphocyte count ≥600 and ≤2,500/μL, Platelet count ≥100,000/μL, Total bilirubin ≤1.5 × upper limit of normal, Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN, Serum creatinine ≤1.5 × ULN or creatinine clearance \>30 mL/min, Prothrombin time and activated partial thromboplastin time ≤1.5 × ULN)
* Life expectancy of at least 12 weeks
* Voluntarily provided a written consent to participate in the study
* Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days before study drug administration
* WOCBP and sexually active fertile male patients with partners who are WOCBP must agree to use 2 highly effective methods of contraception throughout the course of the study and for 12 weeks after the last dose of study drug.

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. Untreated but asymptomatic and clinically stable brain metastases per investigator's discretion 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
* Active infection that is not controlled or requires intravenous antibiotics in the last 2 weeks
* History of allogeneic tissue or organ transplant
* Active hepatitis B virus or hepatitis C virus infection
* History of any noninfectious hepatitis
* Human immunodeficiency virus (HIV) infection
* Received or receiving systemic corticosteroid therapy or any other form of systemic immunosuppressive medicaion 1 week before first dose of EU101
* Known severe (≥Grade 3) hypersensitivity reactions to antibody, or severe reaction to immuno-oncology agents requiring treatment with steroids
* Konwn or suspected hypersensitivity to EU101 or any component of its formulation
* Current or history of interstitial lung disease, anaphylaxis, uncontrolled asthma, or pneumonitis that has required systemic corticosteroids
* Patients with second primary cancer
* Clinically significant concurrent cardiovascular disease
* Pregnant women, breasfeeding women, WOCBP, or men with partners who are WOCBP who do not agree to use adequate contraceptive measures
* Determined as unable to participate in the study per investigator's judgment

Other protocol defined Inclusion/Exclusion criteria may apply

Primary outcomes:
measure: Phase 1: Number of Participants With Adverse Event (AEs) and Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation
timeFrame: Baseline up to 30 months
measure: Phase 1: Number of Participants With Dose Limiting Toxicity (DLT)
timeFrame: At the end of Cycle 1 (Each cycle is of 21 Days)
measure: Phase 1: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: Baseline up to 24 months
measure: Phase 1: Number of Participants With Clinically Significant Abnormalities in Vital Signs
timeFrame: Baseline up to 24 months
measure: Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examination
timeFrame: Baseline up to 24 months
measure: Phase 1: Number of Participants With Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG)
timeFrame: Baseline up to 24 months
measure: Phase 2: Objective Response Rate (ORR)
timeFrame: 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)
Secondary outcomes:
measure: Phase 1: Objective Response Rate (ORR)
timeFrame: 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)
measure: Phase 1 and 2: Duration of Response (DOR)
timeFrame: 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)
measure: Phase 1 and 2: Disease Control Rate (DCR)
timeFrame: 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)
measure: Phase 1 and 2: Time to Response (TTR)
timeFrame: 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)
measure: Phase 1 and 2: Time to Progression (TTP)
timeFrame: 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)
measure: Phase 1 and 2: Durable Clinical Benefit (DCB)
timeFrame: 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)
measure: Phase 1 and 2: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Phase 1 and 2: Overall survival (OS)
timeFrame: 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)
measure: Phase 1 and 2: Maximum Observed Serum Concentration (Cmax) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Trough Serum Concentration (Ctrough) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Elimination Half-Life Time (T1/2) of EU101
timeFrame: 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)]
measure: Phase 1 and 2: Apparent Volume of Distribution (Vd/F) of EU101
timeFrame: Baseline (Day 1)
measure: Phase 1 and 2: Apparent Oral Clearance of (CL/F) of EU101
timeFrame: Baseline (Day 1)
measure: Phase 1 and 2: Mean Residence Time (MRT) of EU101
timeFrame: Baseline (Day 1)
measure: Phase 1 and 2: Renal clearance (CLr) of EU101
timeFrame: Baseline (Day 1)
measure: Phase 1 and 2: Number of Participants with Positive Antidrug Antibodies (ADA)
timeFrame: Baseline up to 56 months
measure: Phase 2: Number of Participants With AEs and SAEs by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
timeFrame: Time from first dose of study treatment up to 30 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Mary Crowley Center
state: Texas
city: Ilsan
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Samsung Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Asan
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
Study officials:
References: