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

Eutilex

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor; Renal Cell Cancer Metastatic; Renal Cell Carcinoma; Prostate Cancer; Non-Small Cell Lung Cancer

Treatments: Drug: EU101

Study type: Interventional

Funder types: Industry

Identifiers

NCT04903873

EU-CTS101-I-01

Details and patient eligibility

About

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).

Enrollment: 110 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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110 participants in 3 patient groups

EU101: Dose Escalation Cohort

Experimental group

Description:

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.

Treatment:

Drug: EU101

EU101: Dose Expansion Cohort 1

Experimental group

Description:

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.

Treatment:

Drug: EU101

EU101: Dose Expansion Cohort 2

Experimental group

Description:

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.

Treatment:

Drug: EU101