A Study to Evaluate ELU001 in Patients With Solid Tumors That Overexpress Folate Receptor Alpha (FRα)

Overview

About this study

The primary purpose of Part 1 (dose escalation) of this study is to establish the MTD and/or RP2D of ELU001 in subjects who have advanced, recurrent or refractory FRα overexpressing tumors considered to be topoisomerase 1 inhibitor-sensitive.

The primary purpose of Part 2 (Tumor Group Expansion Cohorts) of this study is to evaluate anti-tumor activity of ELU001 in subjects who have moderate or high FRα overexpressing tumors considered to be topoisomerase 1 inhibitor-sensitive.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

​​​​​Inclusion Criteria:

  • Male or female subjects aged 18 or older at the time of signed informed consent.
  • In the opinion of the Investigator, there is no other meaningful life-prolonging therapy option available.
  • Population:
    • Part 1: Must have documented diagnosis of ovarian cancer, endometrial cancer, colorectal cancer, gastric cancer, gastroesophageal junction cancer, triple negative breast cancer, non-small cell lung cancer, or cholangiocarcinoma.
    • Part 2 Stage 1: Must have one of the following cancer types indicated below with the corresponding expression level of FRα.:
    • Ovarian Cancer
      • Moderate and/or High
    • Endometrial Cancer
      • Moderate and/or High
    • Colorectal Cancer
      • Moderate and/or High
    • Gastric Cancer
      • Moderate and/or High
    • Gastroesophageal Junction Cancer
      • Moderate and/or High
    • Triple Negative Breast Cancer
      • Moderate and/or High
    • Non-small cell lung cancer
      • Moderate and/or High
    • Cholangiocarcinoma
      • Moderate and/or High
    • Specific cancer types from the table above will be selected by the Sponsor, in consultation with the Part 1 CSRC and other experts, at the conclusion of Part 1 Dose Escalation. In addition, moderate and high FRα expression thresholds will be defined and communicated by the Sponsor to Investigators upon completion of translational testing prior to the start of Part 2.

Part 2 Stage 2 or Registration Study:

  • Must have documented FRα expression in one of the topoisomerase 1 inhibitor-sensitive tumor types evaluated in Part 2 Stage 1. Specific tumor groups will be selected by the Sponsor, in consultation with the CSRC and/or Steering Committee (SC) and other experts, at the conclusion of Part 2 Stage 1.
  • Folate receptor α (FRα) expression:
    • Part 1: Must provide archival tumor tissue or a newly obtained tumor biopsy specimen prior to the first dose of study drug for retrospective FRα expression analysis. The availability of the FRα expression result is not required to start study drug administration.
    • Part 2: Must provide archival tissue or a newly obtained tumor biopsy specimen prior to the first dose of study drug for prospective determination of FRα overexpression at the Sponsor-designated laboratory. The FRα expression result is required prior to the initiation of study drug administration.
  • In Part 1, measurable disease or, in the absence of measurable disease, non-measurable disease (lesions considered truly non-measurable include leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal masses/abdominal organomegaly identified by physical exam that is not measurable by reproducible imaging techniques), as per RECIST v1.1. In Part 2, measurable disease (only), as per RECIST v1.1.
    • Note:  A lytic or mixed lytic-blastic bone lesion with a soft tissue component assessed on CT/MRI can be measurable if the minimum size criteria are met.
  • For other criteria, refer to RECIST v1.1.
  • Expected survival of at least 3 months.
  • In Part 1, Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or 2.
  • In Part 2, ECOG Performance Status of 0 or 1.
  • Adequate organ function defined as:
    • Absolute neutrophil count ≥ 1,500/μL;
    • Platelets ≥ 100,000/μL;
    • Hemoglobin ≥ 8 g/dL;
    • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (including subjects with documented Gilberts syndrome, liver metastases, or other etiologies);
    • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 5 x ULN;
    • Calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation.
  • Recovered from any previous surgery and no history of major surgery within the last 28 days prior to start of study drug.
  • For women of childbearing potential, willingness to avoid pregnancy by using an effective method of contraception from the first dose of ELU001 up to 5 times the half-life of ELU001 treatment (about 10 days) plus 6 months after the last dose of study drug (or longer, if required by Regulatory Authority or local practice).
  • For males who are capable of fathering a child, willingness to take precautions that are effective in preventing pregnancy from the first dose of ELU001 and up to 5 times the half-life of ELU001 treatment (about 10 days) plus 3 months after the last dose of study drug (or longer, if required by Regulatory Authority or local practice).
  • Willing and able to understand and comply with all aspects of the protocol.
  • Provided informed consent prior to any protocol-related procedures, including screening evaluations.

Exclusion Criteria:

  • Clinically significant active or chronic corneal disorder.
  • Prior treatment with folate receptor-targeting anti-cancer agent(s), or received investigational anti-cancer treatment ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, prior to starting study drug, whichever is shorter.
  • Require use of folate-containing supplements during the treatment period.
  • Known medical history of:
    • Clinically significant cardiovascular and respiratory conditions including myocardial infarction within 1 year, uncontrolled or unstable angina, congestive heart failure (New York Heart Association [NYHA] Class III or IV), or arrhythmia (Grade 2 or higher), within 5 years;
    • Another malignancy within 3 years before the first dose, or previously diagnosed with another malignancy, and have any evidence of residual disease. Subjects with non-melanoma skin cancer or cervix carcinoma in situ, treated and radiated early prostate cancer if they have undergone complete resection, or chronic lymphocytic leukemia (CLL) who is on close monitoring and treatment is not required, are not excluded;
    • Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment;
    • Serious, uncontrolled medical disorder such as seizures, nonmalignant systemic disease, or active, uncontrolled infection or active infection causing fever. Examples include, but are not limited to, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. Subjects with chronic diseases that are well controlled (e.g., diabetes mellitus, hypertension (< 150 systolic blood pressure [sBP] and < 90 diastolic blood pressure [BP]) are eligible;
    • Part 1 only: Recognized immunodeficiency condition including cellular immunodeficiencies, hypogammaglobulinemia or dysgammaglobulinemia; subjects who have hereditary, or congenital immunodeficiency’s (human immunodeficiency virus (HIV) infection, see below).
  • Any of the following conditions (testing is not required in this protocol, unless required by Regulatory Authority or local practice)
    • Known HIV-infected subjects, unless on effective anti-retroviral therapy with an undetectable viral load within 6 months; or
    • Known or suspected hepatitis B if active infection (subjects with chronic hepatitis B infection must have an undetectable Hepatitis B Virus (HBV) viral load on suppressive therapy, if indicated; positive surface antibody alone is not an exclusion); or
    • Known or suspected hepatitis C infection which has not been treated and cured unless currently on treatment with an undetectable viral load.
  • Active medical conditions of:
    • Subjects in Part 1 with autoimmune disease (e.g., rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), ulcerative colitis, Crohn's Disease, Multiple Sclerosis (MS), ankylosing spondylitis, thyroiditis) requiring continuing immune suppressive therapy;
    • Subjects in Part 1 with brain or leptomeningeal metastases; in Part 2, subjects with symptomatic brain or leptomeningeal metastases with any lesion greater than 3 cm, or evidence of herniation or hemorrhage.
  • Any of the following recent treatments or therapies:
    • Subject has received a transfusion (platelets or red blood cells) ≤ 2 weeks prior to first dose of study drug;
    • Chronic therapeutic corticosteroid use, defined as > 5 days of prednisone or equivalent in Part 1, except for inhalers or those on a pre-planned steroid taper.
    • Note: Premedication with corticosteroids to prevent or decrease the severity of infusion related reactions per institutional standard of care is allowed;
    • Chronically treated with systemic doses of other immunosuppressive drugs such as cyclosporine, methotrexate, adrenocorticotropic hormone (ACTH) or immune suppressive monoclonal antibodies.
  • Female subjects who are lactating or breast feeding or have a positive pregnancy test within 7 days prior to first dose of study drug.
  • Any condition(s) that, in the opinion of the Investigator, would increase the risk for toxicities from study drug, interfere with subject compliance or conduct of this study.
  • In the opinion of the Investigator, there is significant risk to a subject when the tumor tissue biopsy specimen procedure is performed
  • Subjects who have a QTcF > 470 ms within 4 weeks prior to the first dose of study drug.

Eligibility last updated 1/20/22. Questions regarding updates should be directed to the study team contact.

 

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Yujie Zhao, M.D., Ph.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Wen Wee Ma, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Tanios Bekaii-Saab, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

  • Promising targeted treatments and immunotherapy strategies in oncology and advancements in our understanding of molecular pathways that underpin cancer development have reignited interest in the tumor-associated antigen Folate Receptor alpha (FRα). FRα is a glycosylphosphatidylinositol (GPI)-anchored membrane protein. Its overexpression in tumors such as ovarian, breast and lung cancers, low and restricted distribution in normal tissues, alongside emerging insights into tumor-promoting functions and association of expression with patient prognosis, together render FRα an attractive therapeutic target. In this review, we summarize the role of FRα in cancer development, we consider FRα as a potential diagnostic and prognostic tool, and we discuss different targeted treatment approaches with a specific focus on monoclonal antibodies. Renewed attention to FRα may point to novel individualized treatment approaches to improve the clinical management of patient groups that do not adequately benefit from current conventional therapies. Read More on PubMed
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CLS-20523168

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