Clinical Trials /

Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

NCT04092673

Description:

This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of eFT226 in subjects with selected advanced solid tumor malignancies. The study will evaluate weekly 1-hour intravenous (IV) administration of eFT226. Treatment and study subject evaluations will be performed in 21 day cycles.

Related Conditions:
  • Malignant Solid Tumor
  • Pancreatic Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
  • Official Title: A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

Clinical Trial IDs

  • ORG STUDY ID: eFT226-0002
  • NCT ID: NCT04092673

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
eFT226selective translation inhibitorsequential escalation

Purpose

This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of eFT226 in subjects with selected advanced solid tumor malignancies. The study will evaluate weekly 1-hour intravenous (IV) administration of eFT226. Treatment and study subject evaluations will be performed in 21 day cycles.

Detailed Description

      Part 1 (dose escalation) will enroll subjects with an advanced solid tumor that is refractory
      or intolerant to standard of care therapy, where the tumor is pancreatic adenocarcinoma (no
      molecular typing) or any other solid tumor that has a documented activating mutation,
      amplification, or fusion of HER2, ERBB3, FGFR1, FGFR2, or an activating mutation in KRAS.

      Subjects will be assigned sequentially to increasing eFT226 doses. The starting dose of
      eFT226 is 0.005 mg/kg administered IV weekly in 21 day cycles. eFT226 doses will be escalated
      in subsequent cohorts after subjects enrolled in a given cohort have completed the 21-day
      dose-limiting toxicity (DLT) evaluation period. Dose escalation in Part 1 will enroll
      subjects based on 3+3 design, whereby 3 subjects will be initially enrolled and treated at
      each dose level.

      To obtain as robust a data set as possible regarding PK, safety and tolerability in a diverse
      population prior to selecting the RP2D, the MTD and MTD-1 cohorts may be backfilled up to 15
      subjects total in each cohort.

      Part 2 (Expansion Cohort) of the study will provide cohort expansion to further explore the
      safety, pharmacology, and clinical activity of eFT226 monotherapy in subjects with previously
      treated advanced solid tumor malignancies. Part 2 will be based on results observed in Part 1
      and will be defined by amendment to the protocol.
    

Trial Arms

NameTypeDescriptionInterventions
sequential escalationExperimentaleFT226 is administered IV weekly in 21 day cycles. eFT226 doses will be escalated in sequential cohorts after subjects enrolled in a given cohort have completed the 21-day dose-limiting toxicity (DLT) evaluation period. Starting dose is 0.005mg/kg/week, potentially escalating to 0.12mg/kg/week until MTD and RP2D are established
  • eFT226

Eligibility Criteria

        Inclusion Criteria:

          1. Part 1 (Dose Escalation): Subject has an advanced solid tumor that is refractory or
             intolerant to standard of care therapy, where the tumor is pancreatic adenocarcinoma
             (no molecular typing required) or any other solid tumor that has at least one of the
             following: a documented activating mutation, amplification, or fusion of HER2, ERBB3,
             FGFR1, FGFR2, or an activating mutation in KRAS; molecular tumor typing can be
             determined by immunohistochemistry (IHC; at IHC2+ or greater level), fluorescence in
             situ hybridization (FISH), next generation sequencing, or other analysis methods as
             appropriate. If the tumor is breast cancer or gastric cancer, subject must have failed
             treatment with trastuzumab as well as another anti-HER2 agent.

          2. Men and women of age ≥ 18 years

          3. Subject has a life expectancy of 3 months or more.

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

          5. Has at least 1 measurable lesion per RECIST Version 1.1 criteria.

          6. Completion of all previous therapy (including radiotherapy, chemotherapy,
             immunotherapy, or investigational therapy) for the treatment of cancer for 4 weeks (6
             weeks for nitrosourea or mitomycin) before the start of study therapy.

          7. All acute toxic effects of any prior antitumor therapy resolved to Grade 1 before the
             start of study therapy (with the exception of alopecia [Grade ≤ 2 permitted],
             neurotoxicity [Grade ≤ 2 permitted], or selected laboratory parameters [Grade ≤ 2
             permitted with exceptions as noted below])

          8. Adequate bone marrow function:

        8a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. 8b. Platelet count ≥ 100 × 109/L (Grade
        ≤ 1). 8c. Hemoglobin ≥ 9.0 g/dL (Grade ≤ 2) maintained for ≥ 2 weeks from any prior
        transfusion.

        9. Adequate hepatic function during Screening as defined below: 9a. Serum alanine
        aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤5 x ULN if known liver
        involvement.

        9b. Serum aspartate aminotransferase (AST) ≤ 3 x ULN or ≤ 5 x ULN if known liver
        involvement.

        9c. Serum bilirubin ≤ 1.5 x ULN (unless due to Gilbert's syndrome or hemolysis, in which
        case ≤ 3 x ULN is permitted).

        10. Adequate renal function: 10a. Measured or estimated creatinine clearance (eClCR) > 50
        mL/min (eClCR to be calculated by the Cockcroft-Gault formula 11. Adequate electrolyte
        values within 72 hours before the start of study therapy: 11a. Serum potassium within
        normal limits (WNL). 11b. Serum calcium (adjusted for serum albumin concentration) WNL.
        11c. Serum magnesium WNL. Note: Oral or IV supplementation or medical therapy may be used
        to achieve normal values for serum potassium, calcium and magnesium.

        12. Adequate coagulation profile: 12a. Prothrombin time (PT) ≤ 1.5 x ULN (Grade ≤ 1). 12b.
        Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (Grade ≤ 1).

        13. For female subjects of childbearing potential, a negative serum pregnancy test within 7
        days prior to start of study therapy.

        14. For female subjects of childbearing potential, willingness to use a
        protocol-recommended method of contraception from the start of the screening period until ≥
        30 days after the final dose of study therapy. Note: A female subject is considered to be
        of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or
        bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and
        follicle-stimulating hormone [FSH] levels within the institutional laboratory
        postmenopausal range and a negative serum or urine beta human chorionic gonadotropin
        [βHCG]); or is menopausal (age ≥ 55 years with amenorrhea for ≥ 6 months).

        15. For male subjects who can father a child and are having intercourse with females of
        childbearing potential who are not using adequate contraception, willingness to use a
        protocol-recommended method of contraception from the start of study therapy until ≥ 30
        days after the final dose of study therapy and to refrain from sperm donation from the
        start of study therapy until ≥ 90 days after administration of the final dose of study
        therapy. Note: A male subject is considered able to father a child unless he has had a
        bilateral vasectomy with documented aspermia or a bilateral orchiectomy.

        16. In the judgment of the Investigator, participation in the protocol offers an acceptable
        benefit-to-risk ratio when considering current disease status, medical condition, and the
        potential benefits and risks of alternative treatments for the subject's cancer.

        17. Willingness and ability to comply with scheduled visits, drug administration plan,
        protocol-specified laboratory tests, other study procedures, and study restrictions.

        Exclusion Criteria:

          1. History of another malignancy except for the following: adequately treated local basal
             cell or squamous cell carcinoma of the skin; adequately treated carcinoma in situ
             without evidence of disease; adequately treated papillary, noninvasive bladder cancer;
             other adequately treated Stage 1 or 2 cancers currently in complete remission; or any
             other cancer that has been in complete remission for ≥ 2 years.

          2. Previously documented or current brain metastases that have not been treated.

          3. Significant cardiovascular disease (eg, myocardial infarction, arterial
             thromboembolism, cerebrovascular thromboembolism) within 6 months prior to start of
             study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical
             therapy; unstable angina; symptomatic peripheral vascular disease; New York Heart
             Association Class 3 or 4 congestive heart failure; uncontrolled Grade ≥ 3 hypertension
             (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 160 mmHg) despite
             antihypertensive therapy; or history of congenital prolonged QT syndrome.

          4. Significant screening ECG abnormalities, including unstable cardiac arrhythmia
             requiring medication, left bundle branch block, 2nd degree atrioventricular (AV) block
             type II, 3rd degree AV block, Grade ≥ 2 bradycardia, or corrected QT (QTcF) > 450 msec
             (based on the average of 3 measurements at 5-minute intervals).

          5. Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper
             respiratory tract infections) at the time of start of study therapy. Note: Subjects
             with localized fungal infections of skin or nails are eligible.

          6. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency
             virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Note:
             Negative Hep B surface antigen and negative Hep B core antibody or undetectable Hep B
             virus DNA per qPCR testing; Negative Hep C virus antibody or negative HCV RNA by qPCR
             testing; Negative HIV antibody.

          7. Pregnancy or breastfeeding.

          8. Major surgery within 4 weeks before the start of study therapy or not fully recovered
             from major surgery.

          9. Prior solid organ transplantation.

         10. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids.
             Note: At screening, subjects may be using systemic corticosteroids (at doses of ≤ 10
             mg of prednisone or equivalent) or topical or inhaled corticosteroids. During study
             therapy, subjects may use systemic, enteric, topical or enteric corticosteroids as
             required for treatment-emergent conditions.

         11. Use of a known QT-prolonging drugs during screening or expected requirement for use
             during study therapy

         12. Use of a strong or moderate inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 7
             days prior to the start of study therapy or expected requirement for use of a strong
             or moderate inhibitor or inducer of CYP3A4 during study therapy.

         13. Concurrent participation in another therapeutic clinical trial.

         14. Any illness, medical condition, organ system dysfunction, or social situation,
             including mental illness or substance abuse, deemed by the Investigator to be likely
             to interfere with a subject's ability to sign informed consent, adversely affect the
             subject's ability to cooperate and participate in the study, or compromise the
             interpretation of study results.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Treatment-emergent adverse events (safety and tolerability)
Time Frame:Through study completion, on average 12 months
Safety Issue:
Description:via adverse event monitoring

Secondary Outcome Measures

Measure:antitumor activity and survival
Time Frame:From start of study therapy to the first documentation of disease progression or death from any cause, which ever came first, assessed up to 100 months
Safety Issue:
Description:determination of response and progression will be evaluated using RECIST 1.1

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Effector Therapeutics

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