Clinical Trials /

Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101

NCT04144140

Description:

This is an open label, multicenter, phase 1/1b study to assess safety/tolerability and preliminary clinical activity of E7766 as a single agent administered intratumorally in participants with advanced solid tumors or lymphomas.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101
  • Official Title: An Open-Label, Multicenter Phase 1/1b Study of Intratumorally Administered STING Agonist E7766 in Subjects With Advanced Solid Tumors or Lymphomas - INSTAL-101

Clinical Trial IDs

  • ORG STUDY ID: E7766-G000-101
  • SECONDARY ID: 2019-000160-17
  • NCT ID: NCT04144140

Conditions

  • Lymphoma
  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
E7766Dose Escalation: Advanced Solid Tumors or Lymphomas

Purpose

This is an open label, multicenter, phase 1/1b study to assess safety/tolerability and preliminary clinical activity of E7766 as a single agent administered intratumorally in participants with advanced solid tumors or lymphomas.

Detailed Description

      The Phase 1/1b study consist of two parts: Dose Escalation and Dose Expansion. In the Dose
      Escalation Part, E7766 will be administered intratumorally in participants with advanced
      solid tumors or lymphomas to assess safety/tolerability profile of E7766 and to determine the
      maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of E7766. In the Dose
      Expansion Part, E7766 at RP2D will be administered to participants with melanoma, head and
      neck squamous cell carcinoma (HNSCC), breast cancer, colorectal cancer, and/or other tumors
      including lymphomas to confirm safety and assess preliminary clinical activity of E7766 as a
      single agent. Clinical activity will be evaluated by objective response rate (ORR), duration
      of response (DOR), and disease control rate (DCR) on treatment with E7766.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation: Advanced Solid Tumors or LymphomasExperimental
  • E7766
Dose Expansion: Advanced Solid Tumors or LymphomasExperimentalDose identified from dose escalation part for E7766 will be used in dose expansion part.
  • E7766

Eligibility Criteria

        1. Participants with solid tumors or lymphomas, confirmed by available histopathology
             records or current biopsy, that are advanced, nonresectable, or recurrent and
             progressing since last antitumor therapy, and for which no alternative standard
             therapy exists.

          2. Participants must have a minimum of one injectable lesion which is also accessible for
             biopsy, and if available, one other measurable lesion also accessible for biopsy.

             An injectable lesion is defined as being measureable (defined below) with a maximum of
             3.0 centimeter (cm) longest diameter, accessible for injection as judged by the
             investigator, and has not been subjected to any prior intratumoral treatment or
             radiotherapy. Lesions selected for injection must not be too close to a major vessel
             and not be associated with increased risk of bleeding, example, subcapsular liver
             lesions or hypervascular tumors.

             Measurable lesions are:

               1. Solid tumors: At least 1 lesion of greater than or equal to (>=1) cm by longest
                  axial diameter or >=1.5 cm short axis diameter if a nodal lesion, which is
                  serially measurable according to modified Response evaluation criteria in solid
                  tumors (RECIST) 1.1 using CT/MRI or photography. Lesions that have had external
                  beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation
                  must show evidence of progression to be deemed a target lesion.

               2. Lymphoma: At least 1 lymph node with a longest diameter greater than (>)1.5 cm or
                  an extranodal lesion with a longest diameter >1.0 cm

          3. Participants with prior Hepatitis B or C are eligible if they have adequate liver
             function

          4. Adequate bone marrow function:

               1. Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3) (>=1.0*10^3
                  per microliter [/mcL])

               2. Platelets >=75,000/mm^3 (>=75*10^ 9 per liter [/L])

               3. Hemoglobin >=9.0 grams per deciliter (g/dL)

          5. Adequate liver function defined by:

               1. Adequate blood coagulation function as evidenced by an International Normalized
                  Ratio (INR) less than or equal to (<=)1.5

               2. Total bilirubin <=1.5*upper limit of the normal range (ULN) except for
                  unconjugated hyperbilirubinemia or Gilbert's syndrome

               3. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate
                  aminotransferase (AST) <=3*ULN (in the case of liver metastasis <=5*ULN) unless
                  there are bone metastases. Participants with ALP values >3*ULN and known to have
                  bone metastases can be included.

        Exclusion Criteria:

          1. Other malignancy active within the previous 2 years except for basal or squamous cell
             skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast
             that has completed curative therapy.

          2. Known human immunodeficiency virus (HIV) infection.

          3. Major surgery within 4 weeks before the first dose of study drug.

          4. Brain metastases that are untreated or in the posterior fossa or involve the meninges.
             Participants with stable or progressing brain metastases (except in the posterior
             fossa or involving the meninges) previously treated with brain stereotactic
             radiotherapy (SRT), whole-brain radiotherapy (WBRT) and/or surgery are allowed as long
             as the participant is asymptomatic neurologically and does not require immediate local
             intervention (radiotherapy and/or surgery). In addition, participants must be off
             immunosuppressive doses of systemic steroids (>10 milligram per day (mg/d) prednisone
             or equivalent) for at least 4 weeks before study drug administration.

          5. Prolongation of corrected QT (QTc) interval to >450 millisecond (msec) for males and
             females when electrolytes balance is normal.

          6. Females who are breastfeeding or pregnant at screening or baseline (as documented by a
             positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin
             [hCG]) test with a minimum sensitivity of 25 units per liter (IU/L) or equivalent
             units of ß-hCG [or hCG]). A separate baseline assessment is required if a negative
             screening pregnancy test was obtained more than 72 hours before the first dose of
             study drug.

          7. Females of childbearing potential must not have had unprotected sexual intercourse
             within 30 days before study entry and must agree to use a highly effective method of
             contraception (total abstinence [if it is their preferred and usual lifestyle], a
             contraceptive implant, an oral contraceptive, or have a vasectomized partner with
             confirmed azoospermia) throughout the entire study period and for 180 days after study
             drug discontinuation. For sites outside of the European Union, it is permissible that
             if a highly effective method of contraception is not appropriate or acceptable to the
             participant, then the participant must agree to use a medically acceptable method of
             contraception, that is, double barrier methods of contraception such as condom plus
             diaphragm or cervical/vault cap with spermicide. If currently abstinent, the
             participant must agree to use a highly effective method as described above if she
             becomes sexually active during the study period or for 180 days after study drug
             discontinuation. Females who are using hormonal contraceptives must have been on a
             stable dose of the same hormonal contraceptive product for at least 28 days before
             dosing and must continue to use the same contraceptive during the study and for 180
             days after study drug discontinuation.

          8. Male participants who are partners of women of childbearing potential must use a
             condom and spermicide and their female partners if of childbearing potential must use
             a highly effective method of contraception beginning at least 1 menstrual cycle prior
             to starting study drug(s), throughout the entire study period, and for 180 days after
             the last dose of study drug, unless the male participants are totally sexually
             abstinent or have undergone a successful vasectomy with confirmed azoospermia or
             unless the female partners have been sterilized surgically or are otherwise proven
             sterile. No sperm donation is allowed during the study period or for 180 days after
             study drug discontinuation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame:Cycle 1 (Cycle length is equal to [=] 21 days)
Safety Issue:
Description:DLTs are any of the toxicities occurring during the Cycle 1 and assessed by the investigator as related to study drug. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v.5.0).

Secondary Outcome Measures

Measure:Dose Escalation Part: Percentage of Participants With Objective Response
Time Frame:From date of first dose of study drug until first documentation of CR or PR (up to approximately 3 years 1 month)]
Safety Issue:
Description:
Measure:Dose Escalation Part: DOR
Time Frame:From first documented CR or PR until first documentation of recurrent or progressive disease or death (up to approximately 3 years 1 month)
Safety Issue:
Description:
Measure:Dose Escalation Part: Percentage of Participants With Disease Control
Time Frame:From first dose of study drug until until first documentation of CR or PR or SD (up to approximately 3 years 1 month)
Safety Issue:
Description:
Measure:Cmax: Maximum Observed Plasma Concentration for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:AUC: Area Under the Plasma Concentration Versus Time Curve for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:t1/2: Terminal Elimination Half-life for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:CL/F: Apparent Total Body Clearance for E7386
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:Vd/F: Apparent Volume of Distribution for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:CLr: Renal Clearance for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:R: Accumulation Ratio for E7766
Time Frame:Dose Escalation:Cycle 1 Day 1: 0-24 hours;Cycle 1 Day 8: 0-2 hours;Cycle 1 Day 15: 0-24 hours; Cycle 2 Day 1 through Cycle 6 Day 1:0-2 hours;Dose Expansion:Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 15: 0-2 hours; Cycle 2 Day 1:0-2 hours(Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:Dose Escalation Part: Fraction Excreted (fe) in Urine for E7766
Time Frame:Cycle 1 Day 1: 0-24 hours post dose;Cycle 1 Day 15: 0-24 hours post dose; (Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:Dose Escalation Part: Fraction Excreted (fe) in Feces for E7766
Time Frame:Cycle 1 Day 1: 0-24 hours post dose (Cycle length=21 days)
Safety Issue:
Description:In time frame ''0" hour signifies predose.
Measure:Dose Escalation and Dose Expansion: Progression Free Survival (PFS)
Time Frame:From first dose of study drug until confirmed PD or death (up to approximately 3 years 1 month)
Safety Issue:
Description:
Measure:Dose Escalation and Dose Expansion: Overall Survival (OS)
Time Frame:From first dose of study drug until death (up to approximately 3 years 1 month)
Safety Issue:
Description:
Measure:Dose escalation and Dose Expansion: Change in Tumor Size in Injected lesions and in Distant Non-injected Lesions
Time Frame:Solid Tumor: Cycle 1 (C1) Day 1 (D1) pre-dose, every 6 weeks pre-dose from C1D1 up to approximately 3 years 1 month; Lymphoma: C1D1 pre-dose, Week 9 pre-dose, every 12 weeks pre-dose from CIDI up to approximately 3 years 1 month (Cycle length=21 days)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eisai Inc.

Trial Keywords

  • Advanced Solid Tumors
  • E7766
  • Intratumoral Injection
  • Stimulator of Interferon Genes Agonist
  • Interferons
  • Antineoplastic Agents
  • Lymphoma
  • Melanoma
  • Head and Neck Squamous Cell Carcinoma
  • Breast Cancer
  • Colorectal Cancer

Last Updated

April 20, 2020