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

NCT ID: NCT04144140

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-24
• Study Completion Date: 2022-07-26

Brief Summary

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.

Conditions

Lymphoma; Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation: Advanced Solid Tumors or Lymphomas

Group Type: EXPERIMENTAL

E7766

Intervention Type: DRUG

E7766, solution, intratumorally

Dose Expansion: Advanced Solid Tumors or Lymphomas

Dose identified from dose escalation part for E7766 will be used in dose expansion part.

Group Type: EXPERIMENTAL

E7766

Intervention Type: DRUG

E7766, solution, intratumorally

Interventions

E7766

E7766, solution, intratumorally

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

H3 Biomedicine Inc.

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Yale New Haven Hospital

New Haven, Connecticut, United States

University of Miami Hospital Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Pittsburgh Medical Center and Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Institut Gustave Roussy

Villejuif, , France

Samsung Medical Center

Seoul, , South Korea

Hospital Universitario Vall d'Hebrón

Barcelona, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

START Madrid

Madrid, , Spain

INCLIVA Hospital Clínico Universitario de Valencia

Valencia, , Spain

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

United States; France; South Korea; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-000160-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E7766-G000-101

Identifier Type: -

Identifier Source: org_study_id