LymphomaPhase 1NCT04144140
Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101
A Phase 1 study testing E7766 in people with Lymphoma and Advanced Solid Tumors, run by Eisai Inc. at 13 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma, Advanced Solid Tumors
- What is being tested?
- E7766
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 24 Feb 2020to 26 Jul 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
- Known human immunodeficiency virus (HIV) infection.
- Major surgery within 4 weeks before the first dose of study drug.
- 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.
- Prolongation of corrected QT (QTc) interval to >450 millisecond (msec) for males and females when electrolytes balance is normal.
- 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.
- 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.
- 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.
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
United States6 sites
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Miami Hospital Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Yale New Haven Hospital
New Haven, Connecticut, 06510
University of Pittsburgh Medical Center and Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Spain4 sites
Hospital Universitario Vall d'Hebrón
Barcelona, 08035
Hospital Universitario 12 de Octubre
Madrid, 28041
START Madrid
Madrid, 28050
INCLIVA Hospital Clínico Universitario de Valencia
Valencia, 46010
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0HS
About this study
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
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.
Read the 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
- Being tested
- E7766
- Keywords
- Advanced Solid Tumors, E7766, Intratumoral Injection, Stimulator of Interferon Genes Agonist, Interferons, Antineoplastic Agents, Lymphoma, Melanoma, Breast Cancer, Colorectal Cancer, Squamous Cell Carcinoma of the Head and Neck, Oesophageal Squamous Cell Carcinoma, Adenocarcinoma of the Gastroesophageal Junction or Gastric
- Medical subject headings
- Lymphoma, Melanoma, Breast Neoplasms, Colorectal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
E7766Drug
E7766, solution, intratumorally
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: Advanced Solid Tumors or Lymphomas | Experimental | Not described Receives: Drug: E7766 |
| Dose Expansion: Advanced Solid Tumors or Lymphomas | Experimental | Dose identified from dose escalation part for E7766 will be used in dose expansion part. Receives: Drug: E7766 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation Part: Number of Participants With Dose-limiting Toxicities (DLTs)
DLTs were predefined as any of the following toxicities occurring during Cycle 1 and were assessed by the investigator according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version (v) 5.0. as related to E7766. Nonhematologic toxicity greater than or equal to (>=) Grade 3 (NCI CTCAE v. 5.0), except Grade 3 fatigue less than (<) 5 days. Asymptomatic Grade 3 or 4 laboratory abnormalities that were corrected within 72 hours. >=Grade 3 nausea, vomiting, and diarrhea unless lasting greater than (>) 48 hours despite optimal supportive care. Hematologic toxicity: Grade 4 neutropenia for >=5 days, or febrile neutropenia. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with hemorrhage. A DLT may have continued treatment at a reduced dose if the DLT had resolved and in the opinion of the investigator the participant was benefiting from treatment. In case of recurrence of the DLT at a lower dose, E7766 treatment was discontinued.
Measured: Cycle 1 (Cycle length= 21 days)
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as an adverse event (AE) that emerges during treatment (on or after the first dose of study drug up to 90 days after the participant's last dose) or start day of another anticancer therapy, whichever is earlier; or in case participant has initiated new anticancer therapy within 30 days, then AEs occurring for 30 days following the last dose of E7766, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.
Measured: From the first dose of the study drug up to 90 days after the last dose (up to 9 months and 14 days)
Dose Expansion Part: Objective Response Rate Based on Modified Response Evaluation Criteria In Solid Tumors (mRECIST) v1.1
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 as per investigator assessment for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
Measured: From date of first dose of study drug until confirmed CR or PR (up to 29 months)
Dose Expansion Part: ORR Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
ORR was defined as the percentage of participants whose BOR was iCR or iPR according to iRECIST as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions iSD: immune stable disease in the absence of iCR or iPD. iUPD: immune unconfirmed progressive disease when iPD is unconfirmed NE: not evaluable.
Measured: From date of first dose of study drug until confirmed iCR or iPR (up to 29 months)
Dose Expansion Part: Duration of Response (DOR) Based on mRECIST v1.1
DOR was defined as time from the first documented of CR or PR to the date of first documentation of PD based on modified RECIST 1.1 as per investigator assessment or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
Measured: From first documented confirmed CR or PR until first documentation of PD or death (up to 29 months)
Dose Expansion Part: DOR Based on iRECIST
DOR: time from date of first observation of response (iPR or iCR) to date of the first observation of progression based on iRECIST 1.1 as per investigator assessment, or date of death, whatever the cause. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first documented confirmed iCR or iPR until first documentation of iPD or death (up to 29 months)
Dose Expansion Part: Disease Control Rate (DCR) Based on mRECIST v1.1
DCR was defined as the percentage of participants with a best overall response of CR or PR, or stable disease (SD) based on mRECIST 1.1 as per investigator assessment. Best overall response of SD must have been >=5 weeks after randomization. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or PD and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Measured: From first dose of study drug until confirmed CR or PR or >=5 weeks after first dose for SD (up to 29 months)
Dose Expansion Part: DCR Based on iRECIST
DCR: percentage of participants with a confirmed iCR, iPR, or i-SD (duration of iSD >=5 weeks). DCR was assessed on iRECIST v1.1 as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions iSD: immune stable disease in the absence of iCR or iPD. iUPD: immune unconfirmed progressive disease when iPD is unconfirmed NE: not evaluable.
Measured: From first dose of study drug until confirmed iCR or iPR or >=5 weeks after first dose for iSD (up to 29 months)
Secondary outcomes (22)
Dose Escalation Part: ORR Based on iRECIST
ORR was defined as the percentage of participants whose BOR was iCR or iPR according to iRECIST as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions iSD: immune stable disease in the absence of iCR or iPD iUPD: immune unconfirmed progressive disease when iPD is unconfirmed NE: not evaluable.
Measured: From date of first dose of study drug until confirmed iCR or iPR (up to 6 months and 18 days)
Dose Escalation Part: ORR Based on mRECIST v1.1
ORR was defined as the percentage of participants with a BOR of CR or PR for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 as per investigator assessment for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
Measured: From date of first dose of study drug until confirmed CR or PR (up to 6 months and 18 days)
Dose Escalation Part: DOR Based on iRECIST
DOR: time from date of first observation of response (iPR or iCR) to date of the first observation of progression based on iRECIST 1.1 as per investigator assessment, or date of death, whatever the cause. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first documented confirmed iCR or iPR until first documentation of iPD or death (up to 6 months and 18 days)
Dose Escalation Part: DOR Based on mRECIST v1.1
DOR was defined as time from the first documented of CR or PR to the date of first documentation of PD based on modified RECIST 1.1as per investigator assessment or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
Measured: From first documented confirmed CR or PR until first documentation of PD or death (up to 6 months and 18 days)
Dose Escalation Part: DCR Based on iRECIST
DCR: percentage of participants with a confirmed iCR, iPR, or i-SD (duration of iSD >=5 weeks). DCR was assessed on iRECIST v1.1 as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions iSD: immune stable disease in the absence of iCR or iPD iUPD: immune unconfirmed progressive disease when iPD is unconfirmed NE: not evaluable.
Measured: From first dose of study drug until confirmed iCR or iPR or >=5 weeks after first dose for iSD (up to 6 months and 18 days)
Dose Escalation Part: DCR Based on mRECIST v1.1
DCR was defined as the percentage of participants with a best overall response of CR or PR, or SD based on mRECIST 1.1 as per investigator assessment. Best overall response of SD must have been >=7 weeks after randomization. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or PD and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Measured: From first dose of study drug until confirmed CR or PR or >=5 weeks after first dose for SD (up to 6 months and 18 days)
Cmax: Maximum Observed Plasma Concentration for E7766
Cmax was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766
Tmax was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
Part: AUC(0-t): Area Under the Plasma Concentration From Time Zero to Last Curve for E7766
AUC was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
AUC(0-inf): Area Under the Plasma Concentration From Time Zero to Infinity Curve for E7766
AUC(0-inf) was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
t1/2: Terminal Elimination Half-life for E7766
t1/2 was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
Dose Escalation Part: CL/F: Apparent Total Body Clearance for E7766
CL/F was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Vd/F: Apparent Volume of Distribution for E7766
Vd/F was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: CLr: Renal Clearance for E7766
CLr was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Rac (Cmax): Accumulation Ratio Based on Cmax for E7766
Rac (Cmax) was calculated as the ratio of Cmax on Cycle 1 Day 15 divided by Cmax on Cycle 1 Day 1. Accumulation ratio was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Rac (AUC0-t): Accumulation Ratio Based on AUC for E7766
Rac (AUC0-t) was calculated as the ratio of AUC(0-t) on Cycle 1 Day 15 divided by AUC(0-t) on Cycle 1 Day 1. Accumulation ratio was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Percentage (Fraction) Excreted (fe) in Urine for E7766
fe was defined as fraction of administered drug (E7766) excreted/recovered in urine. fe was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Percentage (Fraction) Excreted (fe) in Feces for E7766
fe was defined as fraction of administered drug (E7766) excreted/recovered in feces. fe was quantified using validated liquid LC-MS/MS methods.
Measured: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Progression Free Survival (PFS) Based on mRECIST v1.1
PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on mRECIST v1.1 as per investigator assessment. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
Measured: From first dose of study drug until confirmed PD or death up to 6 months 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
PFS Based on iRECIST
PFS was defined as the time from the first dose date to the date of iPD or date of death (whichever occurred first) according to iRECIST version 1.1 as per investigator assessment. iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: From first dose of study drug until confirmed PD or death up to 6 months 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
Overall Survival (OS)
OS was measured from the date of first dose of study drug until date of death from any cause. OS event was defined as deaths no later than data cut off date or date of death of a participant.
Measured: From first dose of study drug until confirmed PD or death up to 6 months 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
Percent Change From Baseline in Tumor Size
Percent change from baseline in tumor size was calculated for the first injected lesion based on Investigator Assessment.
Measured: Baseline to up to 6 months and 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study start24 Feb 2020
- Primary completion26 Jul 2022
- Study completion26 Jul 2022
Why it stopped: The study was terminated earlier due to a business decision; which was unrelated to safety. In addition, there was no clinical activity data that informed the decision.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H3 Biomedicine Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04144140
- Sponsor's protocol ID
- E7766-G000-101
- Other IDs
- 2019-000160-17, 2019
- Status last verified
- Mar 2023
- First submitted
- 28 Oct 2019
- Last updated
- 7 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04144140
- Acronym / sponsor ID
- E7766-G000-101
- Conditions
- Lymphoma, Advanced Solid Tumors
- Keywords
- Advanced Solid Tumors, E7766, Intratumoral Injection, Stimulator of Interferon Genes Agonist, Interferons, Antineoplastic Agents, Lymphoma, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated earlier due to a business decision; which was unrelated to safety. In addition, there was no clinical activity data that informed the decision.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- H3 Biomedicine Inc.
- Study start
- 24 Feb 2020 (actual)
- Primary completion
- 26 Jul 2022 (actual)
- Study completion
- 26 Jul 2022 (actual)
- First posted
- 30 Oct 2019 (actual)
- Results
- Posted 7 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: Advanced Solid Tumors or Lymphomas | Experimental | Drug: E7766 |
| Dose Expansion: Advanced Solid Tumors or Lymphomas | Experimental | Drug: E7766Dose identified from dose escalation part for E7766 will be used in dose expansion part. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- 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.
- Known human immunodeficiency virus (HIV) infection.
- Major surgery within 4 weeks before the first dose of study drug.
- 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.
- Prolongation of corrected QT (QTc) interval to >450 millisecond (msec) for males and females when electrolytes balance is normal.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| E7766E7766, solution, intratumorally | Drug | Dose Escalation: Advanced Solid Tumors or Lymphomas, Dose Expansion: Advanced Solid Tumors or Lymphomas |
Primary outcome
Dose Escalation Part: Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: Cycle 1 (Cycle length= 21 days)
DLTs were predefined as any of the following toxicities occurring during Cycle 1 and were assessed by the investigator according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version (v) 5.0. as related to E7766. Nonhematologic toxicity greater than or equal to (>=) Grade 3 (NCI CTCAE v. 5.0), except Grade 3 fatigue less than (<) 5 days. Asymptomatic Grade 3 or 4 laboratory abnormalities that were corrected within 72 hours. >=Grade 3 nausea, vomiting, and diarrhea unless lasting greater than (>) 48 hours despite optimal supportive care. Hematologic toxicity: Grade 4 neutropenia for >=5 days, or febrile neutropenia. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with hemorrhage. A DLT may have continued treatment at a reduced dose if the DLT had resolved and in the opinion of the investigator the participant was benefiting from treatment. In case of recurrence of the DLT at a lower dose, E7766 treatment was discontinued.
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)
Time frame: From the first dose of the study drug up to 90 days after the last dose (up to 9 months and 14 days)
A TEAE was defined as an adverse event (AE) that emerges during treatment (on or after the first dose of study drug up to 90 days after the participant's last dose) or start day of another anticancer therapy, whichever is earlier; or in case participant has initiated new anticancer therapy within 30 days, then AEs occurring for 30 days following the last dose of E7766, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE is continuous.
Dose Expansion Part: Objective Response Rate Based on Modified Response Evaluation Criteria In Solid Tumors (mRECIST) v1.1
Time frame: From date of first dose of study drug until confirmed CR or PR (up to 29 months)
ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 as per investigator assessment for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
Dose Expansion Part: ORR Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Time frame: From date of first dose of study drug until confirmed iCR or iPR (up to 29 months)
ORR was defined as the percentage of participants whose BOR was iCR or iPR according to iRECIST as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions iSD: immune stable disease in the absence of iCR or iPD. iUPD: immune unconfirmed progressive disease when iPD is unconfirmed NE: not evaluable.
Dose Expansion Part: Duration of Response (DOR) Based on mRECIST v1.1
Time frame: From first documented confirmed CR or PR until first documentation of PD or death (up to 29 months)
DOR was defined as time from the first documented of CR or PR to the date of first documentation of PD based on modified RECIST 1.1 as per investigator assessment or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
Dose Expansion Part: DOR Based on iRECIST
Time frame: From first documented confirmed iCR or iPR until first documentation of iPD or death (up to 29 months)
DOR: time from date of first observation of response (iPR or iCR) to date of the first observation of progression based on iRECIST 1.1 as per investigator assessment, or date of death, whatever the cause. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Dose Expansion Part: Disease Control Rate (DCR) Based on mRECIST v1.1
Time frame: From first dose of study drug until confirmed CR or PR or >=5 weeks after first dose for SD (up to 29 months)
DCR was defined as the percentage of participants with a best overall response of CR or PR, or stable disease (SD) based on mRECIST 1.1 as per investigator assessment. Best overall response of SD must have been >=5 weeks after randomization. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference the baseline sum of the diameters of target lesions. SD was when a case does not qualify for either PR or PD and was new non-target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions.
Dose Expansion Part: DCR Based on iRECIST
Time frame: From first dose of study drug until confirmed iCR or iPR or >=5 weeks after first dose for iSD (up to 29 months)
DCR: percentage of participants with a confirmed iCR, iPR, or i-SD (duration of iSD >=5 weeks). DCR was assessed on iRECIST v1.1 as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions iSD: immune stable disease in the absence of iCR or iPD. iUPD: immune unconfirmed progressive disease when iPD is unconfirmed NE: not evaluable.
22 secondary outcomes
Dose Escalation Part: ORR Based on iRECIST
Time frame: From date of first dose of study drug until confirmed iCR or iPR (up to 6 months and 18 days)
Dose Escalation Part: ORR Based on mRECIST v1.1
Time frame: From date of first dose of study drug until confirmed CR or PR (up to 6 months and 18 days)
Dose Escalation Part: DOR Based on iRECIST
Time frame: From first documented confirmed iCR or iPR until first documentation of iPD or death (up to 6 months and 18 days)
Dose Escalation Part: DOR Based on mRECIST v1.1
Time frame: From first documented confirmed CR or PR until first documentation of PD or death (up to 6 months and 18 days)
Dose Escalation Part: DCR Based on iRECIST
Time frame: From first dose of study drug until confirmed iCR or iPR or >=5 weeks after first dose for iSD (up to 6 months and 18 days)
Dose Escalation Part: DCR Based on mRECIST v1.1
Time frame: From first dose of study drug until confirmed CR or PR or >=5 weeks after first dose for SD (up to 6 months and 18 days)
Cmax: Maximum Observed Plasma Concentration for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
Part: AUC(0-t): Area Under the Plasma Concentration From Time Zero to Last Curve for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
AUC(0-inf): Area Under the Plasma Concentration From Time Zero to Infinity Curve for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
t1/2: Terminal Elimination Half-life for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose; Dose Expansion: Cycle 1 Days 1 and 15: predose up to 2 hours postdose (Cycle length=21 days)
Dose Escalation Part: CL/F: Apparent Total Body Clearance for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Vd/F: Apparent Volume of Distribution for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: CLr: Renal Clearance for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Rac (Cmax): Accumulation Ratio Based on Cmax for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Rac (AUC0-t): Accumulation Ratio Based on AUC for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Percentage (Fraction) Excreted (fe) in Urine for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Dose Escalation Part: Percentage (Fraction) Excreted (fe) in Feces for E7766
Time frame: Dose Escalation: Cycle 1 Days 1 and 15: predose and up to 24 hours postdose (Cycle length=21 days)
Progression Free Survival (PFS) Based on mRECIST v1.1
Time frame: From first dose of study drug until confirmed PD or death up to 6 months 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
PFS Based on iRECIST
Time frame: From first dose of study drug until confirmed PD or death up to 6 months 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
Overall Survival (OS)
Time frame: From first dose of study drug until confirmed PD or death up to 6 months 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
Percent Change From Baseline in Tumor Size
Time frame: Baseline to up to 6 months and 18 days (Dose Escalation Part) and up to 29 months (Dose Expansion Part)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing E7766 in people with Lymphoma and Advanced Solid Tumors, run by Eisai Inc. at 13 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Spain, France, South Korea, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Escalation Part: Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (Cycle length= 21 days)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2024.