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

E7766

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.

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

An Open-Label, Multicenter Phase 1/1b Study of Intratumorally Administered STING Agonist E7766 in Subjects With Advanced Solid Tumors or Lymphomas - INSTAL-101

Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cmax was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.

Tmax was quantified using validated liquid LC-MS/MS methods.

AUC was quantified using validated liquid LC-MS/MS methods.

AUC(0-inf) was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods.

t1/2 was quantified using validated liquid LC-MS/MS methods.

CL/F was quantified using validated liquid LC-MS/MS methods.

Vd/F was quantified using validated liquid LC-MS/MS methods.

CLr was quantified using validated liquid LC-MS/MS methods.

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.

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.

fe was defined as fraction of administered drug (E7766) excreted/recovered in urine. fe was quantified using validated liquid LC-MS/MS methods.

fe was defined as fraction of administered drug (E7766) excreted/recovered in feces. fe was quantified using validated liquid LC-MS/MS methods.

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).

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.

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.

Percent change from baseline in tumor size was calculated for the first injected lesion based on Investigator Assessment.

H3 Biomedicine Inc.

Eisai Inc.

The safety data was collected for Dose Escalation Part of the study only as no participants were enrolled in the Dose Expansion part of E7766. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Participants received E7766 75 mcg, injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until PD or until other discontinuation criteria whichever occurred first.

Dose Escalation Part: E7766 75 mcg

Participants received E7766 150 mcg injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until PD or until other discontinuation criteria whichever occurred first.

Dose Escalation Part: E7766 150 mcg

Participants received E7766 300 mcg injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until PD or until other discontinuation criteria whichever occurred first.

Dose Escalation Part: E7766 300 mcg

Participants received E7766 600 mcg injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until PD or until other discontinuation criteria whichever occurred first.

Dose Escalation Part: E7766 600 mcg

Participants received E7766 780 mcg injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until PD or until other discontinuation criteria whichever occurred first.

Dose Escalation Part: E7766 780 mcg

Participants received E7766 1000 mcg injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until PD or until other discontinuation criteria whichever occurred first.

Dose Escalation Part: E7766 1000 mcg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The full analysis set included all participants who received at least 1 dose of study drug. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

The study was terminated earlier due to corporate strategic decision, which is unrelated to safety. In addition, there is no clinical activity data that informed the decision. Therefore, no participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Eisai Medical Information

The DLT analysis set included all participants in the Dose Escalation part who completed Cycle 1 without incurring certain major protocol deviations (for instance those related to dosing or others identified before database lock) with at least 2 E7766 injections during Cycle 1 and were evaluable for DLT, or participants who experienced DLT during Cycle 1.

Dose Escalation Part: Number of Participants With Dose-limiting Toxicities (DLTs)

Participants were planned to receive the dose identified from dose escalation part for E7766 in dose expansion part. Since no participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Dose Expansion Part

The safety analysis set included all participants who received at least 1 dose of study drug. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part.

Number of Participants With Any Treatment-emergent Adverse Events (TEAEs)

The full analysis set included all participants who received at least 1 dose of study drug. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part.

Dose Expansion Part: Objective Response Rate Based on Modified Response Evaluation Criteria In Solid Tumors (mRECIST) v1.1

Dose Expansion Part: ORR Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)

Dose Expansion Part: Duration of Response (DOR) Based on mRECIST v1.1

Dose Expansion Part: DOR Based on iRECIST

Dose Expansion Part: Disease Control Rate (DCR) Based on mRECIST v1.1

Participants were planned to receive the dose identified from dose escalation part for E7766 in dose expansion part. Since no participants were enrolled in the Dose Expansion part of E7766. Hence, no data collection and analysis were done during Dose Expansion part of this study.

Dose Expansion Part: DCR Based on iRECIST

The full analysis set included all participants who received at least 1 dose of study drug.

Dose Escalation Part: ORR Based on iRECIST

Dose Escalation Part: ORR Based on mRECIST v1.1

The full analysis set included all participants who received at least 1 dose of study drug. Here, Overall number of participants analyzed signifies participants who had overall response (OR) (CR or PR) as per Investigator Assessment.

Dose Escalation Part: DOR Based on iRECIST

The full analysis set included all participants who received at least 1 dose of study drug. Here, Overall number of participants analyzed signifies participants who had OR (CR or PR) as per Investigator Assessment.

Dose Escalation Part: DOR Based on mRECIST v1.1

Dose Escalation Part: DCR Based on iRECIST

Dose Escalation Part: DCR Based on mRECIST v1.1

Cycle 1 Day 1

Cycle 1 Day 15

Dose identified from dose escalation part for E7766 was planned be used in dose expansion part. Since no participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part of this study.

The Pharmacokinetic (PK) analysis set included the group of participants who have received at least 1 dose of study drug and have at least 1 evaluable plasma concentration. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part. Here number analyzed "n" are the participants who were evaluable for this outcome measure for given timepoints.

Cmax: Maximum Observed Plasma Concentration for E7766

The PK analysis set included the group of participants who have received at least 1 dose of study drug and have at least 1 evaluable plasma concentration. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part.Here number analyzed "n" are the participants who were evaluable for this outcome measure for given timepoints.

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7766

The PK analysis set included the group of participants who have received at least 1 dose of study drug and have at least 1 evaluable plasma concentration. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part. Here number analyzed "n" are the participants who were evaluable for this outcome measure for given timepoints.

Part: AUC(0-t): Area Under the Plasma Concentration From Time Zero to Last Curve for E7766

The PK analysis set included the group of participants who have received at least 1 dose of study drug and have at least 1 evaluable plasma concentration. No participants were enrolled in the Dose Expansion part. Hence, no data collection and analysis were done during Dose Expansion part. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for given timepoints.

AUC(0-inf): Area Under the Plasma Concentration From Time Zero to Infinity Curve for E7766

t1/2: Terminal Elimination Half-life for E7766

The PK analysis set included the group of participants who have received at least 1 dose of study drug and have at least 1 evaluable plasma concentration. As planned, this outcome measure was assessed in dose escalation part only. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure and number analyzed "n" are the participants who were evaluable for given timepoints.

Dose Escalation Part: CL/F: Apparent Total Body Clearance for E7766

Dose Escalation Part: Vd/F: Apparent Volume of Distribution for E7766

Dose Escalation Part: CLr: Renal Clearance for E7766

The PK analysis set included the group of participants who have received at least 1 dose of study drug and have at least 1 evaluable plasma concentration. As planned, this outcome measure was assessed in dose escalation part only. Here overall number analyzed "N" were the participants who were evaluable for the outcome measure.

Dose Escalation Part: Rac (Cmax): Accumulation Ratio Based on Cmax for E7766

Dose Escalation Part: Rac (AUC0-t): Accumulation Ratio Based on AUC for E7766

Dose Escalation Part: Percentage (Fraction) Excreted (fe) in Urine for E7766

Dose Escalation Part: Percentage (Fraction) Excreted (fe) in Feces for E7766

Progression Free Survival (PFS) Based on mRECIST v1.1

PFS Based on iRECIST

Overall Survival (OS)

Percent Change From Baseline in Tumor Size

Participants received E7766 75 microgram (mcg), injection, intratumorally on Days 1, 8, and 15 in the first cycle of 21 days and then on Day 1 of each subsequent 21-days cycle, once every 3 weeks until progressive disease (PD) or until other discontinuation criteria whichever occurred first.

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Carcinoma in Situ

Non-Muscle Invasive Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

BCG Vaccine

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 intravesically in participants with NMIBC. Both intermediate risk and BCG-unresponsive NMIBC participants will be included.

The Phase 1/1b study consist of two parts: Dose Escalation and Dose Expansion. In the Dose Escalation Part, E7766 will be administered intravesically to participants with intermediate risk NMIBC or participants with BCG unresponsive NMIBC with increased dose levels 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 NMIBC with or without carcinoma in situ (CIS) to confirm safety and assess preliminary clinical activity of E7766 as a single agent. Clinical activity will be evaluated by complete response (CR) rates at 3 months, 6 months, 12 months, 18 months, 24 months, and by duration of complete response (DOCR) in all participants who have achieved CR on treatment with E7766.

A Study of Stimulator of Interferon Genes (STING) Agonist E7766 in Non-muscle Invasive Bladder Cancer (NMIBC) Including Participants Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy, INPUT-102

INtravesical Phase 1/1b Study of STING Agonist E7766 in NMIBC Including Subjects Unresponsive to BCG Therapy, INPUT-102

DLTs are any of the toxicities occurring during the 6 weeks of the Induction Cycle 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).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101	NCT04144140	Lymphoma Advanced Solid ...	E7766	18 Years -	Eisai Inc.
A Study of Stimulator of Interferon Genes (STING) Agonist E7766 in Non-muscle Invasive Bladder Cancer (NMIBC) Including Participants Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy, INPUT-102	NCT04109092	Urinary Bladder...	E7766	18 Years -	Eisai Inc.
Study of Intratumorally Administered Stimulator of Interferon Genes (STING) Agonist E7766 in Participants With Advanced Solid Tumors or Lymphomas - INSTAL-101	NCT04144140	Lymphoma Advanced Solid ...	E7766	18 Years -	Eisai Inc.
A Study of Stimulator of Interferon Genes (STING) Agonist E7766 in Non-muscle Invasive Bladder Cancer (NMIBC) Including Participants Unresponsive to Bacillus Calmette-Guerin (BCG) Therapy, INPUT-102	NCT04109092	Urinary Bladder...	E7766	18 Years -	Eisai Inc.

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