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Non-Muscle Invasive Bladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Pharmaceutical Solutions

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Interferons

BCG Vaccine

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 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

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

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).

H3 Biomedicine Inc.

Eisai Inc.

Mitomycins

Mitomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Participants will receive 40 milligrams (mg) MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 20,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 60,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 200,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 400,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Participants will receive 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 800,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Mitomycin C

Chemophase

The purpose of this study is to explore a treatment that potentially enhances the delivery of chemotherapy to tumors in participants with superficial bladder cancer. The investigational medication to be studied is an enzyme called ChemophaseTM (recombinant human hyaluronidase, rHuPH20). Chemophase is being specifically developed for use with other anticancer drug to increase the local penetration of the anticancer drug for the treatment of superficial bladder cancer. In this study, Chemophase will be given in combination with mitomycin C directly into the bladder. Mitomycin C is an anti-tumor drug that is commonly used to treat superficial bladder cancer. It is envisioned that Chemophase with mitomycin C may potentially increase the local penetration of mitomycin C into remaining cancer cells following surgery to treat superficial bladder cancer.

The primary objectives of this study are to:

1. determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of escalating doses of Chemophase in combination with mitomycin (mitomycin C, MMC) administered as weekly intravesical instillations for five weeks, and
2. establish the dose of Chemophase with MMC recommended for future studies.

The secondary objectives of this study are to:

1. assess the pharmacokinetics of intravesical administration of MMC alone and in combination with intravesical administration of Chemophase,
2. for those participants treated at the MTD, assess the safety and tolerability of intravesical administration of MMC with Chemophase over up to 7 additional maintenance treatments every 3 months following the initial six weekly instillations, and
3. observe participants for any preliminary evidence of anti-tumor activity of MMC and Chemophase when combined.

Study participants will receive six weekly study treatments administered intravesically (at Weeks 1 through 6) followed by post-treatment evaluations, at Weeks 8 and 12. The 12 participants treated at MTD will continue to receive combination therapy every three months until the end of Year 2 or until the time of documented tumor recurrence, whichever occurs first. For other participants, long-term follow-up after Week 12 will consist of disease monitoring of participants by telephone and will be performed every three months beginning three months after last study treatment for two years and then every six months thereafter, until bladder tumor recurrence.

Safety Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Participants With Superficial Bladder Cancer

A Phase 1-2a, Multicenter, Open-Label, Multiple Dose, Safety, Tolerability, and Pharmacokinetic Study of Recombinant Human Hyaluronidase (Chemophase®) in Combination With Mitomycin in Patients With Non-Muscular-Invasive Bladder Cancer

The MTD was defined as the maximum dose level at which no more than two of six participants experienced dose-limiting toxicities (DLT). DLT was defined as any of the following:

* Plasma MMC concentration greater than or equal to (\>=) 100 nanograms (ng)/milliliter (mL)
* Adverse event (AE) with a Common Toxicity Criteria (CTC) grade greater than or equal to 3
* New, treatment-emergent diagnosis of bladder fibrosis.

DLT was defined as any of the following:

* Plasma MMC concentration \>= 100 ng/mL
* AE with a CTC grade greater than or equal to 3
* New, treatment-emergent diagnosis of bladder fibrosis.

A quantifiable MMC plasma concentration value was a value that was not below the quantifiable limit (BQL) of \<10.0 nanogram/milliliter (ng/mL).

TEAEs were defined as any AE that occurred after the first administration of the study drug and until the end of the study. AEs were defined as any untoward medical occurrence in a participant administered study drug and that did not necessarily have a causal relationship with the study drug. SAEs were defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.

Halozyme Therapeutics

The Safety Set included all participants who received one or more doses of Chemophase.

Participants received 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 20,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Cohort 1: MMC Plus Chemophase 20,000 U

Participants received 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 60,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Cohort 2: MMC Plus Chemophase 60,000 U

Participants received 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 200,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Cohort 3: MMC Plus Chemophase 200,000 U

Participants received 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 400,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Cohort 4: MMC Plus Chemophase 400,000 U

Participants received 40 mg MMC intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 800,000 U Chemophase intravesically once weekly from Weeks 2 through 6.

Cohort 5: MMC Plus Chemophase 800,000 U

Total

Age, Continuous

Sex: Female, Male

Chief Medical Officer

The Intent-To-Treat (ITT) Set included all participants who received one or more doses of Chemophase with MMC.

Maximum Tolerated Dose (MTD) of Chemophase in Combination With MMC

ITT Set included all participants who received one or more doses of Chemophase with MMC.

Number of Participants With Dose Limiting Toxicities (DLTs)

Recommended Dose of Chemophase With MMC For Future Studies

Week 1: Predose

Week 1: 1 hour

Week 1: 2 hours

Week 1: 3 hours

Week 2: Predose

Week 2: 1 hour

Week 2: 2 hours

Week 2: 3 hours

Week 5: Predose

Week 5: 1 hour

Week 5: 2 hours

Week 5: 3 hours

Week 6: Predose

Week 6: 1 hour

Week 6: 2 hours

Week 6: 3 hours

Number of Participants With a Quantifiable MMC Plasma Concentration Value

TEAEs

SAEs

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of Participants Who Remained Tumor Free at the End of the Study

Participants received 40 milligrams (mg) mitomycin C (MMC) intravesically on Day 1 of Week 1 followed by a combination of 40 mg MMC and 20,000 Units (U) Chemophase intravesically once weekly from Weeks 2 through 6.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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.
Safety Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Participants With Superficial Bladder Cancer	NCT00318643	Bladder Cancer	Mitomycin C Chemophase	18 Years -	Halozyme Therapeutics
Safety Study of Recombinant Human Hyaluronidase (Chemophase) in Combination With Mitomycin in Participants With Superficial Bladder Cancer	NCT00318643	Bladder Cancer	Mitomycin C Chemophase	18 Years -	Halozyme Therapeutics
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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