Twice daily (except for single dose), 12 hours apart, fixed time is recommended

WJ05129:Twice daily (except for single dose), 12 hours apart, fixed time is recommended

WJ05129

Hongkai Wang

Yuan Wang

This study was an open, multicenter Phase I/II clinical study of WJ05129 in patients with locally advanced or metastatic malignant solid tumors in China, which was divided into three stages: dose escalation, dose extension and efficacy extension. The study included screening, treatment and follow-up periods. Dose escalation phase: adopt "3 + 3" dose escalation mode, preset 5 dose groups: 1.25mg, 2.5mg, 5mg, 7.5mg, 10mg, oral, twice a day (only once on the first day), planned to include a maximum of 30 subjects; Dose expansion phase: 2 dose groups will be planned in this phase, and the specific dose will be determined according to the trial data in the dose escalation phase. The maximum number of participants in each dose group will be 12. Efficacy expansion phase: It is preliminarily planned to expand three cohorts of Rb negative TNBC and SCLC and NB with high Myc expression, and recruit about 24 people in each cohort.

A Study of WJ05129 in Advanced Malignant Solid Tumors

A Phase I/II Clinical Study of WJ05129 Tablets in Patients With Locally Advanced or Metastatic Malignant Solid Tumors

It is suitable for dose escalation and dose extension.DLT is defined as any of the following toxic reactions that SMC considers to have occurred during the DLT observation period and may be causally related to WJ05129.

It is suitable for dose escalation and dose extension.Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in physical examination, ECOG score, vital signs, electrocardiogram, ophthalmic tests and laboratory tests.

It is suitable for dose escalation and dose extension.If the number of DLT patients is 0 and the next higher dose is unacceptable, the current dose is declared MTD.

It is suitable for dose escalation and dose extension.RP2D will be determined based on a combination of safety, tolerability, PK and/or pharmacodynamic studies .

It is suitable for the curative effect development stage.Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in physical examination, ECOG score, vital signs, electrocardiogram, ophthalmic tests and laboratory tests.

It is suitable for the curative effect development stage.Objective Response Rate by RECIST 1.1,IMWG,RANO,IWG and Lugano 2014.

It is suitable for dose escalation and dose extension.Maximum Plasma Concentration

It is suitable for dose escalation and dose extension.Time to Cmax

It is suitable for dose escalation and dose extension.Area under the concentration versus time curve from time 0 to the last measurable concentration

It is suitable for dose escalation and dose extension.AUC from time 0 to infinity

It is suitable for dose escalation and dose extension.Elimination half life time

It is suitable for dose escalation and dose extension.Clearance

It is suitable for dose escalation and dose extension.Apparent volume of distribution

It is suitable for dose escalation and dose extension.elimination rate constant

It is suitable for dose escalation and dose extension.Objective Response Rate by RECIST 1.1,IMWG,RANO,IWG and Lugano 2014.

It is suitable for the curative effect development stage

Sponsor GmbH

Suzhou Junjing BioSciences Co., Ltd.

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Lung Neoplasms

Esophageal Neoplasms

Triple Negative Breast Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Pembrolizumab

Mitogens

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

HR+/HER2- = Hormone receptor-positive/ human epidermal growth factor receptor 2-negative

Participants will receive enfortumab vedotin as an intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle.

Participants enrolled into Cohort 6 will be reallocated based on disease type and histology into Cohorts 7 or 8.

GEJ= gastroesophageal junction

Participants will receive enfortumab vedotin as an IV infusion on days 1 and 8 of each 21-day cycle. Pembrolizumab will be administered as an IV infusion on day 1 of each 21-day cycle.

enfortumab vedotin

pembrolizumab

Astellas Pharma Global Development, Inc.

Medical Director

The primary purpose of this study is to determine the antitumor activity of enfortumab vedotin as measured by confirmed objective response rate (ORR) per RECIST v1.1.

This study will also assess other measures of antitumor activity; overall survival (OS); as well as the safety and tolerability of enfortumab vedotin for cohorts 1 to 8 and enfortumab vedotin + pembrolizumab in cohort 9.

This study will consist of 3 periods: screening/baseline, treatment and follow-up.

Screening/baseline period will take place up to 28 days prior to the first dose of study treatment.

In the treatment period, starting at cycle 1, participants in cohorts 1 to 8 will receive enfortumab vedotin on days 1, 8, and 15 every 28-day cycle until one of the treatment discontinuation criteria are met. participants in cohort 9 will receive enfortumab vedotin on days 1, 8, and pembrolizumab on day 1 of every 21-day cycle until one of the treatment discontinuation criteria are met. Disease assessment will be performed at screening/baseline and repeated every 8 weeks (56 days ± 7 days) for cohorts 1 to 8 and first assessment at week 9 and thereafter every 6 weeks (42 days ± 7 days) for cohort 9 from the first dose of study treatment throughout the study until the participant has radiologically confirmed disease progression, initiates a new subsequent anticancer therapy, dies, withdraws consent, is lost to follow-up or the study closes, whichever occurs first.

Participants who discontinue study treatment for reasons other than radiologically-confirmed disease progression by RECIST Version 1.1 will enter into a post treatment follow-up period and continue to receive imaging scans every 8 weeks (56 days ± 7 days) for cohorts 1 to 8 and for cohort 9 first scan will be performed at 9 week and thereafter every 6 weeks (42 days ± 7 days) until the subject has radiologically confirmed disease progression (for cohort 9 confirmed progressive disease \[iCPD\] per modified RECIST 1.1 for immune-based therapeutics \[iRECIST\]), initiates a new anticancer therapy, dies, withdraws consent, is lost to follow-up or the study closes, whichever occurs first.

After 1 year on study treatment, the frequency of disease assessment will be reduced to every 12 weeks (84 days ± 7 days) for cohorts 1 to 8.

After 18 months on study treatment, the frequency of disease assessment will be reduced to every 9 weeks (63 days ± 7 days) for cohort 9.

Participants in cohorts 1to 8 who discontinue study treatment for reasons other than radiologically-confirmed disease progression by RECIST Version 1.1 will enter into a post treatment follow-up period and continue to receive imaging scans every 8 weeks (56 days ± 7 days).

Participants in cohort 9 who discontinue study treatment for reasons other than radiologically confirmed disease progression per iRECIST will enter into a post treatment follow-up period and have physical exams, ECOG and disease assessments every 6 weeks (± 7 days) up to 18 months after first dose, then every 9 weeks (± 7 days) until the subject has radiologically confirmed disease progression per iRECIST.

After radiologically-confirmed disease progression or initiation of subsequent anticancer therapy, whichever occurs first, participants will be contacted every 12 weeks in the long-term follow-up period for survival status until death, withdrawal of consent, lost to follow-up or study closure, whichever occurs first.

A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)

An Open-label, Multicenter, Multicohort, Phase 2 Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

Confirmed ORR is defined as the proportion of participants whose objective response is a confirmed CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 per investigator assessment.

Confirmed ORR is defined as the proportion of participants whose objective response is a confirmed CR or PR according to RECIST Version 1.1 per investigator assessment.

DOR is defined as the time from the date of first documented response (CR or PR that is subsequently confirmed) to the date of first documented progressive disease (PD) per RECIST version 1.1 or death due to any cause, whichever occurs first. DOR will only be calculated for participants achieving a confirmed CR or PR.

DCR is defined as the proportion of participants whose Best Overall Response (BOR) is confirmed CR or PR or stable disease (SD).

PFS is defined as the time from start of study treatment to first documentation of PD per RECIST version 1.1 or death due to any cause, whichever comes first.

OS is defined as the time from start of study treatment to date of death due to any cause.

AEs will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant administered enfortumab vedotin, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of enfortumab vedotin whether or not considered related to the enfortumab vedotin. An AE is considered "serious" if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); or other medically important events.

Number of participants with potentially clinically significant laboratory values.

Number of participants with potentially clinically significant vital sign values.

Number of participants with potentially clinically significant ECG values.

The ECOG scale will be used to assess performance status. Grades range from 0 (equals fully active, able to carry on all pre-disease performance without restriction), and 5 (equals dead).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of WJ05129 in Advanced Malignant Solid Tumors	NCT05326035	Locally Advance...	WJ05129	18 Years - 75 Years	Suzhou Junjing BioSciences Co., Ltd.
A Study to Evaluate Enfortumab Vedotin in Subjects With Locally Advanced or Metastatic Malignant Solid Tumors (EV-202)	NCT04225117	Locally Advance...	enfortumab vedo... pembrolizumab	18 Years -	Astellas Pharma Inc
A Study of WJ05129 in Advanced Malignant Solid Tumors	NCT05326035	Locally Advance...	WJ05129	18 Years - 75 Years	Suzhou Junjing BioSciences Co., Ltd.

Spots Global Cancer Trial Database for locally advanced or metastatic malignant solid tumors