Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Carboplatin

Cisplatin

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Enfortumab vedotin + pembrolizumab + Cisplatin or carboplatin

Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle

Enfortumab vedotin

IV infusion on Day 1 of every 3-week cycle

administered as IV infusion on Day 1 of each 3-week cycle

Dosed according to local guidelines and will be administered as IV infusion on Day 1 of each 3-week cycle

IV infusion on Days 1 and 8 of every 3 week cycle

Seagen Inc. Trial Information Support

Zejing Wang, MD, PhD

John Lu, MD

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together to treat patients with urothelial cancer. The study will compare these drugs to other drugs that are usually used to treat this cancer (standard of care). The patients in this study will have cancer that has spread from their urinary system to other parts of their body.

Japan PMDA has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.

This study is being conducted to evaluate the combination of enfortumab vedotin + pembrolizumab versus standard of care gemcitabine + platinum-containing chemotherapy, in subjects with previously untreated locally advanced or metastatic urothelial cancer.

Enfortumab vedotin may be administered for an unlimited number of cycles until a protocol defined reason for study discontinuation occurs. Pembrolizumab may be administered for a maximum of 35 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first. Cisplatin or carboplatin plus gemcitabine may be administered for a maximum of 6 cycles or a protocol-defined reason for study discontinuation occurs, whichever is first.

Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer

An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer

Defined as the time from randomization to first documentation of disease progression per RECIST v1.1 by BICR, or to death due to any cause, whichever comes first.

OS is defined as the time from date of randomization to date of death due to any cause.

Defined as the proportion of subjects with confirmed CR or PR according to RECIST v1.1

Defined as the time from randomization to the first date a subject experiences a pain progression. Pain progression is defined as either an increase of 2 or more points from baseline on question 3 of the Brief Pain Inventory - Short Form (BPI-SF) or initiation of new opioid pain medication.

Using the BPI-SF question 3, mean change from baseline in worst pain will be calculated for each postbaseline assessment timepoint for Arm A and Arm B.

Defined as the time from randomization to first documentation of disease progression per RECIST v1.1, or to death due to any cause, whichever comes first

Defined as the time from first documented response of CR or PR (that is subsequently confirmed) to the first documented disease progression per RECIST v1.1, or to death due to any cause, whichever comes first

Defined as the proportion of subjects with confirmed CR, PR, or SD according to RECIST v1.1

The EQ-5D-5L is a standardized instrument developed by the EuroQol Group for use as a generic, preference-based measure of health outcomes. The EQ-5D-5L is a 5-item self-reported measure of functioning and wellbeing, which assesses 5 dimensions of health, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension comprises 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems). A unique EQ-5D-5L health state is defined by combining 1 level from each of the 5 dimensions. This questionnaire also records the respondent's self-rated health status on a vertical graduated (0 = the worst health a participant can imagine to 100 = the best health a participant can imagine) visual analogue scale.

EORTC-QLQ-C30 is a cancer-specific 30-item questionnaire. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

Descriptive statistics will be used to summarize results

Merck Sharp & Dohme LLC

Seagen Inc.

Astellas Pharma Global Development, Inc.

Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antibodies

Immunoglobulins

MRG002 will be administrated by an IV infusion of 2.6 mg/kg on Day 1 of every 3 weeks (21-day cycle).

MRG002

Program Director

Changlu Hu

Dexin Yu

Aipingv Zhou, MD

Ben Wan

Yinong Niu

Lijun Chen

Hong Luo

Yu Chen

Fangjian Zhou

Yongda Liu

Hongyu Zhang

Pei Lu

Hui Chen

Shujun Yang

Guiling Li

Minfeng Chen

Weiqing Han

Ziling Liu

Jizhong Quan

Cheng Fu

Guojun Chen

Benkang Shi

Danfeng Xu

Chuanliang Xu

Lei Li

Yong Liao

Xin Yao

Hailong Hu

Jimin Chen

Shaoxing Zhu

Zhiliang Weng

Aiping Zhou, MD

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG002 as single agent in patients with HER2-positive unresectable locally advanced or metastatic urothelium cancer.

The study consists of two stages. In Phase IIa, approximately 25 subjects will be enrolled to evaluate the safety and preliminarily efficacy of MRG002. Based on the initial safety and efficacy data obtained from the Phase IIa, the study design of second stage Phase IIb single-arm study either will be continued or the trail will be terminated. If the Phase IIa data support the continuation of the study, in the second stage, approximately an additional 33 subjects will be enrolled to further evaluate the efficacy and safety of MRG002.

A Study of MRG002 in the Treatment of HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer

An Open-label, Single-arm, Multi-center, Phase II Clinical Study of MRG002 in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer

ORR is defined as the percentage of patients with complete response (CR) and partial response (PR) as assessed by Independent Review Committee (IRC) according to RECIST v1.1.

ORR is defined as the percentage of patients with CR and PR as assessed by Investigator according to RECIST v1.1.

DOR is defined as the time from first documented objective response to the first onset of tumor progression or death of any cause.

TTR is defined as the duration from the start of treatment to the first onset of CR or PR in tumor evaluation.

DCR is defined as the percentage of patients who achieve CR, PR, and stable disease (SD) after treatment.

PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.

OS is defined as the duration from the start of treatment to death of any cause.

Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug.

Concentration-time curve will be depicted based on pharmacokinetics concentration set (PKCS).

The incidence of ADA analysis will be summarized for all patients who received at least one cycle study treatment.

Shanghai Miracogen Inc.

Respiratory Tract (Lung and Bronchial) Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Melanoma

Carcinoma, Renal Cell

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

Participants with melanoma received retifanlimab 500 milligrams (mg) every 4 weeks (Q4W), administered by intravenous (IV) infusion over 30 minutes on Day 1 of each 28-day cycle.

Participants with non-small cell lung cancer (NSCLC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle.

Participants with urethelial carcinoma (UC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle.

Participants with renal cell carcinoma (RCC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle.

Retifanlimab administered intravenously at 500 mg every 4 weeks

Retifanlimab

Mark Cornfeld, MD

The purpose of this study is to assess the clinical activity and safety of INCMGA00012 in participants with advanced solid tumors where the efficacy of PD-1 inhibitors has previously been established.

A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)

A Phase 2 Study of INCMGA00012 (PD-1 Inhibitor) in Participants With Selected Solid Tumors (POD1UM-203)

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by the investigator, at any post-Baseline visit until new anti-cancer therapy or first Progressive Disease. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

DOR was defined as the time from initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by the investigator, or death due to any cause. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

DCR was defined as the proportion of participants with an overall response of CR, PR, or stable disease (SD), per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

According to RECIST 1.1, PFS was defined as the length of time from the initial infusion of study drug until the earliest date of disease progression, determined by investigator assessment, or death due to any cause, if occurring sooner than progression.

Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause.

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of retifanlimab and until the earlier of 90 days of the last administration of retifanlimab and new anti-cancer therapy start if any, are reported.

Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab.

tmax was defined as the time to the maximum concentration of retifanlimab.

Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab.

AUC0-t was defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of retifanlimab.

Incyte Corporation

Treatment-emergent adverse events, defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of retifanlimab and until the earlier of 90 days of the last administration of retifanlimab and new anti-cancer therapy start if any, are reported.

Participants with melanoma received retifanlimab 500 milligrams (mg), administered by intravenous (IV) infusion over 30 minutes on Day 1 of each 28-day cycle (Q4W).

Participants with non-small cell lung cancer received retifanlimab 500 mg, administered by IV infusion over 30 minutes on Day 1 Q4W.

Non-small Cell Lung Cancer

Participants with urethelial carcinoma received retifanlimab 500 mg, administered by IV infusion over 30 minutes on Day 1 Q4W.

Urothelial Cancer

Participants with renal cell carcinoma received retifanlimab 500 mg, administered by IV infusion over 30 minutes on Day 1 Q4W.

Total

Urethelial Carcinoma

Age, Continuous

Sex: Female, Male

White/Caucasian

Asian

Not Reported

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Study Director

Full Analysis Set (FAS) Population: all study participants who had received at least 1 dose of study drug. Participants were to be analyzed based on disease-specific diagnosis. Confidence intervals were calculated based on the exact method for binomial distributions.

Overall Response Rate (ORR)

FAS Population. Only those participants with a CR or PR were included in the analysis. The 95% confidence interval was calculated using the Brookmeyer and Crowley's method and Klein and Moeschberger's method with log-log transformation.

Duration of Response (DOR)

FAS Population. Confidence intervals were calculated based on the exact method for binomial distributions.

Disease Control Rate (DCR)

FAS Population. Median PFS was estimated using the Kaplan-Meier method. The confidence interval for median PFS was calculated using the method of Brookmeyer and Crowley.

Progression-free Survival (PFS)

FAS Population. Median survival time in months was estimated using the Kaplan-Meier method. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.

Overall Survival

Safety Evaluable Population: all participants who received at least 1 dose of study drug

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

Participants with melanoma, non-small cell lung cancer, urethelial carcinoma, and renal cell carcinoma received retifanlimab 500 mg, administered by IV infusion over 30 minutes on Day 1 Q4W.

All Participants

Pharmacokinetic (PK) Evaluable Population: all participants who received at least 1 dose of study drug and provided a Baseline and at least 1 postdose PK sample

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Enfortumab Vedotin and Pembrolizumab vs. Chemotherapy Alone in Untreated Locally Advanced or Metastatic Urothelial Cancer	NCT04223856	Urothelial Canc...	Enfortumab vedo... Pembrolizumab Cisplatin Carboplatin Gemcitabine	18 Years -	Astellas Pharma Inc
A Study of MRG002 in the Treatment of HER2-positive Unresectable Locally Advanced or Metastatic Urothelium Cancer	NCT04839510	Locally Advance... Metastatic Urot...	MRG002	18 Years - 75 Years	Shanghai Miracogen Inc.
A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)	NCT03679767	Metastatic Non-... Locally Advance... Metastatic Urot... Unresectable Me... Metastatic Mela... Locally Advance... Metastatic Clea...	Retifanlimab	18 Years -	Incyte Corporation
A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer	NCT03288545	Carcinoma, Tran... Urinary Bladder... Urologic Neopla... Renal Pelvis Ne... Urothelial Canc... Ureteral Neopla... Urethral Neopla...	enfortumab vedo... pembrolizumab cisplatin carboplatin gemcitabine	18 Years -	Astellas Pharma Inc
A Single-Arm Study of Bempegaldesleukin (NKTR-214) Plus Nivolumab in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer	NCT03785925	Urinary Bladder... Neoplasm Metast...	Bempegaldesleuk... Nivolumab	18 Years -	Nektar Therapeutics
A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)	NCT03679767	Metastatic Non-... Locally Advance... Metastatic Urot... Unresectable Me... Metastatic Mela... Locally Advance... Metastatic Clea...	Retifanlimab	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for locally advanced urothelial cancer