Sacituzumab tirumotecan for Advanced urothelial carcinoma | Urothelial carcinoma

Inclusion criteria

• {"criterion_text":"- Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).\n- Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.\n- Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement are eligible.\n- PART 1 ONLY: Participants must have received platinum-based chemotherapy for treatment of la/mUC.\n- PART 1 ONLY: Participants must not have received >2 lines of therapy for la/mUC. Platinum-based chemotherapy followed by avelumab maintenance is considered 2 lines of therapy.\n- Not applicable: PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC."}

Exclusion criteria

• {"criterion_text":"- Known additional malignancy that is progressing or has required active treatment within the past 3 years.\n- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.\n- Not applicable: PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.\n- Not applicable: PART 2 ONLY: Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.\n- Is human immunodeficiency virus (HIV)-infected and has a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease.\n- Has active Hepatitis B or Hepatitis C virus infection.\n- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.\n- Has an active infection requiring systemic therapy.\n- Not applicable: PART 2 ONLY: History of allogeneic tissue/solid organ transplant.\n- Has not adequately recovered from major surgery or has ongoing surgical complications.\n- Known active central nervous system metastases and/or carcinomatous meningitis.\n- Has Grade ≥2 peripheral neuropathy.\n- Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.\n- Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea).\n- Has uncontrolled, significant cardiovascular disease or cerebrovascular disease and/or serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.\n- Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.\n- Has a history of uncontrolled diabetes.\n- Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration."}

Primary endpoints

• {"endpoint_text":"- Part 1: Percentage of Participants with Dose-limiting toxicities (DLT)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part 1: Percentage of Participants Who Experienced At Least One Adverse Event (AE)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Part 1: Percentage of Participants Who Discontinued Study Treatment Due to an AE","definition_or_measurement_approach":""}
• {"endpoint_text":"- Not applicable: Part 2: Percentage of Participants with DLT","definition_or_measurement_approach":""}
• {"endpoint_text":"- Not applicable: Part 2: Percentage of Participants Who Experienced At Least One AE","definition_or_measurement_approach":""}
• {"endpoint_text":"- Not applicable: Part 2: Percentage of Participants Who Discontinued Study Treatment Due to an AE","definition_or_measurement_approach":""}
• {"endpoint_text":"- Not applicable: Part 2: Objective Response Rate (ORR)","definition_or_measurement_approach":"ORR per RECIST 1.1 based on investigator assessment (as stated in main objectives)"}

Secondary endpoints

• {"endpoint_text":"- Part 1: ORR","definition_or_measurement_approach":"ORR per RECIST 1.1 based on investigator assessment"}
• {"endpoint_text":"- Not applicable: Part 2: Duration of Response (DOR)","definition_or_measurement_approach":"DOR per RECIST 1.1 based on investigator assessment"}
• {"endpoint_text":"- Part 1: Maximum Serum Concentration (Cmax) of Sacituzumab Tirumotecan-Antibody-Drug Conjugate (ADC)","definition_or_measurement_approach":"Cmax (PK parameter) for Sacituzumab Tirumotecan-ADC"}
• {"endpoint_text":"- Part 1: Serum Trough Concentration (Ctrough) of Sacituzumab Tirumotecan-ADC","definition_or_measurement_approach":"Ctrough (PK parameter) for Sacituzumab Tirumotecan-ADC"}
• {"endpoint_text":"- Part 1: Cmax of Free Payload for Sacituzumab Tirumotecan","definition_or_measurement_approach":"Cmax (PK parameter) of free payload"}
• {"endpoint_text":"- Part 1: Ctrough of Free Payload for Sacituzumab Tirumotecan","definition_or_measurement_approach":"Ctrough (PK parameter) of free payload"}
• {"endpoint_text":"- Part 1: Cmax of Enfortumab Vedotin-ADC","definition_or_measurement_approach":"Cmax (PK parameter) for Enfortumab Vedotin-ADC"}
• {"endpoint_text":"- Part 1: Ctrough of Enfortumab Vedotin-ADC","definition_or_measurement_approach":"Ctrough (PK parameter) for Enfortumab Vedotin-ADC"}
• {"endpoint_text":"- Part 1: Cmax of Free Payload for Enfortumab Vedotin","definition_or_measurement_approach":"Cmax (PK parameter) of free payload for Enfortumab Vedotin"}
• {"endpoint_text":"- Part 1: Ctrough of Free Payload for Enfortumab Vedotin","definition_or_measurement_approach":"Ctrough (PK parameter) of free payload for Enfortumab Vedotin"}
• {"endpoint_text":"- Part 1: Incidence of Antidrug Antibodies (ADA) to Sacituzumab Tirumotecan","definition_or_measurement_approach":"Incidence of ADA to Sacituzumab Tirumotecan (assessed per protocol assays)"}
• {"endpoint_text":"- Part 1: Incidence of ADA to Enfortumab Vedotin","definition_or_measurement_approach":"Incidence of ADA to Enfortumab Vedotin (assessed per protocol assays)"}
• {"endpoint_text":"- Not applicable: Part 2: Cmax of Sacituzumab Tirumotecan-ADC","definition_or_measurement_approach":"Cmax (PK parameter) for Sacituzumab Tirumotecan-ADC"}
• {"endpoint_text":"- Not applicable: Part 2: Ctrough of Sacituzumab Tirumotecan-ADC","definition_or_measurement_approach":"Ctrough (PK parameter) for Sacituzumab Tirumotecan-ADC"}
• {"endpoint_text":"- Not applicable: Part 2: Cmax of Free Payload for Sacituzumab Tirumotecan","definition_or_measurement_approach":"Cmax (PK parameter) of free payload"}
• {"endpoint_text":"- Not applicable: Part 2: Ctrough of Free Payload for Sacituzumab Tirumotecan","definition_or_measurement_approach":"Ctrough (PK parameter) of free payload"}
• {"endpoint_text":"- Not applicable: Part 2: Cmax of Enfortumab Vedotin-ADC","definition_or_measurement_approach":"Cmax (PK parameter) for Enfortumab Vedotin-ADC"}
• {"endpoint_text":"- Not applicable: Part 2: Ctrough of Enfortumab Vedotin-ADC","definition_or_measurement_approach":"Ctrough (PK parameter) for Enfortumab Vedotin-ADC"}
• {"endpoint_text":"- Not applicable: Part 2: Cmax of Free Payload for Enfortumab Vedotin","definition_or_measurement_approach":"Cmax (PK parameter) of free payload for Enfortumab Vedotin"}
• {"endpoint_text":"- Not applicable: Part 2: Ctrough of Free Payload for Enfortumab Vedotin","definition_or_measurement_approach":"Ctrough (PK parameter) of free payload for Enfortumab Vedotin"}
• {"endpoint_text":"- Not applicable: Part 2: Cmax of Pembrolizumab-ADC","definition_or_measurement_approach":"Cmax (PK parameter) for Pembrolizumab"}
• {"endpoint_text":"- Not applicable: Part 2: Ctrough of Pembrolizumab-ADC","definition_or_measurement_approach":"Ctrough (PK parameter) for Pembrolizumab"}
• {"endpoint_text":"- Not applicable: Part 2: Cmax of Free Payload for Pembrolizumab","definition_or_measurement_approach":"Cmax (PK parameter) of free payload for Pembrolizumab"}
• {"endpoint_text":"- Not applicable: Part 2: Ctrough of Free Payload for Pembrolizumab","definition_or_measurement_approach":"Ctrough (PK parameter) of free payload for Pembrolizumab"}
• {"endpoint_text":"- Not applicable: Part 2: Incidence of ADA to Sacituzumab Tirumotecan","definition_or_measurement_approach":"Incidence of ADA to Sacituzumab Tirumotecan (assessed per protocol assays)"}
• {"endpoint_text":"- Not applicable: Part 2: Incidence of ADA to Enfortumab Vedotin","definition_or_measurement_approach":"Incidence of ADA to Enfortumab Vedotin (assessed per protocol assays)"}
• {"endpoint_text":"- Not applicable: Part 2: Incidence of ADA to Pembrolizumab","definition_or_measurement_approach":"Incidence of ADA to Pembrolizumab (assessed per protocol assays)"}

France

Earliest CTIS Part Ii Submission Date

05-08-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

625

Number Of Sites

1

Number Of Participants

6

Denmark

Earliest CTIS Part Ii Submission Date

20-08-2024

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

609

Number Of Sites

1

Number Of Participants

1

Spain

Earliest CTIS Part Ii Submission Date

22-08-2024

Latest Decision Or Authorization Date

27-04-2026

Processing Time Days

613

Number Of Sites

2

Number Of Participants

9

Italy

Earliest CTIS Part Ii Submission Date

22-07-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

639

Number Of Sites

3

Number Of Participants

11

Netherlands

Earliest CTIS Part Ii Submission Date

05-06-2024

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

686

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Perceptive Eclinical Limited

Responsibilities

EUB Call center and medical escalation service

Name

Parexel International Corp.

Responsibilities

Medical information (Physician Consulting)

Name

Almac Clinical Technologies LLC

Name

Bioclinica Inc.

Responsibilities

Central imaging

Name

Q Squared Solutions Holdings LLC

Name

Ventana Medical Systems Inc.

Responsibilities

Tummor tissue

Third parties

• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"EUB Call center and medical escalation service","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"Medical information (Physician Consulting)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Q Squared Solutions Holdings LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"Tummor tissue","organisation_type":"Pharmaceutical company"}