Sacituzumab Govitecan Plus EV in Metastatic UC
Combinations of Sacituzumab Govitecan Plus Enfortumab Vedotin and Pembrolizumab for Metastatic Urothelial Carcinoma: the Double Antibody Drug Conjugate (DAD) and Double Antibody Drug Conjugate With Immunotherapy (DAD-IO) Phase I/II Trial
1 other identifier
interventional
106
1 country
1
Brief Summary
Phase I of this research study will assess what doses of Sacituzumab Govitecan and Enfortumab Vedotin can be safely combined in the treatment of metastatic urothelial carcinoma (mUC). In Phase II of the study, patients in one of the two cohorts will receive Sacituzumab Govitecan, Enfortumab Vedotin, and Pembrolizumab to assess the efficacy of this drug combination. The names of the study drugs in these investigational combinations are:
- Enfortumab Vedotin
- Sacituzumab Govitecan
- Pembrolizumab
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2021
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2021
CompletedFirst Posted
Study publicly available on registry
January 26, 2021
CompletedStudy Start
First participant enrolled
May 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 1, 2028
November 4, 2025
November 1, 2025
5.7 years
January 20, 2021
November 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Maximum Tolerated Dose (MTD) of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination
The Maximum Tolerated Dose (MTD) in mg of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination is assessed.
21 days
Dose-limiting toxicity (DLT) of Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination
Treatment-Related Adverse Events are assessed by CTCAE v5.0 when administering Sacituzumab Govitecan (SG) and Enfortumab Vedotin (EV) in combination.
21 days
Efficacy of Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination
Study SG + EV combination to further refine the recommended dose and to assess the ORR (unconfirmed CR or PR) per RECIST Version 1.1 as determined by investigator for the combination of EV and SG in combination in patients with mUC progressing on platinum-based chemotherapy and PD1/L1 inhibitors.
21 days
Efficacy of Sacituzumab Govitecan (SG) and Enfortumab Vedotin and Pembrolizumab in combination
Study SG + EV + Pembrolizumab in combination to assess the ORR (unconfirmed CR or PR) per RECIST Version 1.1 as determined by investigator for the combination therapy of Pembrolizumab in combination with EV and SG in treatment-naïve patients with mUC.
21 days
Secondary Outcomes (11)
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination objective response rate (ORR)
21 days
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination rate of complete responses (CR)
21 days
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination rate of partial responses (PR)
21 days
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination rate of participants with progressive disease
21 days
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination overall survival (OS) Rate
21 days
- +6 more secondary outcomes
Study Arms (3)
Dose Escalation Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV)
EXPERIMENTALParticipants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of a 21-day study cycle. Dose escalation and de-escalation for the Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) combination will be guided using the Bayesian optimal interval (BOIN) design with up to 4 dose level escalations.
Dose Expansion Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV)
EXPERIMENTALParticipants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of each 21-day study cycle. Three dose levels of this drug combination will be studied with 3-18 patients per dose level depending on treatment-related dose limiting toxicities.
Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) and Pembrolizumab
EXPERIMENTALParticipants will be given a triplet regimen of Enfortumab Vedotin 1.25mg/kg, Sacituzumab Govitecan 7.5mg/kg (D1 and D8 every three weeks), and Pembrolizumab 200mg (D1 every 3 weeks) or 400 mg (D1 every 6 weeks) as a front-line therapy. Dose reductions of Enfortumab Vedotin to 1, 0.75 and 0.5 mg/kg will be permitted while Sacituzumab Govitecan can be dose reduced to 5 mg/kg. No dose reductions of Pembrolizumab are permitted. Following C1D1, drugs may be held independently per investigator discretion. A safety run-in will be conducted for the first 12 patients to evaluate the tolerability of the triplet regimen using Bayesian toxicity monitoring (BTOX). The first stage will enroll 6 patients, and if there are 2 or fewer DLTs, then next 6 patients will be enrolled. The study will be halted if there are 5 or more DLTs observed among the total of 12 evaluable patients.
Interventions
Intravenous infusion
Intravenous infusion
Intravenous infusion
Eligibility Criteria
You may qualify if:
- Participants must have histologically documented confirmed predominant urothelial carcinoma (i.e. of the bladder, renal pelvis, ureter or urethra). Patients with squamous differentiation or mixed cell types are eligible if the urothelial component is more than 50%; small-cell carcinoma is not allowed. Patients with locally advanced unresectable disease are eligible.
- Patient who are cisplatin eligible must have received prior treatment with platinum containing therapy defined as within the adjuvant/neoadjuvant setting with ≥ ypT2 disease at surgery or recurrent or progressive disease within 12 months or receiving treatment with platinum in locally advanced or metastatic setting. In addition, they must have received a checkpoint inhibitor (CPI) in locally advanced or metastatic urothelial cancer setting. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during or within 12 months of therapy completion are eligible. A CPI is defined as a PD-1 or PD-L1 inhibitor.
- Patients who are cisplatin-ineligible need only have progressed on or since one line of therapy defined as therapy given in the adjuvant/neoadjuvant setting within 12 months of progression or receiving therapy for locally advanced or metastatic disease
- Patient must be progressing on or since most recent therapy
- Age ≥18 years. Children are excluded from this study, but will be eligible for future pediatric trials.
- ECOG performance status 0-1.
- Participants must have adequate organ and marrow function as defined below:
- Leukocytes ≥3,000/mcL
- Absolute neutrophil count ≥1,500/mcL
- Platelets ≥100,000/mcL
- Total bilirubin ≤ institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤2.5x institutional ULN OR
- ≤5x ULN with liver metastases and serum albumin \> 3 g/dL
- Glomerular filtration rate (GFR) ≥30 mL/min/1.73 m2 (by Cockcroft Gault formula)
- Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- +8 more criteria
You may not qualify if:
- Women who are pregnant or lactating. Pregnant women are excluded from this study because SG and EV have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with EV or SG, breastfeeding should be discontinued if the mother is treated on protocol.
- Have had a prior anti-cancer biologic agent (including immune checkpoint inhibitors) within 4 weeks prior to Cycle 1 Day 1 (C1D1) or have had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to C1D1. Subjects participating in observational studies are eligible.
- Presence of any toxicities attributed to prior anti-cancer therapy that are not resolved to Grade 1 or baseline that could impose serious risk for complications before administration of study drug agent
- Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Have previously received topoisomerase 1 inhibitors, SG or EV
- Have an active second malignancy. Subjects with a history of malignancy that have been completely treated, with no evidence of active cancer for 3 years prior to start of therapy on trial (Cycle 1 Day 1 \[C1D1\]), or subjects with surgically-cured tumors with low risk of recurrence are allowed to enroll.
- Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to the first dose of study drug and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking ≤20 mg/day of prednisone or its equivalent. All subjects with carcinomatous meningitis are excluded regardless of clinical stability.
- Have active cardiac disease, defined as:
- Myocardial infarction or unstable angina pectoris within 6 months prior to C1D1
- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring anti-arrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation
- New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \< 40%
- Have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal (GI) perforation within 6 months of C1D1
- Have active serious infection requiring antibiotics (Contact sponsor-investigator for clarification)
- Have other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
- Patients with conditions requiring high doses of steroids (\>10 mg/day of prednisone or equivalent) or other immunosuppressive medications are excluded. Inhaled or topical steroids are permitted in the absence of active autoimmune disease.
- +55 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Dana-Farber Cancer Institutelead
- Gilead Sciencescollaborator
Study Sites (1)
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Related Publications (1)
McGregor BA, Sonpavde GP, Kwak L, Regan MM, Gao X, Hvidsten H, Mantia CM, Wei XX, Berchuck JE, Berg SA, Ravi PK, Michaelson MD, Choueiri TK, Bellmunt J. The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. Ann Oncol. 2024 Jan;35(1):91-97. doi: 10.1016/j.annonc.2023.09.3114. Epub 2023 Oct 21.
PMID: 37871703DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Bradley A McGregor, MD
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 20, 2021
First Posted
January 26, 2021
Study Start
May 20, 2021
Primary Completion (Estimated)
February 1, 2027
Study Completion (Estimated)
May 1, 2028
Last Updated
November 4, 2025
Record last verified: 2025-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data can be shared no earlier than 1 year following the date of publication
- Access Criteria
- Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.