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
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
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.
Single group
Sacituzumab Govitecan (SG)
DrugIntravenous infusion
Enfortumab vedotin-ejfv (EV)
DrugIntravenous infusion
Pembrolizumab
DrugIntravenous infusion
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.
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.
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.
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.
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination objective response rate (ORR)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination rate of complete responses (CR)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination rate of partial responses (PR)
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Sacituzumab Govitecan (SG) and Enfortumab Vedotin in combination rate of participants with progressive disease
Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
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Dana-Farber Cancer Institute
Lead sponsor
Gilead Sciences
Collaborator
