ASCO GU 2019: Sacituzumab Govitecan (IMMU-132) in Patients with Previously Treated Metastatic Urothelial Cancer

San Francisco, CA (UroToday.com) Sacituzumab govitecan (SG) is a humanized antibody-drug conjugate, made from anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.1 Trop-2 is transmembrane glycoprotein encoded by the Tacstd2 gene, and is differentially expressed in a wide range of tumor types, including gastric, pancreatic, triple-negative breast, colonic, prostate, and lung cancer.2 In hormone-receptor positive (HR+)/HER2- metastatic breast cancer (mBC), the overall response rate was 31% by local assessment, and the clinical benefit rate (PR+SD > 6 months) was 48%.3 In an early phase study with metastatic non-small cell lung cancer, 47 patients were treated and the objective response rate was 19% with a median response duration of 6.0 months.4 At GU ASCO 2017, Dr. Tagawa et al. reported the first 36 patients with metastatic UC who had been treated with Sacituzumab govitecan, and found an overall response rate of 31% with a median duration of response of 7.5 months in a heavily pre-treated population of patients with metastatic urothelial carcinoma. This abstract provides an update to this study. Patients have achieved a 31% objective response rate with a median overall survival not yet reached.

UroToday ASCOGU2019 IMMU13201BasketStudy
Summary
This is a phase I/II basket study of solid tumors who received SG on days 1 and 8 of 21-day cycles until progression or toxicity. Patients were radiographically restaged every 8 weeks. This abstract describes the 45 patients who were treated with SG.

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The median age was 67 and all patients had at least one prior line of systemic therapy. The majority of patients were men 41/45 and almost all patients (95%) had platinum-based chemotherapy previously. 38% of patients had been previously treated with a checkpoint inhibitor. This was a high risk population – 33/45 had visceral metastases, most commonly to the lung (15/45) and liver (27/45).

The median duration of follow up at the data cut-off was 15.7 months. Patients have had a median of 8 treatment cycles and 20% of patients have been treated for over one year. 5 patients remain on treatment, one of which was treated through progression and achieved a complete response.

The objective response rate was 31% overall, with 2/45 complete responses and 12 partial responses. In patients who had been previously treated with an immune checkpoint inhibitor, the ORR was 23% (4/17).  The median duration of response was 12.6 months and 2 patients remain on therapy for over 2 years.  The median overall survival was 18.9 months. 

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In terms of safety, the most common grade 3/4 adverse events were neutropenia (38%), anemia (11%), hypophosphatemia (11%), diarrhea (9%), fatigue (9%), and febrile neutropenia (7%). 5/45 patients discontinued treatment due to adverse events and no treatment-related deaths have been reported.
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Conclusions
SG is a promising new agent for patients with metastatic UC who have progressed after one line of therapy. The median OS described in this small study compares favorably to other second-line UC trials and a single arm, open label, global phase II study is underway to further evaluate safety and efficacy.


Presented by: Scott T. Tagawa, MD, MS, Weill Cornell Medicine, Assistant Professor of Medicine and Urology and Assistant Attending Physician in the Division of Hematology and Medical Oncology.

Written By: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, Twitter: @TheRealJasonZhu at the 2019 American Society of Clinical Oncology Genitourinary Cancers Symposium, (ASCO GU) #GU19, February 14-16, 2019 - San Francisco, CA

References:
  1. Cardillo TM, Govindan SV, Sharkey RM, et al. Sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody–drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers. Bioconjugate chemistry 2015;26:919-31.
  2. Shvartsur A, Bonavida B. Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes & cancer 2015;6:84.
  3. Bardia A, Diamond JR, Vahdat LT, et al. Efficacy of sacituzumab govitecan (anti-Trop-2-SN-38 antibody-drug conjugate) for treatment-refractory hormone-receptor positive (HR+)/HER2-metastatic breast cancer (mBC). American Society of Clinical Oncology; 2018.
  4. Heist RS, Guarino MJ, Masters G, et al. Therapy of advanced non–small-cell lung cancer with an SN-38-anti-trop-2 drug conjugate, sacituzumab govitecan. Journal of Clinical Oncology 2017;35:2790-7.
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