Sacituzumab Govitecan for Bile Duct Cancer
Palo Alto (17 mi)Overseen byAnup K Kasi Loknath Kumar
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Kansas Medical Center
No Placebo Group
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial tests how well sacituzumab govitecan works in treating patients with cholangiocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced), that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a toxic agent, called SN-38. HRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as TROP2 receptors, and delivers SN-38 to kill them.
Is the drug Sacituzumab Govitecan a promising treatment for Bile Duct Cancer?Sacituzumab Govitecan is a promising drug because it has shown effectiveness in treating various types of hard-to-treat cancers, like triple-negative breast cancer, by targeting cancer cells directly and delivering a powerful cancer-fighting agent.1451011
What safety data is available for Sacituzumab Govitecan?Safety data for Sacituzumab Govitecan, also known as Trodelvy or IMMU-132, is primarily derived from clinical trials involving patients with metastatic triple-negative breast cancer and other advanced solid tumors. In a phase I/II trial, safety was assessed in 408 patients with advanced solid tumors who received doses up to 10 mg/kg intravenously. Common adverse reactions occurring in 25% or more of patients included nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. These findings were part of the data supporting its FDA approval for metastatic triple-negative breast cancer.13569
What data supports the idea that Sacituzumab Govitecan for Bile Duct Cancer is an effective treatment?The available research does not provide specific data on Sacituzumab Govitecan for Bile Duct Cancer. Instead, it focuses on other treatments for this condition, such as combinations involving trastuzumab, tucatinib, panitumumab, and bevacizumab. These studies explore the effectiveness of these drugs in treating biliary tract cancers, particularly those with specific genetic markers like HER2 positivity. Without direct data on Sacituzumab Govitecan for Bile Duct Cancer, we cannot conclude its effectiveness based on the provided information.2781213
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you must stop all current medications. However, you cannot use other anti-cancer or investigational drugs during the study. If you're on high-dose corticosteroids or UGT1A1 inhibitors/inducers, you must stop them at least 2 weeks before starting the trial. Please consult with the trial team for guidance on your specific medications.
Eligibility Criteria
This trial is for patients with advanced forms of bile duct cancer, including those whose cancer has spread locally, returned after treatment, or metastasized. Participants must have measurable disease and be able to undergo procedures like biopsies and scans.Inclusion Criteria
I can take care of myself and am up and about more than half of the day.
My bile duct cancer has worsened or didn't respond to at least one treatment.
My kidneys are functioning well enough for treatment.
I am 18 years old or older.
Exclusion Criteria
I have a genetic variation linked to higher risk of side effects from irinotecan.
I have had serious heart issues or heart failure recently.
I have been treated with topoisomerase 1 inhibitors before.
I am on medication for an active infection but not just for prevention.
I have HIV with a detectable viral load.
I haven't had chemotherapy, biologics, or trial drugs within 4 weeks or 5 half-lives before starting the study drug.
I have not received any live vaccines in the last 30 days.
I am not using, nor plan to use other cancer treatments during this study.
Treatment Details
The trial is testing Sacituzumab Govitecan's effectiveness on cholangiocarcinoma. It involves a monoclonal antibody targeting TROP2 receptors on tumor cells to deliver the toxic agent SN-38 directly to them.
1Treatment groups
Experimental Treatment
Group I: Treatment (Sacituzumab govitecan)Experimental Treatment6 Interventions
Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy, PET/CT or MRI scans, and blood sample collection throughout the study.
Sacituzumab Govitecan is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Trodelvy for:
- Metastatic triple-negative breast cancer
- Locally advanced or metastatic urothelial cancer (withdrawn)
- Metastatic HR+/HER2- breast cancer
🇪🇺 Approved in European Union as Trodelvy for:
- Metastatic triple-negative breast cancer
🇨🇦 Approved in Canada as Trodelvy for:
- Metastatic triple-negative breast cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of Kansas Cancer CenterKansas City, KS
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Who is running the clinical trial?
University of Kansas Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022]Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers.
Therapeutic implication of HER2 in advanced biliary tract cancer. [2018]Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC.
Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. [2018]Sacituzumab govitecan (IMMU-132), an antitrophoblastic cell-surface antigen (anti-Trop-2) humanized antibody-SN-38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines the pharmacokinetics and safety of multiple cycles of IMMU-132 at doses of 8 or 10 mg/kg in patients with diverse advanced epithelial cancers.
Sacituzumab Govitecan: First Approval. [2021]Sacituzumab govitecan (sacituzumab govitecan-hziy; Trodelvy™) is a Trop-2-directed antibody conjugated to a topoisomerase I inhibitor (SN-38) that is being developed by Immunomedics for the treatment of solid tumours, including breast cancer. In April 2020, sacituzumab govitecan received accelerated approval in the USA for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Sacituzumab govitecan is undergoing phase III development for breast cancer in the USA and EU, and phase II development for urothelial cancer. It is also being explored for brain metastases, glioblastoma, endometrial cancer and prostate cancer. This article summarizes the milestones in the development of sacituzumab govitecan leading to this first approval for mTNBC.
Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]To review the pharmacology, efficacy, and safety of sacituzumab govitecan (-hziy; IMMU-132, Trodelvy) for patients with metastatic triple-negative breast cancer (mTNBC) who have received at least 2 prior therapies for metastatic disease.
FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. [2022]On April 22, 2020, the FDA granted accelerated approval to sacituzumab govitecan-hziy (TRODELVY; Immunomedics, Inc.) for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Approval was based on data from the IMMU-132-01 trial, a single-arm, multicohort, multicenter, phase I/II trial of sacituzumab govitecan. The assessment of efficacy was based on 108 patients with mTNBC who had previously received at least two prior lines of therapy in the metastatic setting and who received sacituzumab govitecan 10 mg/kg i.v. The assessment of safety was based on 408 patients with advanced solid tumors who had received sacituzumab govitecan at doses up to 10 mg/kg i.v. The primary efficacy endpoint was investigator-assessed objective response rate (ORR) and duration of response (DoR) was a key secondary endpoint. The ORR was 33.3% [36/108; 95% confidence interval (CI), 24.6-43.1], and median DoR among responders was 7.7 months (95% CI, 4.9-10.8). The most common adverse reactions occurring in ≥25% of patients were nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, rash, decreased appetite, and abdominal pain. This article summarizes the FDA review process and data supporting the approval of sacituzumab govitecan.
Randomized Phase II trial of combination chemotherapy with panitumumab or bevacizumab for patients with inoperable biliary tract cancer without KRAS exon 2 mutations. [2021]Biliary tract cancers (BTC) are rare and often diagnosed in late stages with advanced, nonresectable disease. The targeted agents panitumumab and bevacizumab have shown promising outcomes in combination with chemotherapy in other gastrointestinal (GI) cancers. We wanted to investigate if panitumumab or bevacizumab was the most promising drug to add to chemotherapy. Eighty-eight patients were randomized to combination chemotherapy supplemented by either panitumumab 6 mg/kg or bevacizumab 10 mg/kg on Day 1 in Arm A and Arm B, respectively. All patients received gemcitabine 1000 mg/m2 on Day 1, oxaliplatin 60 mg/m2 on Day 1 and capecitabine 1000 mg/m2 twice daily from Days 1 to 7. Treatment was repeated every 2 weeks until progression or for a maximum of 6 months. At progression, crossover was made to the other treatment arm. The primary endpoint was progression-free survival (PFS) at 6 months. With 19 of 45 in Arm A and 23 of 43 in Arm B PFS at 6 months, the primary endpoint was not met. The overall response rate (ORR) was 45% vs 20% (P = .03), median PFS was 6.1 months vs 8.2 months (P = .13) and median overall survival (OS) was 9.5 months vs 12.3 months (P = .47) in Arm A and Arm B, respectively. Our study showed no consistent differences between adding panitumumab or bevacizumab to chemotherapy in nonresectable BTC and none of the two regimens qualify for testing in Phase III. However, we found a higher response rate in the panitumumab arm with potential implication for future trials in the neoadjuvant setting.
Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. [2021]Systemic therapies for metastatic biliary tract cancers are few, and patients have a median overall survival of less than 1 year. MyPathway evaluates the activity of US Food and Drug Administration-approved therapies in non-indicated tumours with potentially actionable molecular alterations. In this study, we present an analysis of patients with metastatic biliary tract cancers with HER2 amplification, overexpression, or both treated with a dual anti-HER2 regimen, pertuzumab plus trastuzumab, from MyPathway.
Sacituzumab Govitecan for Treatment of Refractory Triple-Negative Metastatic Breast Cancer. [2021]Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. A confirmatory phase III trial evaluating sacituzumab govitecan vs. chemotherapy of the provider's choice was published in April 2021. Based on this trial, the FDA granted sacituzumab govitecan full regulatory approval. This antibody-drug conjugate is composed of a monoclonal antibody targeted at Trop-2 and contains the active metabolite of irinotecan, SN-38, as a cytotoxic side moiety. In a phase III clinical trial, sacituzumab govitecan demonstrated a median progression-free survival of 5.7 months vs. 1.7 months with chemotherapy. It is now an additional option for patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.
Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. [2023]Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) endocrine-resistant metastatic breast cancer is treated with sequential single-agent chemotherapy with poor outcomes. Sacituzumab govitecan (SG) is a first-in-class antibody-drug conjugate with an SN-38 payload targeting trophoblast cell-surface antigen 2, an epithelial antigen expressed in breast cancer.
An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023]Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets the human trophoblast cell-surface antigen 2 to deliver SN-38 to cancer cells. In this study, we assessed the efficacy and safety of SG in patients with relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC).
Tucatinib and Trastuzumab for Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Biliary Tract Cancer (SGNTUC-019): A Phase II Basket Study. [2023]To evaluate the efficacy and safety of tucatinib and trastuzumab in patients with previously treated human epidermal growth factor receptor 2-positive (HER2+) metastatic biliary tract cancer (mBTC).
Trastuzumab Plus Gemcitabine-Cisplatin for Treatment-Naïve Human Epidermal Growth Factor Receptor 2-Positive Biliary Tract Adenocarcinoma: A Multicenter, Open-Label, Phase II Study (TAB). [2023]Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs.