dm+d

40099811000001106

Refrigerated Storage

Trodelvy Gilead Sciences

Gilead Sciences
Trodelvy
180 mg powder for concentrate for solution for infusion

Contact Gilead Sciences in all cases where a deviation from the recommended storage conditions has occurred. Refer to the electronic medicines compendium (eMC) at https://www.medicines.org.uk for company contact details.

23 February 2022
London MI Service

New Medicines

Trodelvy Relapsed/refractory triple-negative breast cancer

Information

Trodelvy
New molecular entity
Gilead Sciences
Immunomedics

Development and Regulatory status

Launched
Launched
Launched
November 2021
Nov 21Approved in EU [22]
Nov 21Trodelvy 180mg powder concentrate for solution for infusion launched in the UK. Price for 1 vial is £793.00 [21].
Oct 21Recommended for EU approval by CHMP “treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease”. Trodelvy will be available as a 200mg powder for concentrate for solution for infusion [20].
Sep 21Approved in the UK for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior lines of systemic therapies, at least one of them given for unresectable locally advanced or metastatic disease [19].
Apr 21With key patient survival data from the PIII Ascent trial, the FDA has now given full approval for sacituzumab govitecan in the US for treatment of locally advanced or metastatic triple-negative breast cancer (TNBC) after at least two prior therapies. The final indication marks a step up from the original conditional accelerated approval, which was based on tumour shrinkage and duration of response data. The original approval was for TNBC after at least two prior therapies for metastatic disease, but the final approval requires only one of the two prior treatments to be for metastatic disease [16].
Mar 21EMA validates MAA for treatment of metastatic triple-negative breast cancer [15].
Oct 20Gilead buys Immunomedics [14].
Aug 20Company plans to file to EMA in H1 21 [14].
May 20Launched in US [14].
Apr 20Approved in US [12].
Apr 20A biologics license application resubmission seeking accelerated approval of sacituzumab govitecan for the treatment of patients with mTNBC who have received at least two prior therapies for metastatic disease is under U.S. FDA review, with a PDUFA target action date of June 2, 2020 [11].
Feb 20Analysts predict this will be one of the top 10 most-anticipated new US drug launches of 2020 based on estimated global sales in 2024 [10].
Jan 20According to its 2018 annual report, Immunomedics plans to bring sacituzumab govitecan to the US market on its own for patients with mTNBC. European operations are headquartered in Rodermark, Germany, but Immunomedics has no current distribution agreements in place for Europe [9].
Dec 19Immunomedics have resubmitted their BLA to the FDA seeking accelerated approval of sacituzumab govitecan for the treatment of patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease [7].
Jan 19In the US, Immunomedics has received a complete response letter (CRL) from the FDA rejecting the BLA for sacituzumab govitecan. The company have issued the statement "The issues related to approvability in the CRL were exclusively focused on Chemistry, Manufacturing and Control matters and no new clinical or preclinical data need to be generated" and will work with the FDA to gain approval [6].
Jul 18US FDA accepts the Biologics License Application (BLA) and grants priority review for sacituzumab govitecan for treatment of patients with mTNBC who previously received at least two prior therapies for metastatic disease. The PDUFA target action date is January 18, 2019. The submission is based on data from a PI/II trial [5].
Nov 17Immunomedics reports that, following a successful pre-BLA meeting with the US FDA, the company is on track to submit file for accelerated approval in patients with metastatic TNBC in the US in Q1 18 [4].
Feb 16FDA grants breakthrough therapy designation to sacituzumab govitecan for treatment of patients with triple-negative breast cancer (TNBC) who have failed at least 2 prior therapies for metastatic disease [1].

Category

An antibody-drug conjugate comprising hRS7, a humanised antibody that binds to the trophoblast cell-surface antigen (TROP-2), and SN-38 which is the active metabolite of irinotecan.
Triple-negative breast cancer does not express receptors for oestrogen, progesterone, or Her2; it accounts for between 10% and 20% of all breast cancers. TNBC is regularly reported to be three times more common in women of African descent and in pre-menopausal women, and carries a poorer prognosis than other forms of breast cancer [3].
Relapsed/refractory triple-negative breast cancer
Intravenous

Further information

Yes

Trial or other data

Apr 21PIII ASCENT trial showed a significant 57% decrease in risk of disease worsening or death (PFS) in pts taking Sacituzumab govitecan-hziy. The drug extended median PFS to 4.8 months from 1.7 months for chemotherapy. It also increased median OS to 11.8 months vs 6.9 months which was a 49% reduction in risk of death. [17]
Apr 21Apr 21: Results of PIII ASCENT RCT reported in NEJM [18].
Jul 20Sacituzumab govitecan-hziy met its primary endpoint of PFS in the PIII ASCENT trial in pts with metastatic triple-negative breast cancer (mTNBC) who have previously received >2 prior therapies (median PFS was 5.6 months with Sacituzumab vs. 1.7 months for std of care chemotherapy. However, sacituzumab has a black box warning for severe neutropenia and diarrhea and can cause other side effects including nausea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash and abdominal pain.[13]
Apr 20PIII confirmatory ASCENT study will be halted due to compelling evidence of efficacy. This decision was based on the unanimous recommendation by the independent Data Safety Monitoring Committee (DSMC), during its recent routine review of the study [11].
Dec 18Immunomedics reports results from a PI/II study (NCT02161679) at the 2018 SABCS, confirming that monotherapy with sacituzumab govitecan achieved an objective response rate (ORR) of over 30 percent among heavily pre-treated patients with metastatic triple-negative breast cancer (mTNBC), with a manageable safety profile. With an additional 5 months of follow-up for the previously reported mTNBC patient cohort, sacituzumab govitecan monotherapy continued to demonstrate robust clinical activity with an ORR of 33% and 34% based on local assessment and blinded independent central review (BICR), respectively [5].
Apr 18FDA agrees under a Special Protocol Assessment (SPA) to the company ´s proposed amendments to the confirmatory ASCENT trial protocol, and increased the sample size to 488 patients. The protocol amendment also includes an interim analysis based on ORR that is expected to form the basis of an accelerated approval submission. The amendments incorporated recommendations from EU National Health authorities and advice from key breast cancer experts [8].
Oct 17PIII registrational ASCENT trial to assess the safety and efficacy of sacituzumab govitecan in patients with relapsed or refractory TNBCstarts (NCT02574455). This randomised, open-label trial is enrolling approximately 328 patients in the US [4].
Feb 16PIII trial identified but not yet recruiting; NCT02574455 is an international, multi-center, open-label, randomized, Phase III study in patients with metastatic TNBC refractory or relapsing after at least 2 prior chemotherapies (including a taxane) for their metastatic disease. Patients will be randomised to either sacituzumab govitecan or treatment of physician choice selected prior to randomization from one of the 4 allowed regimens. Primary outcome is progression-free survival and estimated primary completion date June 2020 [2].

Evidence based evaluations

Trodelvy HR-positive HER2-negative metastatic breast cancer - in patients who have failed at least 2 prior chemotherapy regimens

Information

Trodelvy
Licence extension / variation
Gilead Sciences
Immunomedics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Pre-registration (Filed)
Oct 22FDA grants priority review to the US licence application for use in heavily pre-treated HR-positive, HER2-negative breast cancer, with an approval action date of Feb 23 [9].
Aug 22Filed in the US for HR-positive, HER2-negative disease [6].

Category

An antibody-drug conjugate comprising hRS7, a humanised antibody that binds to the trophoblast cell-surface antigen (TROP-2), and SN-38 which is the active metabolite of irinotecan.
There are around 55,200 new breast cancer cases in the UK every year (2014-2016). 70% are oestrogen/hormone receptor-positive and 85% are HER2-negative [1].
HR-positive HER2-negative metastatic breast cancer - in patients who have failed at least 2 prior chemotherapy regimens
Intravenous

Further information

Yes

Trial or other data

Sep 22In data reported from the TROPiCS-02 trial at ESMO 2022, Trodelvy extended patients lives by a median 3.2 months over physician choice of chemotherapy in heavily pretreated HR-positive, HER2-negative breast cancer (median OS 14.4 months, versus 11.2 months for the chemo group), which translates to a 21% death risk reduction [8].
Sep 22PIII TROPiCS-02 RCT (NCT03901339; n=543) found sacituzumab (SG) significantly reduced risk of progression or death by 34% vs chemotherapy (HR 0.66, 95% CI 0.53-0.83; p=0.0003). Key grade ≥3 treatment-related AE’s (SG vs chemotherapy) were neutropenia (51% vs 38%) and diarrhoea (9% vs 1%) [7].
Aug 22Gilead announces that, at the second interim analysis of overall survival in the phase 3 TROPiCS-02 trial, Trodelvy produced a statistically significant and clinically meaningful improvement. The second interim analysis was set to occur after 350 deaths, after an additional 20% deaths had occurred since the first interim analysis [6].
Jun 22Data from the PIII TROPiCS-02 trial presented at ASCO. In heavily pre-treated patients with HR+/HER2-breast cancer, Trodelvy reduced the risk of disease progression or death by a statistically significant 34% vs. physician choice of chemotherapy. However, patients who received Trodelvy went a median 5.5 months without tumour progression, only 1.5 months more than the median 4 months in the chemotherapy arm of the trial. At 12 months, 21% of Trodelvy patients were still alive without disease progression, versus 7% for the chemo group. In multiple subgroup analyses, Trodelvy showed a PFS benefit in all but three groups [5].
Mar 22Company announces sacituzumab govitecan-hziy met its primary endpoint with a statistically significant improvement in progression-free survival vs TPC in the PIII TROPiCS-02 study. The safety profile for sacituzumab govitecan-hziy was consistent with prior studies, and no new safety concerns were identified [4].
Jun 21PIII TROPiCS-02 study is active but no longer recruiting [2].
May 19PIII TROPiCS-02 study to assess and compare the efficacy and safety of sacituzumab govitecan-hzi versus treatment of physician´s choice (TPC) in participants with hormonal receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC) starts (NCT03901339). Participants will receive sacituzumab govitecan-hziy 10 mg/kg via intravenous (IV) injection administered on Day 1 and Day 8 of a 21-day cycle, or will receive TPC determined prior to randomization from one of the following single-agent treatment (eribulin, capecitabine, gemcitabine or vinorelbine). 543 adults will be recruited including in the UK, US, Europe and other countries. Primary outcome is progression-free survival; collection of these data is due to complete Nov 21 [2].

Evidence based evaluations

Trodelvy Metastatic urothelial cancer

Information

Trodelvy
Licence extension / variation
Gilead Sciences
Immunomedics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Launched
Apr 21Approved by US FDA. [6,7]
Mar 21Gilead has filed for accelerated approval in the US [5].
Apr 20US FDA grants Fast Track designation for sacituzumab govitecan for treatment of adults with locally advanced or metastatic urothelial cancer (mUC) who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting, including patients who are platinum ineligible and have previously received a PD-1 or PD-L1 inhibitor in the neoadjuvant/adjuvant, locally advanced, or metastatic setting [4].

Category

Antibody-drug conjugate (ADC)
Bladder cancer is the 4th most common cancer in men and the 11th most common in women. The overall incidence in the UK is 11.4 per 100,000 population [2].
Metastatic urothelial cancer
Intravenous

Further information

Yes

Trial or other data

Oct 21PIII TROPiCS-04 trial is recruiting. Collection of primary outcome data now expected to finish Jun 23 [8].
Apr 21Interim data (n=112) from PII TROPHY study showed 27.7% of those treated with Trodelvy responded, with 5.4% experiencing a complete response and 22.3% experiencing partial response. The median duration of response was 7.2 months (95% CI: 4.7-8.6). [6]
Nov 20PIII TROPiCS-04 trial of sacituzumab govitecan versus treatment of physician choice in subjects with metastatic or locally advanced unresectable urothelial cancer who have progressed after prior therapy with platinum-based regimen and anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy starts (IMMU-132-13; NCT04527991). 482 adults will be recruited in the US and Puerto Rico. Primary outcome is overall survival; collection of these data is expected to complete Apr 23 [3].
Oct 20PII TROPHY U-01 study (NCT03547973) is recruiting 201 patients in the US and France and expects to complete collection of primary outcome data in Sep 21 [3].
Sep 20PII TROPHY U-01 study of sacituzumab govitecan in metastatic urothelial cancer results show this has significant activity and is safe in patients with heavily-pretreated mUC who progressed on both platinum-based chemotherapy and checkpoint inhibitors. Overall response rate was 27% (95% CI 19- 37). Median overall survival was 10.5 months[1].

Evidence based evaluations

TrodelvyNon-small cell lung cancer (NSCLC) - second- or third-line

Information

Trodelvy
Licence extension / variation
Gilead Sciences
Immunomedics

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

An antibody-drug conjugate comprising hRS7, a humanised antibody that binds to the trophoblast cell-surface antigen (TROP-2), and SN-38 which is the active metabolite of irinotecan.
More than 39,000 new cases of lung cancer are diagnosed in the UK each year. NSCLC accounts for 85% of cases.
Non-small cell lung cancer (NSCLC) - second- or third-line
Intravenous

TrodelvyAdvanced triple-negative breast cancer, PD-L1-negative - first-line monotherapy

Information

Trodelvy
Licence extension / variation
Gilead Sciences
Immunomedics

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

An antibody-drug conjugate comprising hRS7, a humanised antibody that binds to the trophoblast cell-surface antigen (TROP-2), and SN-38 which is the active metabolite of irinotecan.
Triple-negative breast cancer does not express receptors for oestrogen, progesterone, or Her2; it accounts for between 10% and 20% of all breast cancers. TNBC is regularly reported to be three times more common in women of African descent and in pre-menopausal women, and carries a poorer prognosis than other forms of breast cancer [1].
Advanced triple-negative breast cancer, PD-L1-negative - first-line monotherapy
Intravenous infusion

TrodelvyAdvanced triple-negative breast cancer, PD-L1-positive - first-line with pembrolizumab

Information

Trodelvy
Licence extension / variation
Gilead Sciences
Immunomedics

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

An antibody-drug conjugate comprising hRS7, a humanised antibody that binds to the trophoblast cell-surface antigen (TROP-2), and SN-38 which is the active metabolite of irinotecan.
Triple-negative breast cancer does not express receptors for oestrogen, progesterone, or Her2; it accounts for between 10% and 20% of all breast cancers. TNBC is regularly reported to be three times more common in women of African descent and in pre-menopausal women, and carries a poorer prognosis than other forms of breast cancer [1].
Advanced triple-negative breast cancer, PD-L1-positive - first-line with pembrolizumab
Intravenous infusion