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35875211000001105

Refrigerated Storage

ImfinziAstraZeneca

AstraZeneca
Imfinzi
50 mg/mL concentrate for solution for infusion

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15 October 2021
London MI Service

New Medicines

ImfinziUnresectable non-small cell lung cancer (NSCLC) - lower frequency dosing regimen

Information

Imfinzi
New dosing regimen
AstraZeneca
AstraZeneca

Development and Regulatory status

Launched
Launched
Launched
January 2021
Jan 21New dosing regimen approved for use in the UK and EU. This allows for use of an additional dosing option of a 1,500 mg fixed dose, given every four weeks, for use as monotherapy for the treatment of locally advanced, unresectable NSCLC in adults whose tumours express PD-L1 on ≥ 1% of tumour cells and whose disease has not progressed following platinum-based chemoradiation therapy. The new dosing regimen has already been approved in the US [1,2].

Category

Antibody targeting PDL-1, a protein on tumour cells.
More than 39,000 new cases of lung cancer are diagnosed in the UK each year. NSCLC accounts for 85% of cases.
Unresectable non-small cell lung cancer (NSCLC) - lower frequency dosing regimen
Intravenous infusion

ImfinziAdvanced metastatic non-small cell lung cancer (NSCLC) (EGFR/ALK w/t) - first-line in combination with chemotherapy

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Feb 22Has been filed in the EU and US based on data from POSEIDON [7].
Dec 20Filings now expected H2 21 [4].
Jul 19Filings planned for H2 2019 based on POSEIDON [2].

Category

Antibody targeting PDL-1, a protein on tumour cells.
More than 39,000 new cases of lung cancer are diagnosed in the UK each year. NSCLC accounts for 85% of cases.
Advanced metastatic non-small cell lung cancer (NSCLC) (EGFR/ALK w/t) - first-line in combination with chemotherapy
Intravenous infusion

Trial or other data

May 21Company announces positive results of PIII POSEIDON trial final analysis which showed the combination of durvalumab + tremelimumab + chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit vs chemotherapy alone. It also demonstrated a statistically significant improvement in progression-free survival (PFS) vs chemotherapy alone. The durvalumab + chemotherapy arm did not achieve statistical significance for OS vs chemotherapy. Each combination demonstrated an acceptable safety profile, and no new safety signals were identified [6].
Dec 20PIII POSEIDON is recruiting again and collection of primary outcome data is expected to complete Apr 21 [4].
Nov 19PIII POSEIDON trial met a primary endpoint by showing a statistically significant and clinically meaningful improvement in the final PFS analysis in patients treated with the combination of Imfinzi and a broad choice of five standard-of-care platinum-based chemotherapy options vs. chemotherapy alone [3].
Aug 19PIII POSEIDON is active but no longer recruiting [1].
Jun 17PIII POSEIDON study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy + Standard of care (SoC) chemotherapy or durvalumab monotherapy + SoC chemotherapy versus SoC chemotherapy alone as first line treatment in patients with metastatic non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions starts (NCT03164616). 1000 patients will be recruited from sites including the US, EU & UK. Collection of primary outcome data (progression-free survival and overall survival) is due to complete Apr 21 [1].

Evidence based evaluations

ImfinziAdvanced metastatic non-small cell lung cancer (NSCLC) (EGFR/ALK w/t) - first-line in combination with tremelimumab and chemotherapy

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Feb 22Has been filed in the EU and US based on data from POSEIDON [9].
Dec 21Filed in EU via centralised procedure - assume for this indication [8].
Mar 20Filings planned for 2021 [4].
Jul 19Filings planned for H2 2019 based on POSEIDON [2].

Category

Durvalumab is an antibody targeting PDL-1, a protein on tumour cells. Tremelimumab is an antibody against CTLA-4.
More than 39,000 new cases of lung cancer are diagnosed in the UK each year. NSCLC accounts for 85% of cases.
Advanced metastatic non-small cell lung cancer (NSCLC) (EGFR/ALK w/t) - first-line in combination with tremelimumab and chemotherapy
Intravenous infusion

Trial or other data

Sep 22Exploratory analysis from PIII POSEIDON study found durvalumab plus tremelimumab added to chemotherapy demonstrated a sustained improvement in overall survival (25%) vs chemotherapy alone (13.6%). The risk of death was reduced by 38% for pts with STK11 mutation, 57% for KEAP1 mutation and 45% for KRAS mutation. The combination was well tolerated with no new safety signals identified during the approx 4 year follow up. Serious treatment-related adverse events of any grade occurred in 27.6% of pts in the durvalumab, tremelimumab and chemotherapy arm vs 17.7% for chemotherapy alone. Treatment-related adverse events leading to death occurred in 3.3% of pts taking the combination vs 2.4% for chemotherapy alone [10]
Sep 21IN POSEIDON study (n=675), durvalumab plus tremelimumab added to chemotherapy was associated with an improved PFS (6.2 v 4.8 months; p=0.00031) and OS (median 14 v 11.7 months; p=0.003) vs. chemotherapy alone [7].
May 21 Company announces positive results of PIII POSEIDON trial final analysis which showed the combination of durvalumab + tremelimumab + chemotherapy demonstrated a statistically significant and clinically meaningful overall survival (OS) benefit vs chemotherapy alone. It also demonstrated a statistically significant improvement in progression-free survival (PFS) vs chemotherapy alone. The durvalumab + chemotherapy arm did not achieve statistical significance for OS vs chemotherapy. Each combination demonstrated an acceptable safety profile, and no new safety signals were identified. [6]
Dec 20PIII POSEIDON is recruiting again and collection of primary outcome data is expected to complete Apr 21 [5].
Sep 19AstraZeneca announces positive data from PIII POSEIDON trial of durvalumab as monotherapy and in combination with tremelimumab for first-line treatment of stage IV non-small cell lung cancer; the company announced statistically significant and clinically meaningful improvement in the final progression-free survival result, compared to chemotherapy alone. The study will continue to assess the additional primary endpoint of overall survival [3].
Aug 19PIII POSEIDON is active but no longer recruiting [1].
Jun 17PIII POSEIDON study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy + Standard of care (SoC) chemotherapy or durvalumab monotherapy + SoC chemotherapy versus SoC chemotherapy alone as first line treatment in patients with metastatic non small-cell lung cancer (NSCLC) with tumors that lack activating epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions starts (NCT03164616). 1000 patients will be recruited from sites including the US, EU & UK. Collection of primary outcome data (progression-free survival and overall survival) is due to complete Apr 21 [1].

Evidence based evaluations

ImfinziAdvanced, unresectable hepatocellular carcinoma (HCC) - first-line with tremelimumab

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Pre-registration (Filed)
Launched
Oct 22FDA approves use of Imjudo (tremelimumab) in combination with durvalumab for the treatment of adults with unresectable HCC. The novel dose and schedule of the combination, which includes a single dose of Imjudo 300mg added to durvlumab 1500mg followed by durvalumab every four weeks, is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab) [17].
May 22Filed in EU via centralised procedure [16].
Apr 22FDA accepts a supplemental biologics license application (BLA) from AstraZeneca and granted a priority review of durvalumab with a single-dose of tremelimumab treating first-line HCC [15].

Category

Antibody targeting PDL-1, a protein on tumour cells.
The age-standardised incidence rate for liver cancer in the UK in 2008 was 4.3 per 100,000 population. In most cases, hepatocellular carcinoma (HCC) develops in patients with chronic liver disease (70-90% of all patients). HCC accounts for 90% of all liver cancers. Tumours are multifocal in the liver in 75% of cases at diagnosis [1].
Advanced, unresectable hepatocellular carcinoma (HCC) - first-line with tremelimumab
Intravenous infusion

Further information

Yes

Trial or other data

Jan 22In PIII HIMALYA study (n=753), a single priming dose of tremelimumab, plus durvalumab every 4 weeks, reduced risk of death vs. sorafenib by 22% (OS 16.4 vs 13.8 months; p<0.05). Objective response rate also improved (20.1% vs 5.1%) [14].
Nov 21PIII HIMALAYA is described as still recruiting, but states that collection of primary outcome data completed in Aug 21 [13].
Oct 21AstraZeneca reports improved survival in a phase 3 trial. The clinical trial linked tremelimumab-Imfinzi regimen to a statistically significant improvement in overall survival compared to sorafenib. Tremelimumab appears to be contributing to the benefits. They report the safety profile is favourable and found no evidence that use of tremelimumab increases severe liver toxicity [12].
Dec 20PIII HIMALAYA trial is recruiting again, and expects to finish collecting primary outcome data in Dec 21 [10].
May 20AstraZeneca report results from an open-label, multicentre, global PII study (Study 22; NCT02519348). In the primary endpoint of the trial evaluating safety, all experimental arms demonstrated an acceptable profile and no new safety signals were identified. Patients treated with a single, priming dose of tremelimumab 300mg added to durvalumab every four weeks (T300+D regimen) achieved a median overall survival (OS) of 18.7 months in a key secondary endpoint. In other key secondary endpoints, objective response rate (ORR) confirmed by independent central review was 24% with the T300+D regimen, and median duration of response (DoR) was not yet reached at the time of data cut-off [8].
Nov 19PIII HIMALAYA trial has finished recruiting [5].
Nov 18PIII HIMALAYA trial (NCT03298451) is recruiting; collection of primary outcome data due to complete Mar 20 [4].
Oct 17PIII HIMALAYA trial to evaluate the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable hepatocellular carcinoma starts (NCT03298451). The trial intends to enrol 1200 patients in Italy, Spain, Japan, South Korea, Russia and Ukraine. Primary endpoint is overall survival. Data are anticipated 2020 [2,3].

Evidence based evaluations

ImfinziHepatocellular carcinoma (HCC) - first-line monotherapy

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody targeting PDL-1, a protein on tumour cells.
The age-standardised incidence rate for liver cancer in the UK in 2008 was 4.3 per 100,000 population. In most cases, hepatocellular carcinoma (HCC) develops in patients with chronic liver disease (70-90% of all patients). HCC accounts for 90% of all liver cancers. Tumours are multifocal in the liver in 75% of cases at diagnosis [1].
Hepatocellular carcinoma (HCC) - first-line monotherapy
Intravenous infusion

ImfinziLocally advanced, unresected non-small cell lung cancer (NSCLC) - in combination with chemoradiation therapy

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Phase III Clinical Trials
None

Category

Antibody targeting PDL-1, a protein on tumour cells.
More than 39,000 new cases of lung cancer are diagnosed in the UK each year. NSCLC accounts for 85% of cases.
Locally advanced, unresected non-small cell lung cancer (NSCLC) - in combination with chemoradiation therapy
Intravenous infusion

Further information

Yes

Evidence based evaluations

Imfinzi Hepatocellular carcinoma (HCC), locoregional - in combination with transarterial chemoembolisation (TACE) +/- bevacizumab

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Phase III Clinical Trials
None
Yes

Category

Antibody targeting PDL-1, a protein on tumour cells.
The age-standardised incidence rate for liver cancer in the UK in 2008 was 4.3 per 100,000 population. In most cases, hepatocellular carcinoma (HCC) develops in patients with chronic liver disease (70-90% of all patients). HCC accounts for 90% of all liver cancers. Tumours are multifocal in the liver in 75% of cases at diagnosis [1].
Hepatocellular carcinoma (HCC), locoregional - in combination with transarterial chemoembolisation (TACE) +/- bevacizumab
Intravenous infusion

Further information

Yes
With bevacizumab and transarterial chemoembolisation for treating locally advanced hepatocellular carcinoma -Go to latest from NICE
With transarterial chemoembolisation for treating incurable locally advanced hepatocellular carcinoma -Go to latest from NICE

Evidence based evaluations

ImfinziNon-small cell lung cancer (NSCLC), stage IB, II or IIIA - adjuvant treatment following complete surgical resection

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Antibody targeting PDL-1, a protein on tumour cells.
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), stage IB, II or IIIA - adjuvant treatment following complete surgical resection
Intravenous infusion

Evidence based evaluations

Imfinzi Advanced bile duct cancer (cholangiocarcinoma) - first-line in combination with gemcitabine plus cisplatin

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Phase III Clinical Trials
Pre-registration (Filed)
Launched
Sep 22Approved in US for treatment of adult patients with locally advanced or metastatic biliary tract cancer in combination with gemcitabine/cisplatin chemotherapy [11].
May 22EMA begins its assessment of an application from AstraZeneca for a licence extension to include use in combination with chemotherapy for the treatment of adults with locally advanced or metastatic biliary tract cancer (BTC), based on the second interim analysis from the ongoing pivotal study D933AC00001 (TOPAZ-1) [10].
May 22US FDA grant Priority Review to its supplemental Biologics License Application for Imfinzi + standard-of-care chemotherapy with FDA action date for a regulatory decision set during Q3 2022. [9]
Dec 21Filings using TOPAZ-1 now expected H1 22 [6]
Dec 20Filings planned for >2021 [4].

Category

Antibody targeting PDL-1, a protein on tumour cells.
Cholangiocarcinoma arises from the cells within the bile ducts. It is often diagnosed late (stages III and IV) and the prognosis is poor. It is most common in those over 70 years old and is more common in men than women [1]. Incidence is 1-2 per 100,000 population per year in the UK [2].
Advanced bile duct cancer (cholangiocarcinoma) - first-line in combination with gemcitabine plus cisplatin
Intravenous infusion

Further information

Yes

Trial or other data

Jan 22In PIII TOPAZ-1 trial durvalumab, when given with chemotherapy, improved OS vs. chemotherapy alone (20% RR in risk of death) in those with advanced disease. A 25% reduction in risk of disease progression was also noted [8].
Dec 21PIII TOPAZ-1 is still recruiting; timescales unchanged [7].
Oct 21Independent Data Monitoring Committee concludes PIII TOPAZ-1 trial (n=685) meets primary endpoint of improved overall survival [5].
Nov 20PIII TOPAZ-1 trial is recruiting and due to finish collecting primary outcome data in Jun 22 [3].
Apr 19PIII TOPAZ-1 study to compare durvalumab with placebo in combination with gemcitabine and cisplatin in patients with 1st Line advanced BTC starts (NCT03875235). 757 adults will be recruited from countries including the UK, US and Europe. Primary outcome is overall survival [3].

ImfinziLocally advanced cervical cancer - with chemoradiotherapy followed by durvalumab maintenance

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Apr 22Development discontinued [7].

Category

Antibody targeting PDL-1, a protein on tumour cells.
There are around 3,200 new cervical cancer cases in the UK every year, 14th most common cancer in the UK [2].
Locally advanced cervical cancer - with chemoradiotherapy followed by durvalumab maintenance
Intravenous infusion

Further information

Yes

Trial or other data

Mar 22AstraZeneca announces durvalumab + chemotherapy failed to meet the primary endpoints in the PIII CALLA trial [6]

ImfinziHead and neck squamous cell carcinoma (HNSCC) - first-line monotherapy or in combination with tremelimumab

Information

Imfinzi
Licence extension / variation
AstraZeneca
AstraZeneca

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Feb 21Development discontinued [16].

Category

Monoclonal antibody targeting PDL-1, a protein on tumour cells, and CTLA-4.
There were approximately 8,000 new registrations for head and neck cancer in England and Wales in 2003, and 2,667 deaths in 2004. Less than 5% of people with head and neck cancer have metastatic disease at diagnosis. Approximately 20% of people with recurrent head and neck cancer have metastatic disease. Approximately 90% or all malignant tumours of the head and neck are squamous cell carcinomas [3].
Head and neck squamous cell carcinoma (HNSCC) - first-line monotherapy or in combination with tremelimumab
Intravenous infusion

Trial or other data

Feb 21Durvalumab fails to improve OS in PIII KESTREL trial [15].

Evidence based evaluations

1 December 2019NIHR
1 September 2018NIHR