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Refrigerated Storage

YervoyBristol-Myers Squibb Pharmaceuticals Ltd

Bristol-Myers Squibb Pharmaceuticals Ltd
Yervoy
5mg/ml concentrate for solution for infusion

Contact Bristol-Myers Squibb Pharmaceuticals Ltd in all cases where a deviation from the recommended storage conditions has occurred. Refer to the current BNF for company contact details.

Please also refer to the manufacturer’s product literature for recommended storage information at https://www.medicines.org.uk

24 September 2021
London MI Service

New Medicines

YervoyNon-small cell lung cancer (NSCLC) in PD1 all-comers - first-line in combination with nivolumab and chemotherapy

Information

Yervoy
Licence extension / variation
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Launched
Launched
Launched
November 2020
Nov 20Approved in EU [3].
Sep 20Recommended for EU approval by CHMP - the additional indication is "in combination with nivolumab and 2 cycles of platinum-based chemotherapy ... for the first-line treatment of metastatic non-small cell lung cancer in adults whose tumours have no sensitising EGFR mutation or ALK translocation" [2].
May 20Approved in USA. Approval was based on data from a specified interim analysis from the PIII CheckMate -9LA trial [1].

Category

Human antibody against CTLA-4.
The incidence rate of lung cancer in 2006 was 72.2 per 100,000 in men and 50.8 per 100,000 in women. Lung cancer belongs to the three most common cancers in men (14.8 % of all cancers) and women (10.9% of all cancers).
Non-small cell lung cancer (NSCLC) in PD1 all-comers - first-line in combination with nivolumab and chemotherapy
Intravenous infusion

YervoyUnresectable pleural mesothelioma - first-line in combination with nivolumab

Information

Yervoy
Licence extension / variation
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Launched
Launched
Launched
July 2021
Jul 21Approved by MHRA for use in combination with nivolumab for the first line treatment of adult patients with unresectable malignant pleural mesothelioma [10].
Jun 21Approved in EU [9].
Apr 21Recommended for EU approval by CHMP - the additional indication is "nivolumab in combination with ipilimumab is indicated for the first line treatment of adult patients with unresectable malignant pleural mesothelioma.” [8].
Feb 21Granted Early Access to Medicines status (EAMS) for use in combination with nivolumab in the treatment of malignant pleural mesothelioma in adults [7].
Oct 20Nivolumab 360mg every three weeks plus ipilimumab 1 mg/kg every six weeks was approved by the U.S. FDA for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM) [6].
Sep 20Filed in EU via centralised procedure [5].

Category

Human antibody against CTLA-4.
The incidence of malignant pleural mesothelioma in males in the UK is 3.4 per 100,000. There are around 2,700 new cases in the UK each year. The incidence has increased slightly in the last decade. Exposure to asbestos is a well-established cause, with occupational exposure being documented in 70-80% of those affected [1].
Unresectable pleural mesothelioma - first-line in combination with nivolumab
Intravenous infusion

Further information

Yes

Trial or other data

Jan 21CheckMate 743 RCT (n=605) is published; it found nivolumab plus ipilimumab significantly extended overall survival vs chemotherapy (median overall survival 18·1 months vs 14·1 months, HR 0·74, p=0·0020). 2-year overall survival rates were 41% in the nivolumab plus ipilimumab group and 27% for chemotherapy [4].
Oct 16PIII CheckMate 743 trial to assess the efficacy and tolerability of the combination of nivolumab and ipilimumab, compared to pemetrexed and cisplatin or carboplatin, as a first-line therapy, in patients with unresectable pleural mesothelioma starts (NCT02899299). The primary endpoint is overall survival, assessed at 3.5 years. The randomised, open-label trial is designed to enrol approximately 600 patients in the UK, Eastern & Western Europe, North & South America and Africa. Collection of primary outcome data is due to complete Oct 20 [2,3].

Evidence based evaluations

YervoyDeficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) metastatic colorectal cancer - in combination with nivolumab

Information

Yervoy
Licence extension / variation
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Launched
Launched
Launched
July 2021
Jul 21Approved in the UK [7].
Jul 21Approved in EU [6].
May 21Yervoy is already licensed in the US for use in combination with nivolumab for treatment of adult and pediatric (12 years and older) patients with MSI-H or dMMR metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This was based on data from PII CheckMate-142 [5].
May 21Recommended for EU approval by CHMP – the new indication is Yervoy in combination with nivolumab is indicated for the treatment of adult patients with mismatch repair deficient or microsatellite instability high metastatic colorectal cancer after prior fluoropyrimidine based combination chemotherapy [2].

Category

Human antibody against CTLA-4.
Colorectal cancer is the second most common cause of cancer death in the UK. The age-standardised incidence rates for newly diagnosed cancers in England were 670.8 per 100,000 males and 546.1 per 100,000 females in 2014 [1].
Deficient Mismatch Repair (dMMR)/Microsatellite Instability High (MSI-H) metastatic colorectal cancer - in combination with nivolumab
Intravenous infusion

Trial or other data

Nov 20PIII CheckMate 8HW is still recruiting and collection of primary outcome data is now due to complete Aug 25 [4].
Jul 19PIII CheckMate 8HW to compare the clinical benefit, as measured by Progression-Free Survival (PFS), Objective Response Rate (ORR), and Overall Survival (OS), achieved by nivolumab in combination with ipilimumab or by nivolumab monotherapy in patients with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) metastatic colorectal cancer starts (NCT04008030). 494 adults will be recruited from sites around the world including US, EU & UK. Collection of primary outcome data (PFS) is expected to complete Oct 24 [3].

YervoyOesophageal cancer - first-line with nivolumab

Information

Yervoy
Licence extension / variation
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Phase III Clinical Trials
Recommended for approval (Positive opinion)
Pre-registration (Filed)
Feb 22Recommended for EU approval by CHMP – the extension to the existing indication is use in combination with nivolumab for the first-line treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥1% [8].
Sep 21FDA accepts the supplemental Biologics License Application for nivolumab in combination with ipilimumab as first-line treatment for adults with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of May 28, 2022 [7].
Aug 21Filed in EU for use in combination with nivolumab as first-line treatment for adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma (ESCC) [6].

Category

Human antibody against CTLA-4
In 2013, there were 8,784 new cases of oesophageal cancer in the UK: 5,852 (67%) in males and 2,932 (33%) in females, giving a male:female ratio of around 20:10. The crude incidence rate shows there are 19 new oesophageal cancer cases for every 100,000 males in the UK, and 9 for every 100,000 females [1].
Oesophageal cancer - first-line with nivolumab
Intravenous infusion

Further information

Yes

Trial or other data

Feb 22Results of CheckMate 648 reported in the NEJM [5].
Jun 21Results of CheckMate 648 reported at the American Society of Clinical Oncology (ASCO) meeting. Compared with chemotherapy alone, the combination of nivolumab plus chemotherapy reduced the risk of death by 26%, while the nivolumab plus ipilimumab combination reduced the risk by 22%. Both numbers are statistically significant and, as the study’s lead investigator, pointed out in a statement, are also clinically meaningful. These data were calculated at a median follow-up of 13 months. However, at 6 months, the results looked different with survival rates higher for the chemotherapy alone group vs nivolumab plus ipilimumab. The investigators are looking into possible reasons and patient characteristics to identify patients who may be more likely to die earlier with dual immuno-oncology therapy. Median survival time for patients on nivolumab plus chemotherapy was 15.4 months, vs 13.7 months for nivolumab plus ipilimumab and 9.1 months for chemotherapy alone. Improvements were more pronounced in patients whose tumours tested positive for the PD-L1 biomarker. In patients with PD-L1 expression of at least 1%, the death risk reduction rose to 46% for the nivolumab-chemo combination and to 36% for the nivolumab-ipilimumab combination [4].
Jun 17CheckMate 648 study to to compare how long subjects with esophageal cancer live overall or live without disease progression after receiving nivolumab and ipilimumab or nivolumab combined with fluorouracil plus cisplatin versus fluorouracil plus cisplatin starts (NCT03143153). 939 adults with histologically confirmed squamous cell carcinoma or adenosquamous cell carcinoma of esophagus will be recruited from sites in South America, Australia, the EU (incl UK) and Russia. Collection of primary outcome data (progression-free and overall survival) is expected to complete May 20 [2,3].

YervoyRefractory malignant melanoma - in combination with tilsotolimod

Information

Yervoy
Licence extension / variation
Bristol-Myers Squibb
Bristol-Myers Squibb

Development and Regulatory status

Discontinued
Discontinued
Discontinued
Yes
Sep 21Development discontinued [5].

Category

Human antibody against CTLA-4.
The UK incidence of malignant melanoma is about 21 per 100,000 people, and is doubling every 10-20 years [1].
Refractory malignant melanoma - in combination with tilsotolimod
Intravenous infusion

Trial or other data

Sep 21PIII ILLUMINATE-301 trial terminated due to lack of efficacy [5].