First-line immunotherapy combination, nivolumab plus ipilimumab, demonstrates significant improvement in overall survival vs. chemotherapy in unresectable malignant pleural mesothelioma patients in a phase 3 trial

• CheckMate -743 is the first Phase 3 trial in which first-line immunotherapy treatment improved survival in

patients with malignant pleural mesothelioma

• With a minimum follow-up of 22 months, treatment with the investigational combination of nivolumab plus

ipilimumab demonstrated a median overall survival (OS) of 18.1 months vs. 14.1 months for platinum-based

chemotherapy1

• In the UK, 2,700 people are diagnosed with mesothelioma each year, of these, pleural mesothelioma accounts

for 90% of cases2

(Uxbridge, Middlesex, 8 August, 2020) – Bristol Myers Squibb today announced results from the Phase 3 CheckMate -743

trial, evaluating nivolumab plus low-dose ipilimumab, which met the primary endpoint of overall survival (OS) in

patients with unresectable malignant pleural mesothelioma (MPM), demonstrating a superior benefit versus

chemotherapy.1 These results (Abstract #3) were presented at the 2020 World Conference on Lung Cancer (WCLC)

Virtual Presidential Symposium hosted by the International Association for the Study of Lung Cancer on 8 August, 2020.1

With a minimum follow-up of 22 months, treatment with nivolumab plus ipilimumab reduced the risk of death by 26%,

demonstrating a median OS of 18.1 months vs 14.1 months for platinum-based chemotherapy (Hazard Ratio [HR]: 0.74

[95% Confidence Interval [CI]: 0.61, 0.89]; p=0.002).1

At two years, 41% of patients treated with the nivolumab plus ipilimumab combination were alive, compared to 27% of

patients treated with chemotherapy.1 These data establish nivolumab plus ipilimumab as the first immunotherapy

combination to reach its primary endpoint of OS in a MPM trial.

Histology is a well-established prognostic factor in mesothelioma, with non-epithelioid patients generally experiencing

poorer outcomes.3 In CheckMate -743, nivolumab plus ipilimumab showed directional improvements in survival across

both non-epithelioid and epithelioid MPM, with a larger magnitude of benefit observed in the non-epithelioid subgroup.

With the dual immunotherapy combination, median OS was 18.7 months for epithelioid patients and 18.1 months for

non-epithelioid patients, compared to 16.5 months and 8.8 months, respectively, with chemotherapy (epithelioid

subgroup HR: 0.86 [95% CI: 0.69, 1.08]; and non-epithelioid subgroup HR: 0.46 [95% CI: 0.31, 0.68]).1

The safety profile of nivolumab plus ipilimumab combination was consistent with the known profile of this combination

regimen, and no new safety signals were observed compared to previous studies of this combination. Grade 3-4

treatment-related adverse events were reported in 30.3% of patients treated with nivolumab plus ipilimumab and in

32% of patients treated with chemotherapy, and led to discontinuation in 15% of patients on nivolumab plus ipilimumab

and 7.4% of patients on chemotherapy.1

“The outcomes of the CheckMate -743 trial demonstrate the potential of a dual immunotherapy combination to support

patients with malignant pleural mesothelioma live longer versus chemotherapy,” said Faisal Mehmud, UK Country

Medical Director, Bristol Myers Squibb. “In rare cancers, such as mesothelioma, typically associated with a poor

prognosis, it is important that innovative treatments continue to be developed for these patients, where limited

options exist.”

Pleural mesothelioma is a rare type of lung cancer that starts in the layers of tissue that cover the lungs. In the UK,

2,700 people are diagnosed with mesothelioma each year, of these, pleural mesothelioma accounts for 90% of cases.2

There are three types of pleural mesothelioma, epithelioid mesothelioma is the most common type that grows more

slowly than others. Non-epithelioid mesotheliomas, including sarcomatoid and biphasic mesothelioma are less common

than epithelioid mesothelioma. Sarcamoatoid mesothelioma tends to progress more quickly than epithelioid

mesothelioma and biphasic mesothelioma is more aggressive than epithelioid mesothelioma but grows more slowly than

sarcomatoid mesothelioma.3 Exposure to asbestos is known to be implicated in most cases of pleural mesothelioma,

with around 90% of cases confirming that they have been in contact with asbestos.4

Only 5% of men, and 10% of women survive with mesothelioma for five years or more following diagnosis.5 Current

treatment options for mesothelioma patients in the UK include chemotherapy, radiotherapy, or surgery to remove the

cancerous tissue.6

About nivolumab

Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to harness the body’s

own immune system to help restore anti-tumour immune response.7 By harnessing the body’s own immune

system to fight cancer, nivolumab has become an important treatment option across multiple cancers.7

Nivolumab’s leading global development programme is based on Bristol Myers Squibb’s scientific expertise in

the field of Immuno-oncology and includes a broad range of clinical trials across all phases, including Phase III,

in a variety of tumour types. To date, the nivolumab clinical development programme has treated more than

35,000 patients. The nivolumab trials have contributed to gaining a deeper understanding of the potential role

of biomarkers in patient care, particularly regarding how people may benefit from nivolumab across the varied

levels of PD-L1 expression seen from patient-to-patient.

In Europe, nivolumab is licensed as monotherapy under the brand name Opdivo® for the:7

• Treatment of adult patients with advanced (unresectable or metastatic) melanoma**

• Adjuvant treatment of adults with melanoma with involvement of lymph nodes or metastatic disease

who have undergone complete resection

• Treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

after prior chemotherapy

• Treatment of adult patients with advanced renal cell carcinoma (RCC) after prior therapy**

• Treatment of adult patients with relapsed or refractory classical Hodgkin Lymphoma (cHL) after

autologous stem cell transplantation and treatment with brentuximab vedotin

• Treatment of adult patients with recurrent or metastatic squamous cell cancer of the head and neck

(SCCHN) in adults progressing on or after platinum-based therapy

• Treatment of adult patients with locally advanced unresectable or metastatic urothelial carcinoma in

adults after failure of prior platinum-containing therapy

**In addition, nivolumab is licensed in combination with ipilimumab for the treatment of adult patients with

advanced (unresectable or metastatic) melanoma, and as a first-line treatment of adult patients with

intermediate- and poor-prognostic risk advanced RCC.7

Nivolumab, as monotherapy or in combination with ipilimumab, increases the risk of severe immune-related

adverse reactions, which can include pneumonitis, colitis, hepatitis, nephritis and renal dysfunction,

endocrinopathies, skin reactions and other immune-related adverse reactions, as well as potential

complications of allogeneic haematopoietic stem cell transplant in classical Hodgkin Lymphoma.8

About ipilimumab

Cancer cells may exploit “regulatory” pathways, such as checkpoint pathways, to hide from the immune system and

shield the tumour from immune attack. Ipilimumab is a monoclonal antibody and immune checkpoint inhibitor that

targets non-redundant immune checkpoint pathways that regulate T cell differentiation and function.9

Ipilimumab is licensed in Europe as a monotherapy for adult patients with advanced (unresectable or metastatic)

melanoma.9

Ipilimumab increases the risk of severe immune-related adverse reactions, which can include diarrhoea, colitis,

hepatitis, skin inflammation, neurological adverse reactions, endocrinopathies, inflammation of the eyes and other

immune-related adverse reactions.10

Bristol Myers Squibb & Immuno-Oncology: Advancing Oncology Research

At Bristol Myers Squibb, patients are at the centre of everything we do. Our vision is to increase quality, longterm

survival for patients with cancer. Through a unique multidisciplinary approach powered by translational

science, we harness our deep scientific experience in oncology and I-O research, to identify novel treatments

tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline

designed to target different immune system pathways and address the complex and specific interactions

between the tumour, its microenvironment and immune system. We source innovation internally and in

collaboration with academia, government, advocacy groups and biotechnology companies, to help make the

promise of transformational medicines, like I-O, a reality for patients.