This website is intended for healthcare professionals only.

Hospital Healthcare Europe
Hospital Pharmacy Europe     Newsletter    Login            

Press Releases

Take a look at a selection of our recent media coverage:

Nivolumab-relatlimab approved by MHRA for advanced melanoma

3rd January 2024

The combined cancer treatment nivolumab-relatlimab (brand name Opdualag) has been granted marketing authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA) for advanced melanoma.

The monoclonal antibody treatment manufactured by Bristol-Myers Squibb is now approved for adults and children from the age of 12 years.

Administered via a drip over 30 minutes every four weeks in a hospital under specialist medical supervision, nivolumab-relatlimab is continued for as long as clinical benefit is observed by the doctor, or until side effects become too severe.

Nivolumab attaches to the target protein PD 1 and relatlimab to LAG-3, blocking their actions and helping to increase T-cell activity against the melanoma.

This nivolumab-relatlimab approval was granted through Project Orbis, a global partnership between the MHRA, the Therapeutics Goods Administration in Australia, Health Canada, the Health Sciences Authority in Singapore, Swissmedic, Agência Nacional de Vigilância Sanitária in Brazil and Israel’s Ministry of Health, coordinated by the US Food and Drug Administration. 

This programme reviews and approves promising cancer drugs, helping patients to access treatments more quickly.

Nivolumab-relatlimab and progression-free survival

The Project Orbis decision on nivolumab-relatlimab was based on the results of a phase 2/3 randomised, double-blind clinical trial involving 714 patients with previously untreated advanced melanoma.

Patients were given either 480 mg nivolumab with 160 mg of relatlimab, or 480mg of nivolumab alone, every four weeks.

The primary endpoint was progression-free survival as assessed by blinded independent central review.

The researchers concluded that the combined nivolumab-relatlimab treatment was more effective at slowing the progression of the disease over those given nivolumab alone.

The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with nivolumab-relatlimab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab alone (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P=0.006 by the log-rank test).

Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with nivolumab-relatlimab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab alone.

Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients in the nivolumab-relatlimab group and in 9.7% of patients in the nivolumab group.

The most common adverse events experienced with nivolumab-relatlimab were tiredness; pain in muscles, bones and joints; skin rash (sometimes with blisters) and itching; decreased appetite; headache; diarrhoea; constipation; nausea; vomiting; stomach pain; fever; cough; difficulty breathing; underactive thyroid gland; skin colour change in patches (vitiligo); urinary tract infection; and decreased number of red and white blood cells.

In September 2023, nivolumab (brand name Opdivo) was approved by the European Commission for use as a monotherapy for the adjuvant treatment of stage IIB or IIC melanoma.

Potential for faecal microbiota transplantation to enhance immunotherapy in advanced melanoma

11th July 2023

A faecal microbiota transplantation (FMT) from healthy donors prior to PD-1 inhibitor immunotherapy could represent a novel and effective approach to the management of advanced melanoma, according to a recent phase 1 trial.

Published in the journal Nature Medicine, researchers combined healthy donor FMT with the PD-1 inhibitors nivolumab or pembrolizumab in previously untreated patients with advanced melanoma.

The primary outcome of interest was safety, with key secondary endpoints of the objective response rate, changes in gut microbiome composition and systemic immune and metabolomics analyses.

A total of 20 patients with a confirmed diagnosis of unresectable or metastatic cutaneous melanoma and with no previous anti-PD-1 treatment were enrolled.

Patients received a single FMT via capsules containing 80-100 mg of faeces from heavily screened healthy donors. Individuals were required to consume 36-40 capsules under supervision followed by a 30-minute period of observation.

Faecal microbiota transplantation ‘safe and effective’

When considering the primary outcome, eight patients experienced grade 1-2 FMT-related toxicities, mainly diarrhoea, flatulence and abdominal discomfort. However, there were no grade 3 or higher adverse events before receipt of the first dose of anti-PD-1 therapy.

The objective response rate was 65% and this included four patients who experienced a complete response. Microbiome profiling revealed that all of the patients engrafted strains from their respective donors although the acquired similarity between microbiomes increased over time in responders.

The researchers concluded that FMT from healthy donors represents a safe new therapeutic tool that has clinical potential and should be explored further in randomised trials.

Additional approaches are needed in advanced melanoma given that five-year survival even with combination immunotherapy is just over 50%. Previous work suggested that FMT and anti-PD-1 therapy, could overcome resistance to anti-PD-1.

Objective response rate in advanced melanoma improved when vitamin D level normal

3rd May 2023

The objective response and progression-free survival rates in advanced melanoma are greater when vitamin D levels are within the normal range

Vitamin D can modulate both innate and adaptive immune responses. Moreover, recent work suggests that vitamin D exerts anti-proliferative effects on tumour cells. Some research also demonstrates how the vitamin up-regulates programmed death ligand 1 expression. This findings indicates a possible synergic effect in combination with immune-checkpoint inhibitor treatment. But whether this improves the objective response rate during advanced melanoma treatment remains unclear.

The current study looked at the effect of vitamin D levels during anti-PD-1 immunotherapy with nivolumab or pembrolizumab in advanced, inoperable or metastatic melanoma. Serum levels of vitamin D were either reduced (group 1) or normal (group 2). Researchers then compared the objective response rate, progression-free and overall survival between the two groups.

Objective response rate and vitamin D levels

Data were available for 200 patients. Among those in group 1, the objective response rate (ORR) was significantly lower than for group 2 (36.2% vs 56%, p = 0.011). Similarly, there was a shorter progression-free survival (5.75 vs 11.25 months, p = 0.037). In addition, a lower proportion of patients had a complete response (7.8% vs 10.3%). Finally, the overall survival was lower in group 1 but the difference with group 2 was non-significant (27 vs 31.5 months, p = 0.39).

The researchers suggest that vitamin D levels should be within the normal range during anti-PD-1 immunotherapy in advanced melanoma patients.

mRNA-4157/V940 vaccine effective in advanced melanoma

21st December 2022

mRNA-4157/V940 which represents a personalised cancer vaccine has been found effective when combined with pembrolizumab in advanced melanoma

Moderna, in conjunction with Merck, has found that the investigational, personalised cancer vaccine, mRNA-4157/V940, combined with pembrolizumab, was more effective than pembrolizumab alone at reducing the risk of death or recurrence in patients with stage III/IV melanoma following complete resection.

Melanoma of the skin is the 17th most common cancer worldwide with 324,635 new cases and 57,043 deaths in 2020. Although patients diagnosed at Stage 1 have an excellent prognosis, this drops significantly as the disease spreads. For example, regional melanoma (stage 3) has a 63.6% 5-year survival and this drops to 22.5% for those with stage 4 (metastatic) disease.

Pembrolizumab (brand name Keytruda) is a human, programmed death receptor-1 (PD-1) therapy and works to enable T cells to invade melanoma anywhere in the body. The drug is already licensed as monotherapy for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma.

The KEYNOTE-942 study is an on-going phase 2b randomised study designed to assess whether postoperative adjuvant therapy with mRNA-4157/V940 and pembrolizumab improves recurrence free survival (RFS) compared to pembrolizumab alone in participants with complete resection of cutaneous melanoma and a high risk of recurrence. mRNA-4157/V940 is designed to stimulate an immune response by generating a specific T cell action based on the unique mutational signature of a patient’s tumour.

In the trial, and following complete surgical resection, patients were randomised to receive mRNA-4157/V940 (nine total doses of mRNA-4157) and pembrolizumab 200 mg every three weeks up to 18 cycles (for approximately one year) or pembrolizumab alone. The primary endpoint of the trial was recurrence-free survival whereas secondary endpoints include distant metastasis-free survival and safety.

mRNA-4157/V940 preliminary efficacy data

The results are for 157 patients with stage III/IV melanoma. The data show adjuvant mRNA-4157/V940 and pembrolizumab reduced the risk of recurrence or death by 44% (hazard ratio, HR = 0.56, 95% CI 0.31 – 1.08, one-sided p = 0.0266) compared with pembrolizumab alone.

In terms of safety, serious treatment-related adverse events occurred in 14.4% of patients who received the combination treatment compared to 10% with pembrolizumab alone.

Stéphane Bancel, Moderna’s Chief Executive Officer, said: ‘Today’s results are highly encouraging for the field of cancer treatment. mRNA has been transformative for COVID-19, and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomised clinical trial in melanoma.’

The companies plan to discuss the results with regulatory authorities and initiate a Phase 3 study in melanoma patients in 2023.

Tumour-infiltrating lymphocyte therapy superior to ipilimumab in advanced melanoma

29th September 2022

Tumour-infiltrating lymphocyte therapy improved progression-free survival compared to ipilimumab in patients with advanced melanoma

Tumour-infiltrating lymphocyte therapy (TILT) provided superior progression-free survival to immune checkpoint inhibitor therapy with ipilimumab in a phase 3 trial of patients with advanced melanoma according to the findings of a study presented at the European Society for medical Oncology (ESMO) Congress by Dutch researchers.

Tumour-infiltrating lymphocyte therapy is a type of adoptive cellular therapy in which infiltrated lymphocytes are removed from a patient’s tumour and grown in large numbers in a laboratory. These cells are then infused back into the patient to help the immune system kill the cancer cells.

In fact, studies have already suggested that TILT can mediate a durable complete responses in patients with metastatic melanoma with similar efficacy irrespective of prior treatment. In a phase 2 open-label trial, Lifileucel, which is an autologous, centrally manufactured tumour-infiltrating lymphocyte product, demonstrated durable responses, addressing a major unmet need in patients with metastatic melanoma with limited treatment options after approved therapy.

However, to date, there have been no phase 3 trials examining the value of tumour-infiltrating lymphocyte therapy in patients with advanced melanoma.

The current study was a multicentre, open-label phase 3 trial of patients with unresectable stage IIIC-IV melanoma, aged between 18 and 75 and who were randomised 1:1 to TILT or ipilimumab (3mg/kg q3wks, max 4 doses). Individuals were stratified for BRAFV600 mutation status, treatment line and centre.

Those receiving TILT underwent resection of a melanoma lesion (2-3cm) for the ex vivo outgrowth and expansion of tumour resident T cells. The researchers set the primary endpoint as progression-free survival (PFS) per RECIST 1.1 whereas secondary endpoints were (overall and complete) response rate, overall survival (OS) and safety.

Tumour-infiltrating lymphocyte therapy and progression-free survival

A total of 168 patients, the majority (86%) of whom were refractory to anti-programmed cell death-1 ligand treatment, received TILT (84) or ipilimumab.

After a median follow-up of 33 months, the median PFS was 7.2 months for TILT (95% CI 4.2 – 13.1) compared to 3.1 months (95% CI 3.0 – 4.3) for ipilimumab, giving a hazard ratio, HR of 0.50 (95%CI 0.35 – 0.72, p < 0.001).

The overall response rate was 49% for TILT but only 21% for ipilimumab and 20% of those receiving TILT achieved a complete response compared to 7% for ipilimumab. The median OS for TILT was 25.8 months and 18.9 months for ipilimumab. Moreover, grade ≥3 treatment-related adverse events occurred in all TILT patients but only and 57% of those assigned to ipilimumab.

The authors concluded that TILT therapy significantly improved PFS compared to ipilimumab, adding that since the vast majority of those included in the trial were anti-PD-1 refractory, TILT was a potential new treatment option in this patient population.

Haanen JBAG et al. Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: Results from a multicenter, randomized phase III trial

Relatlimab-nivolumab combination effective in metastatic melanoma

21st January 2022

Relatlimab-nivolumab in combination led to an increase in progression-free survival in metastatic melanoma compared to nivolumab alone

The combination of relatlimab-nivolumab has been shown to improve progression-free survival to a greater extent that nivolumab alone in patients with metastatic or unresectable melanoma, compared to nivolumab alone. This was the conclusion of a Phase II-III trial by researchers from the Department of Melanoma Medical Oncology, University of Texas, US.

The prognosis for patients with advanced melanoma is poor, with 5-years survival rates of 5-19%, depending on the location and the number of metastases. Nevertheless, over the past decade, there have been improvements in survival for such patients, after the introduction of drugs such as ipilimumab (an anti–cytotoxic T-lymphocyte–associated antigen 4 monoclonal antibody) and anti–programmed death 1 agents such as nivolumab.

In fact, studies suggest that the combination of ipilimumab and nivolumab, can produce a median overall survival of more than 60.0 months, compared to 36.9 months with nivolumab and 19.9 months ipilimumab mono-therapy respectively.

Lymphocyte Activation Gene – 3 (LAG-3) is an immune checkpoint molecule that regulates both T-cell activation and homeostasis and is up-regulated in melanoma. In addition, it has been found that both LAG-3 and programmed cell death 1 (PD-1) act synergistically to regulate T-cell function to promote tumour immune escape.

Consequently, the use of relatlimab (an antibody that binds to LAG-3) and nivolumab (a PD-1 inhibitor), has showed promising anti-tumour activity, including a durable objective responses in patients with melanoma that relapsed after, or was found to be refractory to PD-1 inhibition.

For the present study, the US team used relatlimab-nivolumab as a fixed-dose combination, compared to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. They included patients 12 years of age and older, with previously untreated, histologically confirmed, unresectable stage III or IV melanoma.

In phase 2–3, double-blind trial, included patients were randomised 1:1 to 160 mg of relatlimab and 480 mg of nivolumab or 480 mg of nivolumab, with both therapies administered in a single 60-minute intravenous infusion every 4 weeks. The primary end point of the study was progression-free survival assessed according to RECIST, version 1.1.


A total of 714 patients with a mean age of 63 years (41.7% female) were randomised to either relatlimab-nivolumab (355) or nivolumab alone.

The median progression-free survival interval was 10.1 months with relatlimab–nivolumab and 4.6 months with nivolumab, giving a hazard ratio (HR) for progression or death of 0.75 (95% CI 0.62 – 0.92, p = 0.006). After 12 months, progression-free survival was 47.7% with relatlimab–nivolumab and 36% with nivolumab.

The authors concluded that their data support the role of dual checkpoint inhibition over mono-therapy and establish relatlimab–nivolumab as a potential new treatment option for patients with previously untreated metastatic or unresectable melanoma.


Tawbi HA et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. New Eng J Med 2022