Opdivo™ (nivolumab) shows superior progression-free survival in previously untreated advanced melanoma when given either alone or with Yervoy® (ipilimumab) versus Yervoy alone

• Opdivo+Yervoy regimen showed improved outcomes versus Opdivo monotherapy in PD-L1 non- and low-expressers (<5%)

MONTREAL, June 3, 2015 /CNW/ - New study results show that superior progression-free survival occurred in previously untreated patients with advanced melanoma when treated with a new Bristol-Myers Squibb immunotherapy, Opdivo™ (nivolumab), either alone or in combination with Yervoy^® (ipilimumab), compared to Yervoy alone, the current standard of care. The results of the phase 3 Checkpoint -067 trial were presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago and published in the New England Journal of Medicine.

Median progression-free survival (PFS), the co-primary endpoint, was 11.5 months for the Opdivo+Yervoy regimen (n-314) and 6.9 months for Opdivo monotherapy (n=316) versus 2.9 months for Yervoy monotherapy (n=315). The Opdivo+Yervoy regimen demonstrated a 58% reduction in the risk of disease progression vs. Yervoy (hazard ratio: 0.42; 99.5% CI, 0.31 to 0.57; P<0.0001), while Opdivo monotherapy demonstrated a 43% risk reduction versus Yervoy monotherapy (hazard ratio: 0.57; 99.5% CI, 0.43 to 0.76; P<0.00001). The hazard ratio for the exploratory endpoint comparing Opdivo+Yervoy PFS and Opdivo PFS was 0.74 (95% CI, 0.60 to 0.92).

Based on sub-analyses, the CheckMate -067 trial also allows for better understanding of the efficacy of the Opdivo+Yervoy regimen based on PD-L1 expression in patient tumours. In the trial, the Opdivo+Yervoy regimen demonstrated numerically longer PFS and a higher objective response rate (ORR) than Opdivo monotherapy in the overall population. Based on tumor PD-L1 expression, the greatest benefit of the regimen in PFS and ORR was seen in PD-L1 low- and non-expressing tumors. 

"These results are practice-changing, and provide new insights into the role that the PD-1 inhibitor nivolumab will play in the management of advanced melanoma," said Dr. David Hogg, of the Princess Margaret Hospital Melanoma Site Group in Toronto. "The data shows that nivolumab, on its own, or in combination with ipilimumab, a first generation immunotherapy, dramatically improves outcomes versus the standard single agent ipilimumab. I predict that the Checkmate-067 trial results will alter our future approach to metastatic melanoma patients, whose prognosis continues to improve." 

The safety profile of treatments was consistent with previously-reported studies evaluating the Opdivo+Yervoy regimen, and most treatment-related adverse events were resolved using established algorithms. The treatment-related adverse event rate was 95.5% for the Opdivo+Yervoy regimen compared to 82.1% for Opdivo monotherapy and 86.2% for Yervoy monotherapy. Most select treatment-related adverse events were resolved using established management guidelines. The trial is ongoing and patients continue to be followed for overall survival (OS), a co-primary endpoint.

The safety and efficacy of Opdivo for melanoma is still under investigation in Canada. Yervoy is approved in Canada for the treatment of unresectable or metastatic melanoma.

"Melanoma treatments have come such a long way. The past few years have been ground-breaking in terms of outcomes for this deadly cancer.  Not everyone responds to treatment in the same way and we want all patients to have the best possible chance. The only way for that to happen is for more treatment options to become available," said Annette Cyr, Chair of the Melanoma Network of Canada. "Ultimately what patients need and want is a chance to take on their cancer, a better quality of life and a chance at survivorship. The data that we are seeing at ASCO promise just that."

The safety and efficacy of Opdivo for advanced melanoma is still under investigation in Canada.

About CheckMate -067
CheckMate -067 is a Phase III, double-blind, randomized study that evaluated the Opdivo +Yervoy regimen or Opdivo monotherapy vs. Yervoy monotherapy in patients with previously untreated advanced melanoma. The trial enrolled 945 patients who were randomized to receive the Opdivo+Yervoy regimen (n=314), Opdivo monotherapy (n=316) or Yervoy monotherapy (n=315). Baseline disease characteristics, including BRAF mutation and PD-L1 status, were balanced across the 3 treatment groups.

Patients were treated until progression or unacceptable toxic effects. The minimum follow-up period after randomization was 9 months. Patients continue to be followed for overall survival (OS).

The co-primary endpoints were PFS and OS. Formal statistical analysis compared the combination regimen and Opdivo monotherapy to Yervoy. Exploratory analysis comparing the regimen to Opdivo was also conducted. In addition, exploratory analyses of PFS and ORR were conducted based upon PD-L1 expression. Exploratory endpoints include duration of objective response and safety/tolerability of study drug therapy.

The results comparing the Opdivo+Yervoy regimen to Yervoy monotherapy and Opdivo monotherapy to Yervoy monotherapy were consistently observed irrespective of BRAF status, PD-L1 expression, and metastasis stage.  

In addition, the Opdivo+Yervoy regimen and Opdivo monotherapy demonstrated higher ORR (57.6% and 43.7%, respectively) vs. Yervoy monotherapy (19%). The percentage of patients with a complete response was 11.5, 8.9 and 2.2, favoring the regimen over Opdivo monotherapy or Yervoy monotherapy. Time to objective response was similar in each group and the median duration of response was not reached in any of the groups.

Among patients with high PD-L1 expression (≥5%), ORR was 72.1% (95% CI, 59.9 to 82.3), 57.5% (95% CI, 45.9 to 68.5) and 21.3% (95% CI, 12.7 to 32.3) for the Opdivo+Yervoy regimen, Opdivo monotherapy and Yervoy monotherapy groups, respectively. In patients whose tumors expressed <5% PD-L1, the ORR was 54.8% (95% CI, 47.8 to 61.6), 41.3% (95% CI, 34.6 to 48.4) and 17.8% (95% CI, 12.8 to 23.8). Of note, comparable ORR was seen using the regimen in PD-L1 low- or non-expressing patients to those observed using Opdivo monotherapy in PD-L1-expressing patients. 

About Opdivo and Yervoy
Cancer cells may exploit "regulatory" pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo and Yervoy are both monoclonal antibodies and immune checkpoint inhibitors that target separate, distinct checkpoint pathways. Inhibition of these immune checkpoint pathways results in enhanced T-cell function greater than the effects of either antibody alone.

Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumor types consisting of more than 50 trials – as monotherapy or in combination with other therapies – in which more than 8,000 patients have been enrolled worldwide.

About advanced melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease, and occurs when cancer spreads beyond the surface of the skin to the other organs, such as the lymph nodes, lungs, brain or other areas of the body. An estimated 6,500 Canadians were diagnosed with melanoma in 2014ⁱ and 1,050 died from it.ⁱⁱ Melanoma accounts for 3% of all cancer diagnoses in Canada, making it one of the top 10 cancers diagnosed in Canada.ⁱⁱⁱ While melanoma accounts for 8% of all cases of skin cancer in Canada, it accounts for 70% of deaths from the disease.^iv The incidence of melanoma has been increasing in Canada. In the 25 years from 1986 to 2010, the incidence for men increased an average 2% per year from 9.0 to 14.7 cases per 100,000 and for women an average of 1.5% per year from 8.3 to 11.9 cases per 100,000, but the increase accelerated in the last 8 years to an average 2.9%.^v

Immuno-oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the mainstay of cancer treatment over the last several decades, but long-term survival and a positive quality of life have remained elusive for many patients with advanced disease. To address this unmet medical need, Bristol-Myers Squibb is leading research in an innovative field of cancer research and treatment known as immuno-oncology, which involves agents whose primary mechanism is to work directly with the body's immune system to fight cancer. The company is exploring a variety of compounds and immunotherapeutic approaches for patients with different types of cancer, including researching the potential of combining immuno-oncology agents that target different pathways in the treatment of cancer. Bristol-Myers Squibb is committed to advancing the science of immuno-oncology, with the goal of changing survival expectations and the way patients live with cancer.

About Bristol-Myers Squibb Canada
Bristol-Myers Squibb Canada is an indirect wholly-owned subsidiary of Bristol-Myers Squibb Company, a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb global operations, visit www.bms.com. Bristol-Myers Squibb Canada has been delivering innovative medicines for serious diseases to Canadian patients in the areas of cardiovascular health, oncology, neuroscience, immunoscience and virology for over 80 years. Bristol-Myers Squibb Canada employs over 300 people across the country. For more information, please visit www.bmscanada.ca.

Yervoy is a registered trademark of Bristol-Myers Squibb Company.
Opdivo is a trademark of Bristol-Myers Squibb Company.

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ⁱ Canadian Cancer Society, Canadian Cancer Statistics 2014, Chapter 7 Special Topic: Skin cancers, p. 77.
ⁱⁱ Canadian Cancer Society, Canadian Cancer Statistics 2014, Chapter 7 Special Topic: Skin cancers, p. 77.
ⁱⁱⁱ Canadian Cancer Society, Canadian Cancer Statistics 2014, Chapter 7 Special Topic: Skin cancers, p. 78.
^iv Canadian Cancer Society, Canadian Cancer Statistics 2014, Chapter 7 Special Topic: Skin cancers, p. 77 (6,500 melanoma cases of a total 82,600; 1,050 deaths of a total 1,490 in 2014).
^v Canadian Cancer Society, Canadian Cancer Statistics 2014, Chapter 7 Special Topic: Skin cancers, p. 79.

SOURCE Bristol-Myers Squibb Canada

Monica Flores, Public Affairs Lead, Bristol-Myers Squibb Canada, 514-333-3845, [email protected]; Jean Kanan, President and Principal Advisor, Spectrum Advisors, 514-234-4095, [email protected]