Strong results halt melanoma trial of PD-1 drug

A phase 3 trial of Bristol-Myers Squibb’s nivolumab has been halted because of strong evidence of its effectiveness in treating advanced melanoma.

The news will only add to excitement around nivolumab, one of several new immunotherapy drugs in the PD-1 checkpoint inhibitor and PDL-1 classes – many expect these drugs to be a major step forward in treating a range of cancers.  The news is particularly significant as it is the first time any of the drugs has shown to improve survival in a late-stage trial.

The halted trial was evaluating nivolumab versus dacarbazine (DTIC) in patients with previously untreated BRAF wild-type advanced melanoma, and was stopped early after analysis by the Data Monitoring Committee (DMC) showed evidence of superior overall survival in patients receiving nivolumab compared to the control arm. Patients in the trial will now be unblinded and allowed to cross over to nivolumab.

“The outcome of CheckMate -066 is an important milestone in the field of immuno-oncology as it represents the first well-controlled, randomised Phase 3 trial of an investigational PD-1 checkpoint inhibitor to demonstrate an overall survival benefit,” said Michael Giordano, MD, Head of Oncology Development.

“Bristol-Myers Squibb is committed to continuing to lead advances in immuno-oncology and to executing our strategy to provide patients with the best opportunity to achieve the potential for long term survival.”

The study, which was designed in consultation with the Committee for Medicinal Products for Human Use (CHMP), was primarily conducted in countries where DTIC is a commonly-used treatment in the first-line setting, including Canada, but not at US trial sites. The Company will complete a full evaluation of the final CheckMate -066 data and work with investigators on the future presentation and publication of the results.

Analysts say that the halting of this trial could mean another phase 3 study, Checkmate 037, could also be stopped early. This trial – in which nivolumab is being compared to chemotherapy following failure of Yervoy – is the key one for FDA approval, and would otherwise run until May next year.

First approval approaching

Nivolumab is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. The principle is that nivolumab and other drugs with a similar mechanism can help the immune system to recognise and then attack and destroy cancer cells.

BMS is in a race with a number of other companies to be the first to have one of the new immunotherapies on the market. Merck’s MK-3475 and AstraZeneca’s AZD9291 have all shown promising results across a range of hard to treat cancers.

Merck’s MK-3475 looks set to win the race, with the FDA set to pass judgement on it on 28 October for use in melanoma patients.

Like its rivals, Bristol-Myers Squibb has responded to the promise of its immunotherapy by rapidly expanding its trial programme. The firm has is studying nivolumab in multiple tumour types across 35 trials – as monotherapy or in combination with other therapies – in which more than 7,000 patients have been enrolled worldwide. Among these are several potentially registration trials in non-small cell lung cancer, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma.

In 2013, the FDA granted Fast Track designation for nivolumab in NSCLC, melanoma and RCC. Then in May this year the US regulator also gave it Breakthrough status for patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab.



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