I have a few more details about the Expanded Access Protocol for the combination of ipi and nivo.
The study has been approved by the FDA, which means it is posted on clinicaltrials.gov. This starts the process of getting sites open. The company is looking first to sites that have experience with the combination as part of the clinical trial process. It will take at least a month, and more likely six to eight weeks to start putting people on the drug, but everyone is working fast to shorten that time.
The study is open to people with Stage IV or unresectable Stage III melanoma, and it includes mucosal melanoma. It does not include ocular (uveal) melanoma because not enough patients with OM have been treated with the combination to know that it works in that population.
BRAF status doesn't matter, and prior treatment with a BRAF inhibitor is allowed. Prior treatment with ipi is not allowed.
Brain metastases must be stable for two weeks. This is actually great news, as the previous standard has been eight weeks.
Because ipi is an approved drug it must be provided as a prescription medicine and covered by insurance or some other program. Nivo will be provided free as part of the protocol.
So what does this mean? That is not entirely clear. Clinical trial data is based on a small group of patients, fewer than 100. Toxicities were high, with 2/3 of patients having Grade 3 or 4 toxicities. Toxicities, or side effects, are rated on a scale of 1 to 5, with 5 being death. Doctors involved in the study say that many of these higher grade toxicities were due to liver enzymes being out of normal range. The patients felt OK and the liver issues were dealt with fairly easily.
The results of this small study were very impressive. These patients were all in real trouble. They had experience as many as three prior systemic therapies and were now progressing again. Despite this, the dosage being used in the EAP had one and two year survival rates of 94 and 88 percent, respectively. Those numbers are very high.
Everyone in the field is watching this combination very carefully, with hopes that they strong results will hold up as the number of patients increase and as it is used in patients as their first therapy.