The Asco Post

ASCO 2013: Phase I Trial Suggests Ipilimumab and PD-1 Drug Nivolumab May Be Better Together than Alone for Advanced Melanoma

By The ASCO Post
Posted: 5/17/2013 11:46:50 AM
Last Updated: 5/17/2013 11:46:50 AM

Key Points:
  • In a phase I trial, patients with inoperable stage III or IV melanoma who had undergone up to three prior therapies received combination therapy with ipilimumab and nivolumab.
  • In the three completed treatment arms, tumor shrinkage rates were 21%, 53%, and 50%, with highest rates seen in patients treated with the highest dose of both drugs.
  • While the data are still preliminary, it appears that even patients who initially had little benefit from ipilimumab had significant tumor shrinkage after subsequent treatment with nivolumab.

Results from a phase I study show that combination therapy with ipilimumab (Yervoy) and the investigational antibody drug nivolumab led to lasting tumor shrinkage in approximately half of patients with aggressive, advanced melanoma. The results will be presented at the 2013 ASCO Annual Meeting in Chicago (Abstract 9012).

Ipilimumab is a standard treatment option for advanced melanoma in many countries. Nivolumab, used alone, has shown promising activity against melanoma and other cancers. Both nivolumab and ipilimumab are antibody drugs that target immune system “gatekeepers” or checkpoints (PD-1 and CTLA-4, respectively) on immune cells, effectively releasing the brakes on the immune system and boosting its ability to fight off cancer. This proof-of-principal study shows that concurrent use of two immune checkpoint antibodies offers a promising strategy for advanced melanoma therapy.

“The complete and near-complete response rates we’re seeing are unprecedented for an immunotherapy in melanoma. We were particularly impressed that the drugs work together so well,” said Jedd D. Wolchok, MD, PhD, a medical oncologist at the Memorial Sloan-Kettering Cancer Center. “Melanoma researchers have been hopeful that combination regimens would increase the effectiveness of single-agent immunotherapies, and now we have confirmation that such an approach has significant potential.”

Phase I Trial

In this trial, patients with inoperable stage III and stage IV (metastatic) melanoma who had undergone up to three prior therapies were assigned to six different treatment arms. The current results are based on 52 patients in three completed treatment arms, in which patients received concurrent treatment with the two drugs.

In those three arms, tumor shrinkage rates were 21%, 53%, and 50%, with highest rates seen in patients treated with the highest dose of both drugs. The responses to therapy were rapid for an immunotherapy: Three out of four patients who responded to the concurrent treatment experienced tumor reduction within the first 3 months, which is faster than with single-agent ipilimumab. Thirty-one percent of patients (16 out of 52) experienced significant tumor shrinkage of more than 80%.

Two of the remaining three arms enrolled patients who had undergone prior ipilimumab treatment. Those patients received only nivolumab on this study. While the data are still preliminary, it appears that even patients who initially had little benefit from ipilimumab had significant tumor shrinkage after subsequent treatment with nivolumab.

Side effects have been manageable in the trial and did not impact the positive therapeutic activity for the majority of the patients in this analysis. A randomized phase III trial of the nivolumab/ipilimumab combination as first-line therapy for patients with advanced melanoma is scheduled to begin in June 2013.

‘A Tremendous Advance’

Commenting on the study, ASCO President Sandra M. Swain, MD, FACP, said, “The further exploration of immunotherapy as stand-alone therapy without chemotherapy for a devastating disease such as advanced melanoma is a tremendous advance. We are identifying therapies that appear better together than alone, and look promising for more than just a small subset of patients. The extensive tumor shrinkage that was observed in this study is exactly the type of benefit patients and doctors have been hoping for.”

This research was supported by Bristol-Myers Squibb.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.

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