Immunotherapy Combo Appears Safe, Shrinks Metastatic Melanoma Tumors

Researchers conducting a first-of-its-kind study combining the checkpoint inhibitor tremelimumab with an anti-CD40 monoclonal antibody drug report the dual treatments are safe and produce a clinical response in metastatic melanoma patients.

Researchers presented the abstract for the Phase I trial April 19 during the American Association for Cancer Research (AACR) Annual Meeting 2015 in Philadelphia.

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“… new treatment protocols combining immunotherapies are coming. This is the first combination of an immunostimulatory agent with checkpoint blockade,” said lead author David Bajor, M.D., instructor in the division Hematology/Oncology in the Perelman School of Medicine, University of Pennsylvania. “When they are thoughtfully combined with immune-stimulating compounds like CD40 or drugs targeting other facets of the immune system, we hope to be able to increase the response rate to previously approved therapies.”

Researchers enrolled 24 metastatic melanoma patients who had not been treated with either drug nor any cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor. Patients received doses of tremelimumab every 12 weeks and doses of anti-CD40 every three weeks, and researchers evaluated the patients every three months.

NEXT: Results after a median 22-month follow-up

After a median 22-month follow-up, they found that the drugs were safe and shrank tumors in a subset of patients, with an overall response rate of 27%. Two patients had complete responses and four had partial responses. Among those responding were patients with highly morbid, visceral disease, according to Dr. Bajor.

The median progression-free survival was 2.5 months and the median overall survival was 26.1 months, according to a Penn Medicine press release.

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And while researchers were concerned that the combination could increase side effects, that didn’t happen in this study.

“Generally, the adverse event profile seen in this particular combination (agonistic CD40 and tremelimumab) is similar to that of each drug alone,” Dr. Bajor said. “The most significant dermatologic toxicity we saw was pruritus. Notably, several of our patients who did very well and, thus, were on the combination for many months had grade 2 pruritus with or without a macular/papular rash. Identifying non-corticosteroid based treatments for this side effect could greatly improve the comfort and quality of life for patients receiving this type of treatment, while allaying the oncologists’ fears of dampening the immune response.”

Dr. Bajor has no relevant disclosures.

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