Combination Therapy May Offer Alternative Treatment Option for Advanced Melanoma


Combining pembrolizumab (Keytruda) and an investigational drug could benefit patients with advanced melanoma who have not responded to immunotherapy treatment.

A new combination therapy approach may improve immunotherapy treatment for patients with advanced melanoma, according to a study recently-published in Cancer Discovery.

The study showed that combining the immunotherapy pembrolizumab (Keytruda) with an experimental, bacteria-like agent called SD-101, enabled the immune system to more effectively attack the cancer.

Although immunotherapies have advanced cancer treatment, only a subset of patients respond to the therapy, highlighting the need to better enhance the use of these therapies.

Using a newly-identified combination regimen, University of California, Los Angeles (UCLA) researchers conducted an early-stage study to evaluate the adverse effects and best dosage of the potential new therapy.

“We have found that the reason patients with metastatic melanoma do no initially respond to immunotherapy with an anti-PD1 is that their immune system was not ready,” lead study author Antoni Ribas, professor of medicine at the David Geffen School of Medicine at UCLA and director of UCLA Jonsson Comprehensive Cancer Center Tumor Immunology Program, said in a press release. “So we thought, ‘What if we change that by injecting the therapy drug into the metastatic legions and change the microenvironment of the cancer?’”

By making the microenvironment more hospitable for T cells, SD-101 can better destroy the cancer cells, the researchers noted.

The study included 22 patients who had an advanced stage of inoperable or metastatic melanoma.

Nine of these patients were receiving treatment with an immunotherapy for the first time, according to the study. Among these 9 patients, the overall response rate (ORR) was 78%, the estimated 12-month progression-free survival (PFS) rate was 88%, and overall survival (OS) rate was 89%. Of the 13 patients who had previously received a type of immunotherapy, the ORR was 15%.

The most common adverse events related to SD-101 were injection site reactions and mild-to-moderate flu-like symptoms, according to the study.

The findings suggest that the combination of pembrolizumab and SD-101 could potentially be used as an alternative treatment for patients with melanoma whose tumors have not responded or would be unlikely to respond to other therapies.

According to the researchers, gaining insight into how these immunotherapies work in patients is crucial to developing more effective approaches to treating these cancers.

“By understanding that, we can find more ways to make that therapy more active. One way is by combining the therapy with another agent that can overcome the resistance that some cancers have to these therapies,” Dr Ribas concluded.


Ribas A, Medina T, Kummar S, et al. SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase 1b, multicenter study. Cancer Discovery. 2018. Doi: 10.1158/2159-8290.CD-18-0280.

Combination approach shows promise for beating advanced melanoma [news release]. UCLA Jonsson Comprehensive Cancer Center’s website. Accessed August 28, 2018.

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