Advanced melanoma trial when Keytruda alone is not enough

Published: Dec. 19, 2018 at 8:17 PM EST
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Keytruda can be an effective immunotherapy for advanced melanoma, but fewer than half of patients respond to it.

Now, a new combination therapy may be the accelerator researchers hoped to find.

Patients with metastatic melanoma have faced grim prospects: the American Cancer Society says the five-year survival rate is only 15 percent.

That started changing when the Food and Drug Administration approved Keytruda in 2014. Despite the drug’s success, 60 percent of patients didn’t respond.

Now, researchers at UCLA hope that adding a second drug could cut that number in half.

When John Gilligan was diagnosed with metastatic melanoma, he, his wife, Carol Baker, and his doctors chose the SD 101 clinical trial as a first-line treatment.

“The numbers for survival for metastatic melanoma have not been very good, so trying something experimental seemed like a good idea,” John said.

The trial combines the immunotherapy drug Keytruda with injections of SD 101 into tumors. SD 101 is a bacterialike agent that changes the microenvironment so the immune system kills cancer cells more effectively.

Oncologist Dr. Deborah Wong said it’s like a flare to get the process going.

“Not only does this combination work to shrink the tumor that we’re injecting, but on scans, the tumors apart, far away from the ones we’re injecting, also shrank,” Wong said.

Nine study participants got immunotherapy for the first time. Seven of them had good responses, including two whose tumors disappeared. That’s a 78 percent response rate, nearly twice as good as Keytruda alone.

The other 13 had had immunotherapy before and had modest or no response. After six months, John’s tumors disappeared. He now gets just Keytruda, with few side effects.

“I’ve managed to keep working and keep working out and being active and, you know, all of those things that help keep you optimistic,” he said.

He's optimistic enough to start planning a family trip to Paris when he retires next year.

The combination therapy does have some side effects, including flulike symptoms, injection site irritation and the possibility of toxic immune responses. John said most of his side effects went away when he switched to just Keytruda.

This trial was small, just 22 participants so far. UCLA’s Jonsson Comprehensive Cancer Center is now part of a 45-center trial testing SD 101 and Keytruda in patients with melanoma and neck cancer.




REPORT: MB #4514

BACKGROUND: Melanoma is not the most common skin cancer, but can be the most serious because it oftentimes spreads. Incidences of melanoma are increasing for people under the age of 40 years old, particularly women. Avoiding sunburn and overexposure to the sun are effective ways to reduce risk of skin cancer. Self-monitoring moles and other markings can help with early detection. Melanomas can develop anywhere on the skin, but certain areas such as the chest, back, legs, neck, and face are more prone than others. Melanoma is diagnosed in five stages, ranging from stage 0 (only in the outermost layer of the skin) to stage 4 (cancer has spread to distant lymph nodes or organs, such as the brain or lungs). The four types of melanoma are superficial spreading, nodular, lentigo maligna, and acral lentiginous. Research is ongoing into the causes for melanoma, but people with certain types of skin are more prone to developing it and factors such as a high number of moles, pale skin that does not tan easily, or red/light-colored hair may all increase incidence of skin cancer.


KEYTRUDA: Pembrolizumab or Keytruda is an immunotherapy medication that helps shrink tumors, helping patients with advanced staged melanoma live longer. It is an anti-PD-1 inhibitor, also known as a checkpoint inhibitor, helping make cancer cells more vulnerable to attack by using your body’s own immune system. It is an antibody that promotes the tumor-killing effects of T-cells; the white blood cells you have that help fight off diseases. In 2014 the FDA approved pembrolizumab to treat patients with the following advanced stages of melanoma: stage 3 that is unresectable or unable to be removed completely using surgery alone, and stage 4 also known as metastatic; meaning it has spread to other organs and parts of the body. Many experts recommend anti-PD-1 therapy as a first-line of treatment for patients with advanced melanoma, but you must speak with your physician about the risks and benefits.


COMBINATION APPROACH: In a UCLA-led study, a new combination treatment option is proving more effective for patients receiving immunotherapy for the first time. Using the immunotherapy drug pembrolizumab and the experimental agent SD-101, which is comprised of a sequence of nucleic acids, it mimics an infection, which alters the environment around the tumor in such a way that enables the immune system to more effectively attack the cancer. The research was part of an early-stage study, and conducted to test the best dosage of the potential new combination therapy as well as its side effects. Their findings were published in the journal Cancer Discovery. Researchers found the reason patients did not initially respond to the Keytruda immunotherapy is their immune system was not ready. Injecting the therapy drug SD-101 could change the environment of the cancer and prepare the system to better respond to the Keytruda.