APOLLO immunotherapy clinical trial takes aim at cancer’s secrets

When Nancy Pinkston’s melanoma crept back, taking up residence in lymph nodes under her right arm, she and her oncologist in Dallas discussed her options.

Surgery is standard of care for her stage III melanoma. About 70% of patients who have surgery for that stage end up having a relapse.

“My oncologist knew about a clinical trial at MD Anderson that might be a good fit,” Nancy says. “She knew Dr. Hussein Tawbi and contacted him the day my scans came back.”

Within days, Nancy was in Houston meeting Tawbi and her surgeon, Jennifer Wargo, M.D. Nancy enrolled in a novel immunotherapy trial, which studies pre-surgical treatment with a drug that’s currently approved for stage IV metastatic melanoma.

The trial, co-led by Wargo and Rodabe Amaria, M.D., involves pre- and post-surgical treatment with a form of immunotherapy called immune checkpoint blockade, which frees the immune system to attack cancer, rather than attacking cancer directly.

Immunotherapy clinical trial yields no evidence of disease

For Nancy, surgery followed four rounds of treatment with nivolumab (Opdivo).

After her surgery in May, Nancy got the good news from Wargo: “All she found at surgery was dead tissue and the biopsy confirmed the good news – no evidence of disease.”

Clinical trial participants like Nancy are helping Wargo and her colleagues address a vital question: Why do these immunotherapy drugs work well for some patients, like Nancy, and briefly or not at all for others?

Biopsies before, during, after treatment

Nancy agreed to repeat biopsies during her melanoma treatment, beyond the usual pretreatment biopsy. Wargo is a leader of an effort to employ deep molecular and immune analysis of tumors before, during and after treatment to understand who benefits, who doesn’t and what to do next after any treatment fails.

“We should be incorporating this sort of biopsy and blood sample analysis into clinical trials, and ultimately we may even incorporate this into treatment with standard of care therapy. This effort is critical to guiding patient care in this era of precision medicine,” Wargo says.

Nancy’s clinical trial is part of MD Anderson’s Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform, one of our 10 Moon Shot™ platforms established to develop new treatment options for cancer patients. It’s designed to help us understand exactly how advanced cancers survive and help researchers understand which treatments will work best.

In the next two years, APOLLO is scheduled to conduct such analyses in 2,100 patients enrolled in 28 high-priority clinical trials for melanoma; multiple myeloma; glioblastoma; lymphoma; lung, breast, colorectal, pancreas and ovarian cancers; sarcoma; and cancers caused by the human papillomavirus.

A solid tumor pilot study using the APOLLO approach led by Wargo found analyzing biopsies taken early during treatment with a similar immunotherapy drug predicted which patients would respond. Before-treatment biopsies didn’t find predictive genomic or immune biomarkers.

Tumors evolve to survive

“Certainly, finding predictive biomarkers in pretreatment biopsies is the Holy Grail, but pretreatment and early on-treatment biopsies might be a winning combination,” says Andrew Futreal, Ph.D., co-leader of APOLLO and of MD Anderson’s Moon Shots Program™, which was designed in 2012 to save more lives by accelerating the development of new approaches based on scientific discoveries.

Wargo’s earlier study results, if confirmed by larger studies, could guide treatment.

“We could start by treating with an immunotherapy agent, do an early on-treatment biopsy and, based on that, either continue or add another agent,” Wargo says.

Cancer in its advanced stages survives by changing in response to treatment.

“If you don’t get a biopsy after treatment, you aren’t going to learn about how tumors evolve and resist treatment,” says Ignacio Wistuba, M.D., APOLLO co-leader and chair of Translational Molecular Pathology.

Repeat biopsies needed

A cancer patient generally undergoes a biopsy before starting treatment. After that, we typically track the tumor’s progression using CT or MRI scans for size and volume and PET scans for metabolic activity.

Futreal contrasts current biopsy practice to imaging: “We don’t take one CT scan initially and then use that same scan to assess how well treatment is working three months later. We take a new scan.”

Biopsies may be taken surgically, or via endoscopy or with radiologically guided core needles or fine needles that extract small samples from less accessible tumors.

Patients enrolled in clinical trials under the APOLLO protocol are asked to consent to repeat biopsies and multiple blood draws. They also may choose to refuse to have biopsies at any time during the study.

 “It’s been a really positive experience,” says Nancy, who completed her immunotherapy in late 2016, with no side effects from treatment. “Everyone at MD Anderson is so kind, helpful and compassionate.”

A longer version of this story originally appeared in Messenger, MD Anderson’s quarterly publication for employees, volunteers, retirees and their families.

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