Maximizing the Potential of Immunotherapy the Focus of Cancer Moonshot 2020

December 2016, Vol 7, No 11

Washington, DC—The Cancer Moonshot 2020 program is exploring a new paradigm in cancer care by bringing clinical trials focused on immunotherapy to community and academic practices. This privately funded initiative seeks to conduct phase 2 clinical trials within the next 36 months in 20,000 patients with >20 tumor types at all stages of cancer, said Gary Palmer, MD, JD, MPH, Chief Medical Officer, President, GPS Operations, NantHealth, Culver City, CA, at the Sixth Annual Conference of the Association for Value-Based Cancer Care.

Dr Palmer discussed the novel treatment approaches that are being explored in conjunction with immunotherapy.

Cancer turns off the immune system, a finding that has led to the use of checkpoint inhibitors to take the brakes off the immune system in cancer.

“The onset of immunotherapy is one of the real keys to the bright future of oncology,” said Dr Palmer.

Because of resistance mechanisms and tumor heterogeneity, “we’re hitting a wall with single-agent targeted therapies,” he said. Impressive responses occur with single-agent targeted therapy, but these responses are often short-lived.

The recurrence of cancer after initial success with therapy that is targeted to a driver mutation is, in part, attributed to the emergence of multiple cancer subclones during cancer progression. Dr Palmer presented findings from a study involving NantHealth members with triple-negative breast cancer who had multiple tumor biopsies at one time point, and multiple biopsies at different time points.

The genomic profiles of each of the 3 tumor biopsies performed at the same time point were not identical. In addition, the genomic profiles differed over time as the cancer was treated. The heterogeneity in the genomic profiles makes selection of therapy challenging.

The exact genomic profile of tumors may not matter if the immune system recognizes all tumors as foreign, said Dr Palmer. With immunotherapy, “we can harness that immune system to attack all of the different metastatic sites at one time point, and all of the different changes over different time points,” he said. “That’s being a little simplistic, but if you start thinking that way, you can see how immune therapy may get over some of the issues of heterogeneity and genomic changes.”

Dr Palmer said that the ultimate goal is not to eliminate targeted therapies, but to add immunotherapies and immune enhancers that can make the responses more durable.

Cancer Moonshot 2020

The Cancer Moonshot program is a coalition of healthcare stakeholders united by the goal of accelerating the use of immunotherapy in patients with cancer.

The program brings together pharmaceutical companies, academic centers, community practices, and manufacturers of cancer-fighting agents (eg, vaccines, nanoparticle chemotherapy, and natural killer cells). The rationale is that by combining immunotherapy modulators in a rational order, the potential of immunotherapy in controlling cancer can be maximized.

The goal of the program is to evaluate 100,000 patients with >20 tumor types and to enroll 20,000 of these patients into immunotherapy-based clinical trials.

“Those of you in research know that a 20% enrollment rate is extremely high. This is a lofty goal, but there’s a lot of money,” said Dr Palmer. “One of the thoughts is to put patients on trials early on, obviously where there aren’t curative or very effective therapies, and use low-dose chemotherapy,” he said.

“We know that low dose chemotherapy, for example, is an immune stimulator. It induces a stress reaction to the cancer cell and makes the cancer cell more visible to the innate immune system, plus it may have some benefits in killing some cancer cells,” added Dr Palmer. Low-dose radiation therapy will also be assessed as a treatment regimen.

Natural killer cells are lymphocytes that exert cytotoxic activity on recognition of foreign cells. Natural killer cells can be genetically modified to produce cytokines that enhance their antitumor effect. In addition, low-dose chemotherapy can manipulate T-cells and suppressor T-cells to increase immune system activity.

Advances in cancer vaccines are being realized as a result of advances in adenoviral vectors in establishing the identity of neoepitopes, Dr Palmer said. Neoepitopes are the proteins on the surface of the cancer cell that give it a unique identity.

One of the challenges lies in discovering the optimal sequence for various therapies. “One thing that’s pretty clear is the vaccine would probably be given later, since the neoepitope determination has to be made first, and then the vaccine is developed specifically for that particular patient. This, in essence, is what the Cancer Moonshot program entails,” he said.

The GPS Cancer Test

Maximizing the benefits of treatment requires knowledge of a cancer’s molecular profile to better inform treatment. As a key enabler for the Cancer Moonshot program, NantHealth’s GPS Cancer test integrates whole-genome sequencing, whole-transcriptome sequencing, and quantitative proteomics to provide a comprehensive molecular profile of a cancer to inform personalization of treatment strategies.

“This test gives you what we call battlefield awareness…a little bit of the picture of what the genomics and proteomics of the tumor look like that help to define the immune therapy going forward,” Dr Palmer said.

One way the test may enhance value in the treatment of cancer is by enabling the use of lower-cost chemotherapy, with knowledge of quantitative proteomic chemoresistance or chemosensitive biomarkers before treatment begins, he said.

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