ASCO20 Update: Cellular Immunotherapies, Genomics, and COVID-19

“When I chose the  annual meeting theme ‘Unite and Conquer: Accelerating Progress Together’ early last year, I never imagined it would take on new meaning twelve months later,” declared American Society of Clinical Oncology (ASCO) president Howard Burris III, MD, during his opening address at ASCO’s 56^th annual meeting.

“While normally we would be together in the great halls of Chicago’s McCormick Place, this year the convention center is a living symbol of uniting to conquer,” Now, the place where ASCO20 was supposed to take place has been transformed into a massive tent city for patients with COVID-19.

“We may not be in the same room for this year’s meeting, but [the medical and scientific community] is more united than ever.” Indeed, in addition to frontline physicians and nurses pitching in to fight the novel SARS-CoV-2 coronavirus pandemic however they can, scientific researchers are also contributing. This includes a number of CRI scientists, who have lent their expertise in cancer immunology to efforts against the pandemic.

The commitment of all those involved in combatting COVID-19, Burris said, “mirrors our consistent, ongoing, and unwavering dedication to saving the lives of our patients with cancer,” and ASCO20 remained focused first and foremost on highlighting the advances made against cancer. Many of these involved immunotherapy, especially cellular immunotherapies.

CELLULAR IMMUNOTHERAPY ADVANCES AT ASCO20

CAR T cell therapy targeting the CD19 marker has already made an impact in B cell blood cancers, particularly leukemia and lymphoma. As noted by Suzanne Lentzsch, PhD, a CRI CLIP Investigator at Columbia University Medical Center, there was a 45 percent decrease in stem cell transplants among lymphoma patients with diffuse large B cell lymphoma in 2018 compared to 2017, which she suggested was likely due to the FDA approval of the first CAR T cell immunotherapy for lymphoma in 2017.

Encouraging results with CAR T cells were also seen in multiple myeloma. In the phase 1 KarMMa trial discussed by Nikhil C. Munshi, MD, of the Dana Farber Cancer Institute, patients with relapsed multiple myeloma were treated with idecabtagene vicleucel, a CAR T cell therapy that targets the BCMA marker found on these cells. This led to frequent, deep, and durable responses in heavily pre-treated patients, especially with the highest dose. Additionally, only 6 percent of patients experienced serious side effects (grade 3 or higher).

The potential of an off-the-shelf CAR T cell therapy was presented by Sattva S. Neelapu, MD, of the University of Texas MD Anderson Cancer Center. In the phase 1 ALPHA clinical trial, patients with relapsed or refractory non-Hodgkin lymphoma were treated with ALLO-501, a CD19-targeting CAR T cell therapy. This approach could get to patients more quickly and less expensively than currently approved CAR T therapies that are made individually for each patient. The natural T cell receptor (TCR) was removed from the CAR T cells to prevent them from attacking the patient’s normal tissues. They were also modified to have their CD52 receptors removed, so that an anti-CD52 treatment could be administered to prevent the patient’s immune system from attacking the engineered CAR T cells. Overall, twelve of nineteen patients (63 percent) responded. Of the eight who received the highest dose, half had complete responses.

Excitingly, two other adoptive cell therapies involving T cells showed promise in solid cancers, although only in small numbers of patients.

Engineered T cell receptor (TCR) T cells targeting an HPV-associated marker—the E7 protein—were effective in patients with metastatic and refractory cancers associated with HPV16, including cervical and head and neck cancers, according to Christian S. Hinrichs, MD, of the National Cancer Institute. Hinrichs presented results from a phase 1 trial in which half the twelve patients treated responded, including four who did not respond to prior PD-1 immunotherapy. Most patients also had at least one of their tumors completely eliminated, and responses were associated with expansion of the supplied T cells.

David S. Hong MD, of MD Anderson Cancer Center, spoke about another engineered TCR therapy—ADP-A2M4 SPEAR T cells—that targets the cancer-testis antigen MAGE-A4. In a phase 1 trial involving patients with diverse types of MAGE-A4-positive cancers, 9 of 38 patients responded. Seven of fifteen (47 percent) of synovial sarcoma patients responded, and fourteen of fifteen (93 percent) experienced disease stabilization.

CHECKPOINT IMMUNOTHERAPY FOR RARE AND UNKNOWN CANCERS

Roughly 2 to 5 percent of cancers are of unknown primary origin (CUP), which can limit doctors’ ability to prescribe the best treatment for their patients. Junko Tanizaki, MD, PhD, of Kindai University in Japan discussed whether immunotherapy—in particular PD-1 checkpoint inhibition—might be a sensible option for some of these patients. She focused on the phase 2 NivoCUP trial, in which nivolumab (Opdivo®) led to responses in 10 of 45 patients with CUP that had been previously treated, and in two of eleven patients who hadn’t received prior treatment.

To tailor care even further for these and other rare types of cancer, genomic testing might be able to help doctors better treat these as well as other types of rare cancers by matching patients to certain treatments based on the mutations their tumors have. As demonstrated by Shumei Kato, MD, of the University of California, San Diego, this can be acquired by analyzing cell-free DNA from patients’ blood, and is particularly relevant for checkpoint inhibitor immunotherapies targeting the PD-1/PD-L1 pathway, which have been shown to be remarkably effective against heavily mutated cancers associated with defects in DNA repair and microsatellite instability (MSI-high). Moving forward, this approach could harmonize with more precise immune-based approaches, including vaccines, antibodies, and cell therapies that target specific antigens.

COVID-19 AND CANCER

Norman E. Sharpless, MD, the director of the National Cancer Institute (NCI), led the final Saturday session at ASCO20, which focused on how COVID-19 has impacted clinical cancer care.

Sharpless focused on the challenges the NCI has faced when it comes to maintaining cancer care through this crisis and how it’s responded. Specific issues Sharpless mentioned included:

• delayed diagnoses
• decreased screening
• reduced or non-standard care
• reduced clinical trials and drug discovery activities
• increased cost of clinical trials
• slowing of basic cancer research due to lab closures.

To adapt, the NCI has sought to provide their grantees with flexibility through measures such as deadline and eligibility extensions, and enabling funds to be carried over. Additionally, the NCI is helping the U.S. Food and Drug Administration (FDA) evaluate commercially available blood tests for COVID-19 and is working to make high-quality tests available nationwide.

Regarding clinical trials, the NCI is is allowing changes to trial protocols, and is spearheading a trial that seeks to enroll at least 2,000 cancer patients with COVID-19, at more than 1,000 sites. Eligible patients must be currently receiving cancer therapy or going through routine followup blood work. Emphasis was placed on recruiting at-risk patients from minority, underserved, and rural populations. Sharpless noted that this trial took only six weeks to launch after the idea was conceived, an extremely rapid turnaround compared to the year or more a trial would normally take to initiate.

Following Sharpless was Jeremy L. Warner, MD, of Vanderbilt University, who spoke about the recently formed COVID-19 and Cancer Consortium (CCC19), which is collecting and compiling data from 106 different institutions around the U.S. in order to disseminate this important information as widely and as rapidly as possible. So far, more than 1,000 patients have been included, and the investigators have observed several factors that appear to be associated with increased risk of death. These include being male, being older than age 75, and having a progressing cancer. He concluded by emphasizing that further clinical trials are needed to define the risks and benefits of various treatments for cancer patients also afflicted with COVID-19.

Follow us for our next update from #ASCO20, which will feature immunotherapy breakthroughs from the plenary and developmental therapeutics sessions as well as additional cancer-specific talks, including bladder cancer, lung cancer, and melanoma, among others.

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