Previously underserved patient populations could soon benefit from new therapy approaches.

ASCO 2022 with its 31,000 live and 11,000 virtual attendees produced some excitement — not the least of which was the ability to network face to face on the latest advancements in cancer care. Of the nearly 3,000 abstracts presented, several were notable and potentially practice changing, not years down the road, but in the very near future. The most exciting discoveries are those redefining approaches to certain cancers in ways that will represent a paradigm shift in treatment approaches as well as the way patients’ disease is currently classified.


Newly defined group of breast cancer patients

The most lauded presentation was the Destiny-04-Breast study — a first-of-its-kind randomized Phase III study of a HER2-directed therapy in patients with HER2-low Metastatic Breast Cancer (mBC). This study evaluated Trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy in patients with HER2-low mBC, demonstrating a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or mBC regardless of hormone receptor (HR) status versus physician’s choice of chemotherapy.

Destiny-04 has literally defined a new group of breast cancer patients who previously had few treatment options because their cancer lacked a certain characteristic. About 20% of mBCs are considered HER2-positive, and drugs that target these cancers have dramatically improved patient survival rates.

ASCO 2022: Key Takeaways

  • HER2 therapies show efficacy in breast cancer patients with low levels of HER2 expression.
  • mRNA technology reaches a new milestone with encouraging results in pancreatic cancer treatment.
  • Colorectal patients in small study have complete remission.
  • CAR-T cell therapies show competitive efficacy with improved manufacturing scalability.

That leaves 80% of mBC patients with fewer treatment options. However, research has shown that 55%-60% of these actually express low levels of HER2, and this is the category that Destiny-04 targeted, demonstrating that the legacy cutoff point to determine HER2 positivity can now be extended. These results establish HER2-low metastatic breast cancer as a targetable population of breast cancer, with T-DXd as a new standard of care in this setting. This effectively means that approximately 50% more patients are now candidates for a potentially life-saving treatment.


mRNA technology proves viable for pancreatic cancer patients
Prior to the COVID-19 pandemic, mRNA technology to treat disease had been in research for several decades — and always under a cloud of doubt. But the pandemic put this technology on the fast track for development when the vaccines proved successful. As has so often happened in science, a crisis forced rapid advancement. Now, mRNA is being investigated in many therapeutic areas, including multiple types of cancers.

A Phase I study on a personalized vaccine for pancreatic ductal adenocarcinoma (PDAC) stood out at ASCO. For sixteen patients who had undergone surgery, tumors were sent to a lab in Germany where they underwent pathologic review and genomic analysis within 72 hours. This “real-time” manufacturing meant it was able to create a personalized vaccine very quickly. Each individual vaccine was encoded to give the highest likelihood to help that particular person’s immune system recognize the cancer. This differs from the COVID vaccine which is the same for every person.

Advances in pancreatic cancer are critical, as traditional chemo and immuno therapies are mostly ineffective against this cancer, and 90% of patients diagnosed die within two years. This promising early study showed that half of the patients remained cancer-free 18 months after having their tumors surgically removed and taking the mRNA vaccine. Far from the traditional approaches, this concept of creating a personalized vaccine that can enlist the immune system to fight pancreatic cancer may seem futuristic, but this study has shown that it is distinctly possible. The team is moving forward with larger, randomized studies with the hope that this treatment might be a near-future game changer for this underserved patient population.


Groundbreaking study for colorectal cancer
Another study result that made headlines around the world was reported in a late-breaking presentation on locally advanced colorectal cancer. In a single institution Phase II study of dostarlimab for patients with mismatch repair deficient (MMR) colorectal cancer with locally advanced disease, rectal cancer disappeared entirely for all 14 patients in the study. The promise of this study is the possibility that immunotherapy can replace surgery, chemotherapy and radiation, which are currently the standard treatments and can have debilitating health effects. Fertility, sexual health, bowel and bladder function are all negatively effected, and about 1/3 of treated patients end up with a colostomy.

It’s early yet, but the fact that any cancer trial ends in complete remission in 100% of patients is more than exciting. As Dr. Lee Schwartzberg, one of George Clinical’s scientific leaders in oncology, has said, “It’s a small group of patients. But it highlights this exquisite sensitivity when you know the target and you have a good drug against the target, and, in particular with immunotherapy, when you use it up front with an in-tact immune system. There are a lot of exciting learnings from this study.”


Improved manufacturing scalability of CAR-T cells
In CAR-T cell treatment, immune cells are harvested from a patient’s body, engineered in a lab to target tumors, and returned to the patient’s bloodstream. This represents the future of precision, personalized medicine. There are currently six available CAR-T therapies for the treatment of blood cancers. However, due to manufacturing and scalability issues, only a small percentage of potential patients have access to these treatments.

As of early 2021, over 500 CAR-T cell therapy clinical trials were being conducted worldwide, up from just over a hundred at the beginning of 2016. The ultimate goal is to make this very targeted form of treatment more widely available across disease states for many more patients — decreasing toxic side effects and increasing survivability. However, one problem with this form of therapy is the difficulty and expense in the processes involved.

Two presentations at ASCO 2022 showed manufacturing advances that could help get CAR-T therapy to more patients in the future. One Phase I study on multiple myeloma CAR-T therapy by Arcellx showed 100% of the 31 patients having at least some response, and 71% having a complete response to treatment. Although other studies have shown similar results, Arcellx has a manufacturing advantage with a proprietary binding technology, which could make the therapy more readily available in future.

Another Phase I study by Adicet Bio for a common form of lymphoma used donor-derived T-cells as the basis for treatment instead of patient-derived cells. They reported 75% of treated patients having a response with no serious side effects or dose-limiting toxicities. If donor-derived cells can be used in the future, it would mean that a scalable “off-the-shelf” manufacturing process is viable and that treatment would be accessible to many more patients around the globe.


Why we continue to do research
The above examples show that even the smallest of clinical trials can inform scientists of new and better ways to treat the diseases that burden populations globally. These are only a few examples that represent the best chance for a near-future paradigm shift in the way we diagnose and treat cancer. For all diseases, there is always something on the horizon that is just out of reach, if only we had one more piece of the puzzle. According to statistics, there were just over 400,000 registered clinical trials worldwide as of March, 2022, up from barely over 100,000 in 2010.

Research moves science forward and gives us the information needed to develop more individualized therapies with less side effects and more efficacy. Clinical trials are the gateway to the knowledge that can ease the global burden of disease and give patients worldwide a better chance at survival and a higher quality of life. Clinical researchers, investigators and the patients who volunteer for clinical trials are creating a lasting legacy for future generations.