Gastrointestinal Cancers and Clinical Trials: What Patients Need to Know Earlier On

A Keck Medicine of USC gastrointestinal oncologist explains what patients need to know so they don’t miss the opportunity to participate in a clinical trial.

Breakthrough treatments for gastrointestinal cancers are being tested in clinical trials right now. For many patients, these trials are an invaluable opportunity to access novel therapies. Clinical trials offer cutting-edge opportunities for patients throughout their entire journey, including early in their disease course. This is why a consultation about potential trial options should occur before any treatment starts.

Before we get into clinical trials specifically, what are some of the most exciting advances happening in GI cancer treatment?

We are in an era of gastrointestinal oncology where treatment is not one-size-fits-all. Through molecular profiling, we’re able to study the profile of a patient’s tumor and determine which targeted therapy is going to enable the best outcome.

Here are a few examples: For esophagogastric cancers, in addition to chemotherapy we’ve now expanded our armamentarium to include agents that target PD-L1, HER2, deficiency of mismatch repair genes, CLDN 18.2 as well as other novel targets. The development of new immunotherapy agents, targeted antibodies as well as novel combinations of immunotherapy agents has allowed for new studies in patients with advanced or metastatic disease as well as patients with curable cancer. A new study evaluating the use of immunotherapy in patients in the perioperative setting before curative surgery has made immunotherapy plus chemotherapy a new standard of care for patients with cancer that is amenable to surgery.

How extensively is USC Norris Comprehensive Cancer Center involved in GI cancer clinical trials?

As part of the academic health system of Keck Medicine, USC Norris has a unique ability to offer patients a wide range of clinical trials. These trials range from phase 1 to phase 3 studies. A clinical trial can be a part of a patient’s journey at any point, from initial diagnosis to the point when standard-of-care treatments aren’t an option. These trials span many tumor types, including colorectal, gastric, esophageal, cholangiocarcinoma, pancreatic, liver and neuroendocrine tumors.

Our portfolio of clinical trials for gastrointestinal malignancies specifically includes more than 50 therapeutic trials. Our early-phase studies include 30 to 40 phase 1 studies assessing new drugs or new drug combinations, giving patients access to novel care. Our portfolio includes cutting-edge therapies such as cell engagers, which activate immune cells and bring them to the tumor; antibody-drug conjugates, which deliver chemotherapy in a more precise manner directly to the tumor; and new targeted therapies that go after genes previously thought to be “undruggable,” like RAS and p53. This extensive trial portfolio across gastrointestinal malignancies, novel agents and novel drug combinations can be relevant to a patient throughout their journey, from first-line and second-line treatment and beyond — and even in the setting where they may not have other treatment options.

Also, it’s important to know that although each of our GI oncologists may lead a particular clinical trial, all of our patients have access to any of our team’s studies.

You are the principal investigator on many GI cancer trials at USC Norris. Can you discuss some of them?

We have several first-line studies for patients with newly diagnosed disease. For example, we have a first-line study for patients with advanced gastric cancer or gastroesophageal (GE) junction cancer that looks at combining chemotherapy with the hematopoietic progenitor kinase 1 (HPK1) inhibitor, which has synergistic, immunostimulating properties added to standard-of-care immunotherapy and chemotherapy drugs.

Another is a first-line treatment available for the treatment of esophagogastric cancer, looking at the combination of chemotherapy, immunotherapy and the investigational drug pumitamig. Pumitamig is an antibody-drug conjugate (ADC) whose mechanism of action is both immunotherapeutic (PD-1) and targeting blood vessel formation in the cancer (VEGF). Pumitamig is a new class of drug called bispecific antibody targeting. In addition, we have other trials that are targeted to HER2 and CLDN 18.2.

What should patients and their providers know about clinical trial eligibility?

We want to make sure they know that many of these trials require that patients not have initiated treatment before being evaluated for a clinical trial. So, for instance, if a patient is newly diagnosed with GI cancer and has already started standard-of-care therapy with their local oncologist, they might not be eligible to participate in a clinical trial.

If patients think they might become interested in participating in a study, it’s important that they explore those avenues before starting standard-of-care treatment. If this does not happen, there are still opportunities for trials later in their journey, so a consultation to discuss trial options is appropriate at any time.

All candidates for clinical trials are first screened to determine if they meet certain criteria and are eligible to participate. This includes tumor profiling. It’s always helpful, but not necessary, if these tumor profiles have been done before patients see us. This way, we can identify appropriate studies efficiently. If a patient has already been referred to USC Norris, screening is done pretty quickly to determine if a patient may be eligible for a trial.

What if a patient is deemed ineligible?

We’re always happy to provide the patient with a second opinion and send them back to their referring provider for treatment, or we can continue to guide them through current treatment options here at USC Norris.

What are some common misconceptions patients have about clinical trials?

Some misconceptions may be that a patient enrolled in a clinical trial might not be receiving optimal treatment or might receive placebo drugs without any activity for their cancer. However, most clinical trials provide some level of therapy and usually, at minimum, standard-of-care treatment as an arm.

Some patients also wonder if clinical trials are safe, especially phase 1, 2 or 3 trials involving newer drugs. They should know that these trials — and especially phase 1 trials — involve very significant monitoring. If there is any indication that drugs are not going to be safe or are going to have increased side effects, adjustments are made immediately. Trial investigators meet on a weekly, if not biweekly, basis to review patient side effects and responses to treatment.

Finally, during a clinical trial, nothing is done without clear, informed consent from the patient. Both the patient and their clinician make educated, shared decisions together.

Why is it important for patients to consider participating in clinical trials?

It’s remarkable that currently only approximately 5% of patients who are diagnosed with cancer participate in clinical trials. Exploring clinical trials is such a good opportunity for patients and their physicians to learn about what treatments are out there and to potentially access new drugs and new drug combinations that may offer an opportunity to yield better outcomes.

And, of course, clinical trials are how we make advances in care, so all participants are contributing to moving cancer care forward. The fact that only 5% of patients currently participate in studies is a huge loss for the medical community and a huge opportunity loss for patients.

No matter what, patients should at least be aware that clinical trials are an option and to make sure to leave the door open if they might want to participate. I see so many patients frustrated when they find out they can’t get into a study because they already started treatment. It’s unfortunate. If a patient decides not to proceed with entering a study, that’s fine, but if they have the information beforehand, they can at least make an informed, educated decision. We should allow our patients that opportunity.

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