The Courage of Patients in Phase 1 Cancer Trials

Posted May 31st, 2022 by Rene Russo, in From The Trenches, Science & Medicine, The Human Element

By René Russo, CEO of Xilio Therapeutics, as part of the From The Trenches feature of LifeSciVC

I had the opportunity to witness true courage as I met Chrissy Harding several times before she passed away from advanced lung cancer. Diagnosed in 2016, Chrissy started her treatment journey by following conventional lung cancer regimens available at the time. When she stopped responding to standard therapy, and her cancer progressed, her doctors recommended she try a clinical trial. When she passed away in the summer of 2021, she was in her third early-stage clinical trial. Like Chrissy, many people with end-stage cancer often run out of options with approved treatments and may turn to Phase 1 clinical trials to test potential new cancer treatments. We know this decision takes tremendous courage and we are inspired by them.

Often in drug development, we work hard to move as rapidly as possible through Phase 1 with a focus on progressing to pivotal trials.  But the gravity of Phase 1 clinical trials warrants pausing, reflecting, and acknowledging the sacrifice and courage that patients are making every day when they agree to enroll in this important phase of oncology drug development. A Phase 1 clinical trial is typically the time we are evaluating a new treatment in humans.  These trials are an essential milestone in drug development that involves testing the safety, identifying the best dose, timing, and method of giving a new treatment. Typically, the dose of the new treatment is increased over time, and a lot of information is gathered from the patient about their experience. It is often one of the most data-rich periods in drug development.

Early in my career, I was privileged to work in the Phase 1 development unit at BMS. As a clinical pharmacologist by training, I decided to leave my Medical Affairs role at the time to move to the Clinical Discovery and Experimental Medicine department to learn what happened earlier in the process in the first-in-human studies known as Phase 1 trials.

I had the opportunity in those early years to think about what it meant (and the courage required) for a patient and their family to decide to participate in a Phase 1 trial. It often required them to come to a clinic multiple times to be screened, get blood drawn, often be imaged, and/or biopsied to then get a treatment that had not yet been tested in humans. It is a meaningful time for all involved – the patients, their families, the investigators, and the sponsors. Sometimes important insights emerge, sometimes not, but the bravery of the people involved must be acknowledged and appreciated by all of us when we are developing innovative medicines.

Today, I am back in that seat again at Xilio, thinking of the courageous patients and their families with our two ongoing Phase 1 trials to evaluate our novel tumor-selective immunotherapies and another being planned. Our agents are designed to improve upon the therapeutic index of existing therapies. For instance, in our trial evaluating XTX202, a tumor-selective interleukin-2 (IL-2) we engineered, we aim to localize the molecule’s activity in the tumor microenvironment (TME). IL-2 therapies have curative potential if administered at high-doses but often cannot be given at high enough doses to see that potential without causing life-threatening side effects. XTX202 has been designed to be active only in the TME to reduce dose limiting toxicity and enhance anti-tumor activity. Our Phase 1 trials will provide us with valuable information, with the goal of enabling us to move forward in developing our next-generation tumor-selective immunotherapies.

At a recent company offsite, Xilio’s Head of Clinical Research, Dr. Katarina Luptakova moderated a discussion with a prominent medical oncologist conducting Phase 1 trials. The discussion was meant to help us all pause, understand and appreciate the importance of these trials and how patients were putting their faith and trust in us.  The discussion shed light on how patients know this might not be the right treatment or dose for them but that the Phase 1 trial will help others.  They discussed how researchers starting a Phase 1 clinical trial consider various factors such as the unmet medical need, potential advancement in science, and whether there are unnecessary burdens placed on the patient.

From the beginning of a patient’s interaction with a Phase 1 unit, they are given so much unfamiliar and seemingly bureaucratic information. It is an involved process for patients. Consent is a huge part of the early effort when the patient meets the research team. There is so much information coming at them at once that it can often leave them feeling like they are drinking from a fire hose.

Additional insights regarding managing toxicities to achieve optimal efficacy through combinations, drug sequencing, and tumor agnostic treatments are opportunities for multi-disciplinary teams to collaborate throughout the clinical development process, beginning with those earliest Phase 1 trials.

Our team at Xilio appreciated learning more about Phase 1 clinical trials and the patients, like Chrissy, that take a chance on these treatments to advance the science without a known personal benefit.

Chrissy chronicled her journey on a blog and shared a story about a favorite quote she had displayed on her desk that read “Aut viam inveniam aut faciam” which translates to “I’ll find a way or make one.”  When she was first diagnosed, she said she “realized I’m going to be finding my way with the help of many and that I cannot do it alone.”

I encourage everyone working in oncology Phase 1 trials, to pause and reflect on the debt of gratitude we owe to people like Chrissy.  Without their courage, we wouldn’t be able to find our way to bring new treatments to the people living with cancer starting with Phase 1 clinical trials.  We have dedicated one of our conference rooms in our office to Chrissy as a reminder of what is important in our work. Her courage lives on in all of us.

To learn more about Chrissy, watch this video on our website.

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