Vaccine to prevent pancreatic, colorectal cancer relapse yields ‘exciting’ early results
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Results of a phase 1 trial for a vaccine targeting micrometastatic disease markers in patients already treated for pancreatic or colorectal cancer showed potential in preventing recurrence, according to a study in Nature Medicine.
Among the trial cohort, 84% of patients had a positive T-cell response, and those who hit or exceeded the median rate did not reach their median recurrence-free survival. No patients had grade 3 or higher adverse events.
“We see a lot of negative trials [in pancreatic cancer],” Shubham Pant, MD, MBBS, a professor in the department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, told Healio. “It’s early, but promising, that we’ve made a potential impact in this disease, potentially controlling this micrometastatic disease to really give these patients a long-term, disease-free survival.”
Pant spoke with Healio about the first-in-human trial, the “exciting” results, the phase 2 study and more.
Healio: What is the aim of this vaccine?
Pant: With pancreatic cancer, even after resection — when there is no evidence of disease — patients finish their chemo but still have a high chance of the cancer coming back. How do you achieve cures in these patients? You can maybe find a micrometastatic disease and try to control it, or even kill it, with certain therapies, such as vaccines. That’s why this approach is exciting. In the trial, we included patients who were ctDNA positive. In these patients, we saw that once we gave them the vaccine, about 84% either had a tumor marker reduction or a ctDNA reduction.
Healio: What does the vaccine do?
Pant: It goes against two different KRAS mutations — G12D and G12R — and is an off-the-shelf vaccine. The interesting thing about this vaccine is once given, it binds to albumin in the body and goes to the lymph nodes. This increases the T-cell response, which can potentially fight these micrometastatic diseases that we cannot see.
Normally, if a patient has stage IV disease, then it’s harder to target pancreatic cancer through a vaccine. It is a very immunosuppressive microenvironment, so around it is a very desmoplastic stroma, like a hard shell. When the cancer cells have not formed that shell in the early stages, hopefully we can hit them with the vaccine.
Healio: Has this been tried before?
Pant: Another cancer vaccine was published in Nature last year by Vinod Balachandran, MD, from Memorial Sloan Kettering, but you had to take the tumor out and make the vaccine against that — manufacture it. This is off the shelf, so it’s a little bit easier to give to patients.
Healio: What were the key results from the phase 1 study?
Pant: First up, it was safe and tolerable. The main side effect we saw was injection-site reactions. We did not see any dose-limiting toxicities. The second thing, this was from baseline, we did not observe any lesions on scans to follow like we have in stage IV disease. We had biomarkers — CA 19-9 (carbohydrate antigen) or CEA (carcinoembryonic antigen) — or the ctDNA to follow; 84% of patients saw a reduction in the tumor biomarker or in the ctDNA. The third, more exciting part — 84% of patients also mounted a T-cell response.
Interestingly, the median T-cell response was 13 times from baseline. Patients who got a median or more-than-median T-cell response seemed to benefit the most. We scanned these patients with a robust T-cell response every 3 months on the trial and they have not yet reached their median recurrence-free survival. In the patients who did not get this T-cell response, their median recurrence-free survival was about 4 months.
Healio: What was your reaction to the results?
Pant: The results are better than I expected. These patients have a high risk of relapse, and these responses were really exciting to see. I have several patients in my practice who are still alive today.
Healio: How would you describe the toxicities?
Pant: They were better than I expected. Sometimes with these immunotherapies we see cytokine release syndrome, but we really did not see that. It was really well tolerated — 48% had an adverse event such as fatigue, injection-site reactions or 12% myalgia.
Healio: What is happening in phase 2?
Pant: In the next phase, we are not even requiring patients to be ctDNA positive. It’s a randomized trial and we’re broadening the patient population. They don’t even need to be as high risk as the patient population in our phase 1 study. Enrollees are required to have undergone pancreatic cancer resection and finished adjuvant therapy, chemotherapy or whatever therapy they were on.
It’s a seven-peptide vaccine, so more mutations are targeted with a dose level of 10 mg, based on phase 1 results. We are already starting to accrue patients to this trial. Hopefully we’ll get the trial approved this year and the results will probably be available sometime next year.
Healio: What questions do you want answered?
Pant: I want to see more robust T-cell responses in more patients. Hopefully at these higher doses we’ll be able to see a larger volume of robust T-cell responses. The second thing is to see whether the vaccine can delay disease recurrence, and my hope is a cure for some of these patients — a complete cure. We can completely eradicate any micrometastatic disease, which translates hopefully into long-term cures for these patients.
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For more information:
Shubham Pant, MD, MBBS, can be reached at spant@mdanderson.org.
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