AACR 2026 | HER2 amplification predicts response in a Phase II rectal cancer study

Yeah, so our research team evaluated patients that have locally advanced rectal cancer in the early stage. So this is typically a population of patients that require multiple different types of treatment that have a lot of side effects. So chemotherapy, radiation, and often a morbid surgery are used to definitively manage these patients. And despite these treatments, many patients still have recurrence. So we decided as a research team to see whether intensifying the chemotherapy part of this regimen, which is typically given before surgery, with the addition of HER2-targeted treatments in a population that have HER2-amplified tumors, would help enable deeper responses, complete clinical responses, and potentially avoidance of surgery and radiation too. So we started this study at our center. It’s a single institution study, a single arm trial. And we started by screening all of the patients that have rectal cancer to evaluate patients that have HER2 amplification. We found that about 2.4% of patients across our center had HER2 amplification on our prospective screen, which was a pretty low percent, but still important population. And then we approached these folks, and out of those patients that were evaluated, 10 patients were consented to the study. So we have 10 patients on the study now. Out of those 10 patients, nine patients completed the first step of the study, which is basically involving giving patients HER2 therapy alone. So we gave patients HER2 therapy alone, which was two different drugs, trastuzumab and tucatinib, for a total of six weeks. And then we had an exploratory assessment. After that first six weeks, we then added an additional 15 weeks of chemotherapy, which was either CAPOX or FOLFOX, combined with the trastuzumab and tucatinib. So there was this lead-in period of six weeks followed by the additional 15 weeks. So the overall treatment period was about five months. After the five-month period, the patients had their main assessment to see whether the tumor was still present or not, and we evaluated them with endoscopy, an MRI scan, and a biopsy, as well as a CAT scan. So after the initial six-week period, nine of the patients have completed that so far. Out of those nine patients, seven patients had a dramatic response just to HER2 therapy alone after only six weeks, which is pretty exciting. The other two patients had stable disease, and no patient progressed on therapy or had a major side effect that made them discontinue treatment. The main assessment, though, is after the five-month time point, which included both the initial six-week period as well as the additional 15-week period with chemotherapy. So out of those 10 patients, again, eight patients so far have completed the entire period of induction chemotherapy with the HER2 treatments. Out of those eight patients, half of them, or four patients, 50% exhibited a complete clinical response, meaning their tumor was not present on MRI scan, CAT scan, exam, or biopsy at the end of that 15-week period. So all of those patients entered non-operative management with surveillance. I will say we did have, oh, and then we had an additional patient who did not undergo a complete clinical response with HER2 treatment and chemo, but had a complete response after radiation was given. So we had overall about six patients out of the eight that had a complete clinical response, excuse me, five patients out of the eight that had a complete clinical response without needing surgery. So about 68% of patients didn’t need surgery at all so far in our trial after a median follow-up of about 30 months, which is about two and a half years. Now, one thing that we should mention is there were some recurrences that happened, both in patients that had a complete clinical response and in one patient that did not have a complete clinical response. Four patients in the study had a recurrence at some point, either a local or distant recurrence. It’s important to mention that the patients that had a complete clinical response, the patients that had a local recurrence, all of them were salvageable without surgery. So we used radiation to treat the tumor in one patient that initially it disappeared but came back. And then another patient had an endoscopic resection, which was done with rectal preservation where they didn’t have their rectum removed. So overall, the conclusions that we drew from the study is that the treatment is very effective at shrinking the tumors. It’s much more than we would expect with traditional chemotherapy. So additional HER2 therapy in this small group of patients was successful. Most of the patients, five out of the eight patients so far, have not had to undergo a major surgery, which is very impressive for this disease, where literally all the patients on our study would have been destined for surgery based on their tumor characteristics. And it’s a small group of people, so the recurrence rate is something that we need to monitor to see whether these treatments can be given definitively to eradicate these tumors or whether additional local therapies such as radiation would be needed. But I think it’s very promising data for activity with these drugs.

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