OrigAMI-4 Shows 56% Response for Head and Neck Cancer

In an interview with CURE, Dr. Ranee Mehra, director of Head and Neck Oncology in the Division of Hematology/Oncology and associate director for Clinical Research at the University of Maryland School of Medicine, discussed results from the OrigAMI-4 trial evaluating subcutaneous Rybrevant (amivantamab) plus Keytruda (pembrolizumab) in recurrent or metastatic head and neck squamous cell carcinoma.

The study enrolled patients with HPV-unrelated, PD-L1–positive disease whose cancer recurred after prior treatment given with curative intent, including platinum-based therapy. The primary end point was overall response rate, which reached 56%, with 10% of patients achieving a complete response. Median progression-free survival was 7.7 months, and 82% experienced some degree of tumor shrinkage.

Side effects were consistent with expected EGFR, MET and immunotherapy-related toxicities, with fewer infusion-related reactions observed with subcutaneous dosing.

CURE: Can you please explain what the OrigAMI-4 study was designed to find out and why it matters for patients with head and neck cancer?

Mehra: Patients with head and neck cancer who develop recurrent disease are often very symptomatic, and current standard treatment options are limited. The goal of this cohort of OrigAMI-4 was to study the combination of Rybrevant and Keytruda in patients with HPV-unrelated, PD-L1–positive disease, with the hope of seeing improved symptom control and improved efficacy compared with our current standards.

Who in the head and neck cancer community was eligible to join this trial, and how does that group compare with patients in everyday practice?

These were patients who developed recurrence after prior treatment given with curative intent. At least six months had to have passed since prior platinum-based therapy if it was given in the curative setting. As I mentioned before, they had HPV-unrelated disease. Even patients with oropharyngeal cancers had to have confirmation that their tumors were p16-negative. They were also required to have PD-L1 expression of at least 1%, which shows the presence of the immunotherapy biomarker.

What were the main results of the study, especially the response rate, duration of response and how quickly patients saw changes?

The primary end point was overall response rate. The overall response rate was 56%, and about 10% of patients were found to have a complete response. The duration of benefit was durable. The median progression-free survival was 7.7 months, and the median overall survival was not estimable at the time of the data cutoff.

How did patients tolerate the subcutaneous Rybrevant treatment in terms of side effects and overall comfort?

The benefit of subcutaneous dosing is that there is less risk of infusion-related toxicities. That was seen here, with milder and fewer reactions compared with intravenous dosing. Overall, the side effects were what would be expected with EGFR or MET inhibition from Rybrevant, as well as what we typically see with immunotherapy. There were no additional unusual side effects observed with the combination.

What do these results mean for patients’ daily lives, such as symptom relief, quality of life or time without disease progression?

For patients to have better quality of life, they need significant tumor shrinkage. This regimen showed that 82% of patients had some degree of tumor shrinkage. With a high overall response rate and durable benefit, this can translate into better symptom control, less pain, improved ability to maintain nutrition and fewer wound complications, all of which contribute to better quality of life.

What future steps are planned now that OrigAMI-4 has shown these initial results, and how soon might patients see this approach become more widely available?

OrigAMI-4 has an additional cohort that is currently enrolling, including Rybrevant in the perioperative setting. As far as future directions, this regimen should be studied further. There is an ongoing trial in the first-line setting combining Rybrevant with carboplatin for recurrent or metastatic disease. We will be interested to see how those results develop.

When you look at the OrigAMI-4 results, what stands out most, and why are these findings important for patients who have already received immunotherapy and chemotherapy?

In head and neck cancer, anytime we see a regimen that produces responses, durable responses and is tolerable, it gives us hope that this could become a new treatment approach for our patients.

Are there any other clinical trials or studies you are watching that may be presented soon or are currently in development with other agents?

Yes, we are in an exciting time in head and neck cancer treatment. There is significant interest in studying bispecific antibodies, particularly those targeting EGFR. EGFR has been a target of interest in head and neck cancer for more than 20 years. With the availability of dual-targeting agents, we are seeing greater efficacy in clinical trials. In addition to Rybrevant, there will be data presented on other bispecific agents in ongoing clinical trials.

Do you have any final thoughts or advice for patients or caregivers who are deciding on treatment?

It is very difficult to go through treatment for this type of cancer, especially if there is recurrence after significant effort to cure the disease. That can be challenging for patients and caregivers. There are many quality-of-life considerations, including pain, nutrition and speech. It is important to be aware of available treatment options and to explore clinical trials, particularly in the recurrent setting. While we do have good standard options, there is still room for improvement, and clinical trials help us study new approaches.

References

1. “Subcutaneous amivantamab monotherapy in patients with HPV-unrelated recurrent or metastatic head and neck squamous cell carcinoma from the OrigAMI-4 study” by Dr. Kevin J. Harrington, et al. Oral Oncology.

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