Findings from the phase 3 ADAM trial (NCT03271372) of adjuvant avelumab (Bavencio) could inform the design of future adjuvant studies performed in patients with high-risk stage III Merkel cell carcinoma (MCC), according to Shailender Bhatia, MD.
Findings from the double-blinded, placebo-controlled, phase 3 study were shared during the 2026 ASCO Annual Meeting and showed that avelumab (n = 48) resulted in a numerical improvement in relapse-free survival (RFS) vs placebo (n = 52) in this population (stratified, age-adjusted HR, 0.55; 95% CI, 0.28-1.06; P = .075).1 Moreover, exploratory findings showed that avelumab reduced the risk of MCC relapse by approximately 50% (stratified, age-adjusted HR, 0.47; 95% CI, 0.24-0.95).
“[These are] the first prospective data that we have from randomized trials in MCC, and our trial distinguishes itself from other adjuvant trials in that it focuses on the highest-risk patients,” Bhatia said in an exclusive interview with OncLive®.
In the interview, Bhatia discussed next steps for adjuvant therapy research and broader implications for the field of MCC. Bhatia is director of the Melanoma and Renal Cancer Team and holds the Lyn and Daniel Lerner Endowed Chair for Merkel Cell Carcinoma at Fred Hutch and is a professor in the Division of Hematology and Oncology at the University of Washington School of Medicine.
OncLive: In the first portion of our interview, you mentioned an age imbalance between arms. What should be known about that as it relates to the sensitivity analyses performed in the trial?
ADAM Trial: Next Steps and Broader Significance in Merkel Cell Carcinoma
- Sensitivity analyses adjusting for baseline imbalances between arms did not qualitatively change the ADAM trial's results (unadjusted stratified HR for RFS, approximately 0.6).
- The ADAM trial represents the first prospective randomized data in patients with high-risk stage III Merkel cell carcinoma, distinguishing it from prior adjuvant studies conducted in lower-risk disease.
- Investigators are also presenting separate data suggesting the timing of immunotherapy infusions does not meaningfully affect outcomes, a question of growing interest given data in other tumor types.
Bhatia: We did have a prespecified adjustment for confounding variables built into our protocol, and we did that. Age was the only variable that was statistically different between the two groups. Numerically, the avelumab group also had a higher proportion of [males], which is also associated with poorer outcomes, and somewhat higher ECOG scores. We did sensitivity analyses adjusting for those, and [none] of those qualitatively changed our results. Even if you don't adjust for it, the stratified HR is around 0.6, which is still impressive as compared with many other adjuvant settings.
What is the significance of the ADAM trial data?
Dissemination of these data is going to be important. It will be interesting to see how the scientific community reacts to these data, but my hope is that [they] will guide the discussions for many years to come, and not just in the clinic, but also on the research side…Hopefully, these data are going to guide the future generation of trials while it informs us in the clinic.
What research presented at ASCO 2026 will be most significant in your field this year?
I would like to propose that our study is going to be informative. One thing that we are missing in most adjuvant and neoadjuvant trial discussions is we are focusing on the short-term end points of [RFS], but as the MCC data point out, that does not necessarily mean we have to treat all of our patients with adjuvant therapy. We need to strive for longer-term survival benefit when it comes to adjuvant therapy.
The other thing I would like to highlight is we are also presenting an abstract on the timing of immunotherapy infusions, which has been a hot area lately; a lot of studies have pointed out that morning or early infusions of immunotherapy might have better outcomes, which a lot of clinics are now even thinking about adopting, which poses huge logistical challenges. We looked at that data at our center; we have been using immunotherapy for 15-plus years, and we basically see no difference in outcomes based on the timing of immunotherapy infusions, which makes intuitive sense based on the mechanism of action of these drugs, and also the fact that these antibodies last in the serum for months after administration. I'm hoping we will stir some more conversation in that controversial field.
Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
References
- Bhatia S, Gooley T, Brohl AS, et al. ADAM trial: a multicenter, randomized, double-blinded, placebo-controlled, phase 3 trial of adjuvant avelumab (anti-PD-L1 antibody) in patients with Merkel cell carcinoma and lymph node metastases. J Clin Oncol. 2026;44(17_suppl):LBA9504. doi:10.1200/JCO.2026.44.17_suppl.LBA9504
- McEvoy AM, Lachance K, Hippe DS, et al. Recurrence and mortality risk of Merkel cell carcinoma by cancer stage and time from diagnosis. JAMA Dermatol. 2022;158(4):382-389. doi:10.1001/jamadermatol.2021.6096
