Head and Neck Oncologists Highlight Practice-Informing Research From ASCO 2026

During the 2026 ASCO Annual Meeting, head and neck cancer experts noted the studies and investigational agents that hold the most promise for treatment paradigm shifts for head and neck squamous cell carcinoma (HNSCC), adenoid cystic carcinoma (ACC), and beyond.

Abstract 6008: Amivantamab in HPV-unrelated recurrent/metastatic head and neck squamous cell cancer after disease progression on immune checkpoint inhibitor and chemotherapy: Pivotal results from the phase 1b/2 OrigAMI-4 study

Findings from cohort 1 of the phase 1b/2 OrigAMI-4 trial (NCT06385080) showed high, deep, and durable response rates among patients with recurrent or metastatic head and neck squamous cell carcinoma who received amivantamab and hyaluronidase-lpuj (subcutaneous amivantamab; Rybrevant Faspro) monotherapy following a PD-(L)1 inhibitor and platinum-based chemotherapy (n = 102).¹

The confirmed overall response rate was 42% (95% CI, 32%-52%), including a complete response (CR) rate of 15%. Among confirmed responders (n = 43), the median duration of response was not reached (NR; 95% CI, 6.9 months-NR), and as of the data cutoff, CRs were ongoing in 87% of patients with a CR (n = 15). Additionally, the median progression-free survival was 6.8 months (95% CI, 5.2-8.3), and the median overall survival was 12.5 months (95% CI, 10.2-16.8).

Jacob Thomas, MD

University of Southern California

“[OrigAMI-4 ] is a promising study. [Amivantamab is] one of many EGFR-directed bispecific antibodies. Over the next year or 2, we’re expecting to see data read out from many of these studies, but [this amivantamab presentation] showed promising data.” 

Abstract 6063: PD-L1 CPS ≥10 population subgroup analysis of KEYNOTE-412: Pembrolizumab plus chemoradiotherapy versus placebo plus chemoradiotherapy for unresected locally advanced head and neck squamous cell carcinoma

The end-of-trial analysis of the phase 3 KEYNOTE-412 study (NCT03040999) showed that a higher PD-L1 combined positive score (CPS) may be associated with improved event-free survival (EFS) and overall survival (OS) outcomes in patients with resectable, locally advanced HNSCC who receive pembrolizumab (Keytruda) plus chemoradiotherapy followed by maintenance pembrolizumab, vs those who receive placebo plus chemoradiotherapy followed by maintenance placebo.²

In the pembrolizumab arm (n = 302), the median EFS was 71.8 months (95% CI, 55.4-not reached [NR]) vs 49.8 months (95% CI, 26.8-66.2) in the placebo arm (n = 402; HR, 0.79; 95% CI, 0.65-0.96). The median OS in these respective arms was NR (95% CI, 70.3 months-NR) vs 61.4 months (95% CI, 33.7-NR; HR, 0.71; 95% CI, 0.53-0.97).

Barbara Burtness, MD

Yale Cancer Center

“These data were presented in the poster session, but they could be practice changing. This was an 804-patient study and was open to any patients who had high-risk disease and were eligible for definitive chemoradiation, and it included patients who were PD-L1 nonexpressing, those who had human papillomavirus (HPV)–associated disease, and those with stage III disease. This study has previously been reported as negative, although with longer follow-up, a difference is emerging in favor of pembrolizumab. At this meeting, analyses in the PD-L1–enriched cohort were presented, using a cut point of a CPS of 10 or higher. These were unplanned post hoc analyses, so no P values, but at 5 years, there was an EFS advantage for adding pembrolizumab, and the CIs did not cross 1. There was also an OS advantage with the use of pembrolizumab at 5 years, and the [CIs] did not cross 1. The patients with HPV-associated cancers did not seem to benefit, nor did those with stage III disease. However, if you’re sitting in clinic with a patient who has an HPV-negative, stage IV, CPS 10 or higher head and neck cancer for whom you’re going to offer definitive chemoradiation, should you be telling that patient, ‘there’s a treatment that’s not FDA approved, but it looks like it adds to your 5-year survival rate’? Hopefully, those data will be taken to the National Comprehensive Cancer Network and ESMO for consideration to go into the guidelines.”

Abstract 6010: Emiltatug ledadotin (Emi-Le), a B7-H4–directed antibody-drug conjugate (ADC), in patients with aggressive adenoid cystic carcinoma (ACC): Phase 1 interim analysis

In the interim analysis of a phase 1 trial (NCT05377996), the antibody-drug conjugate emiltatug ledadotin (Emi-Le; XMT-1660) showed clinical activity and a manageable safety profile in patients with ACC.³

Treatment discontinuations due to treatment-related adverse effects (TRAEs) were uncommon, occurring in 2.1% of patients in the ACC cohort (n = 48). Overall, any TRAEs were reported in 100% of patients in this cohort, and grade 3 TRAEs were seen in 79.2% of patients in this cohort. A post hoc analysis showed that among efficacy-evaluable patients, the confirmed overall response rate was 46.9% (95% CI, 29.1%-65.3%), the disease control rate was 81.3% (95% CI, 63.6%-92.8%), and the median duration of response was 6.4 months (95% CI, 3.1-9.5).

Abstract 6009: Clinical activity of REM-422, a MYB mRNA degrader, in recurrent/metastatic adenoid cystic carcinoma: Final results from the phase 1/2 dose-escalation cohort

The final analysis of the dose-escalation cohort of a phase 1/2 trial (NCT06118086) showed that among patients with recurrent/metastatic ACC who received the first-in-class small molecule MYB degrader REM-422, the agent was well tolerated at the recommended phase 2 dose (RP2D) of 24 mg and showed antitumor activity in patients with poison exon–positive disease.⁴ In biomarker-positive patients, the overall response rate was 43%, and the disease control rate was 100% at the RP2D.

Katharine Price, MD

Mayo Clinic

“There are 2 exciting drugs for ACC. It’s unprecedented in the history of head and neck cancer. There’s a MYB degrader that was presented by Renata Ferrarotto, MD, from The University of Texas MD Anderson Cancer Center, that is showing promising activity. Then Glenn Hanna, MD, from Dana-Farber Cancer Institute, presented on Emi-Le, a B7-H4–directed [antibody-drug conjugate] for the more aggressive types of ACC. Going forward, at least in the years to come, there’s going to be a lot of focus on those 2 drugs, since they’re the most promising, historically, in the history of ACC to date. All the other treatments we use [or will soon use] for ACC, like lenvatinib, pemetrexed, and pembrolizumab, will be [used] further down the line. But the reality is that none of these drugs is a cure. Some of what we’ll be figuring out over the years is who benefits, the order [of these therapies], and when it’s appropriate to use one over the other. There’s still a lot of important work to be done in the years to come.”

Glenn Hanna, MD

Dana-Farber Cancer Institute

“At ASCO 2026, for head and neck cancer, I’m most excited about the potential for the future of ADCs. We’re starting to see several trials showing that these drugs are active, particularly the vedotins, across different targets. It’s still early days, and we have some toxicity mitigation to do, but bringing ADCs to advanced, recurrent/metastatic head and neck cancer is of strong interest. Regarding the experience with salivary cancer, a tremendously important and rare subtype with high unmet need, the clinical science symposia highlighted data from Emi-Le and the REM-422 trial, which is investigating a novel oral MYB degrader, [that] all look compelling and could give us a new day for salivary tumors, where we could have more than 1 approved option in the years to come.”

References

1. Burtness BA, Harrington KJ, Ji D, et al. Amivantamab in HPV-unrelated recurrent/metastatic head and neck squamous cell cancer after disease progression on immune checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. J Clin Oncol. 2026;44(suppl 16):6008. doi:10.1200/JCO.2026.44.16_suppl.6008
2. Burtness B, Tao Y, Siu LL, et al. PD-L1 CPS ≥10 population subgroup analysis of KEYNOTE-412: pembrolizumab plus chemoradiotherapy versus placebo plus chemoradiotherapy for unresected locally advanced head and neck squamous cell carcinoma. J Clin Oncol. 2026;44(suppl 16):6063. doi:10.1200/JCO.2026.44.16_suppl.6063
3. Hanna GJ, Rabinowits G, Attarian S, et al. Emiltatug ledadotin (Emi-Le), a B7-H4–directed antibody-drug conjugate (ADC), in patients with aggressive adenoid cystic carcinoma (ACC): phase 1 interim analysis. J Clin Oncol. 2026;44(suppl 16):6010. doi:10.1200/JCO.2026.44.16_suppl.6010
4. Ferrarotto R, Swiecicki P, HO AL, et al. Clinical activity of REM-422, a MYB mRNA degrader, in recurrent/metastatic adenoid cystic carcinoma: final results from the phase 1/2 dose-escalation cohort. J Clin Oncol. 2026;44(suppl 16):6009. doi:10.1200/JCO.2026.44.16_suppl.6009