Experimental Treatment Shrinks Tumors in Aggressive Adenoid Cystic Carcinoma

Patients with aggressive adenoid cystic carcinoma (ACC), a rare cancer that typically arises in the salivary glands, often face limited treatment options when their disease returns or spreads. New data presented at the 2026 ASCO Annual Meeting suggest that an investigational therapy called emiltatug ledadotin (also known as Emi-Le) may offer meaningful tumor responses and disease control for this underserved patient population.

According to Dr. Glenn Hanna, a head and neck cancer specialist at Dana-Farber Cancer Institute, the findings could represent a significant advance for patients with recurrent or metastatic ACC.

"Right now, there are no approved options," Hanna said during an interview at ASCO 2026. "Emi-Le would really be a game changer for aggressive adenoid cystic carcinoma."

What Is Adenoid Cystic Carcinoma?

ACC is a rare cancer that develops in salivary glands and other glandular tissues. While many patients are successfully treated with surgery and radiation when the disease is localized, recurrence can occur years later. Some patients develop metastatic disease, and there is currently no established standard treatment specifically approved for advanced ACC.

Historically, doctors have relied on clinical trials, chemotherapy or off-label targeted therapies. However, these approaches have generally produced modest benefits.

"Unfortunately, immunotherapy doesn't work well," Hanna explained. "We're talking about response rates potentially in the single digits, maybe less than 10%, with progression-free survival estimates of only a couple months."

How Does Emiltatug Ledadotin Work?

Emiltatug ledadotin is an antibody-drug conjugate (ADC), a type of targeted therapy that combines an antibody with a cancer-killing drug.

The treatment targets a protein called B7-H4, which is commonly found on ACC tumor cells, particularly in more aggressive forms of the disease. Once the drug attaches to cancer cells expressing B7-H4, it delivers its chemotherapy payload directly into those cells.

Researchers evaluated the therapy in patients with recurrent or metastatic ACC as part of an early-phase clinical trial designed to assess safety and preliminary effectiveness.

Promising Response Rates Seen

Among patients with aggressive ACC, investigators observed response rates approaching 40% and even higher in some subgroups.

In addition to shrinking tumors, the responses appeared durable, allowing many patients to remain on treatment for extended periods.

Researchers also reported progression-free survival approaching eight to nine months, compared with historical expectations of approximately two months.

"So again, a tremendous improvement and really a potential game changer drug for adenoid cystic carcinoma," Hanna said.

The promising results recently contributed to the therapy receiving Breakthrough Therapy designation from the FDA.

Safety Profile Appears Manageable

Another encouraging aspect of the study involved safety.

Hanna noted that many side effects commonly associated with other antibody-drug conjugates were not frequently observed with emiltatug ledadotin.

Investigators reported low rates of:

• Eye-related side effects
• Lung inflammation
• Significant blood count abnormalities

The most notable side effect was proteinuria, or protein in the urine. However, Hanna said the condition has generally been manageable and often can be treated with kidney-supportive medications without requiring patients to stop therapy.

Identifying Patients Most Likely to Benefit

Researchers found that the strongest responses occurred in patients with what they describe as "aggressive" ACC.

Rather than relying solely on complex molecular testing, physicians can often identify this subtype using features already available through routine pathology and clinical evaluation.

Characteristics associated with aggressive ACC include:

• Tumors containing solid growth patterns
• High-grade transformation on pathology
• Recurrence within approximately three years of initial treatment
• Metastases outside of the lungs

Hanna emphasized that these features should be recognizable to both community oncologists and specialists.

"Community physicians, as well as physicians who don't see a lot of ACC, should be able to identify and therefore choose patients who may benefit from Emi-Le" he said.

What These Findings Mean for Patients

Although overall survival data remain immature, Hanna said the current findings provide reasons for optimism when discussing clinical trial participation with patients.

"When I talk to patients about Emi-Le in the context of the trial, I'm able to share that the response rate is quite compelling," Hanna said.

He explained that physicians are seeing several encouraging signs:

• Tumor responses in more than 40% of patients with aggressive disease
• Responses lasting longer than six months in many patients
• Progression-free survival substantially longer than historical expectations

Hanna noted that while researchers cannot yet say whether the treatment helps patients live longer, the durability of responses and improvements in progression-free survival are positive indicators.

"The median is approaching eight months or longer," Hanna said. "Those are nice surrogates, both durability and progression-free time, that lend to likely predicting an improvement in overall survival."

For patients considering enrollment in future studies, those findings may help provide context while investigators continue to collect longer-term follow-up data.

Looking Ahead

While additional research is needed before emiltatug ledadotin could become a standard treatment, the early results are generating excitement in a disease area where few advances have been made.

Hanna also highlighted antibody-drug conjugates as one of the most promising areas in head and neck cancer research overall, suggesting that therapies like emiltatug ledadotin may represent the beginning of a broader shift in treatment options for patients with rare salivary gland cancers.

For patients with aggressive ACC, a disease that historically has had few effective therapies, the investigational drug may offer hope that more targeted and effective options are on the horizon.

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