What Does Antibody-Drug Conjugate Mean?

This page is for anyone who sees "antibody-drug conjugate" or "ADC" in a treatment plan or clinic note. It explains how these drugs work, four common examples, their main side effects, and when to call.

An antibody-drug conjugate, usually shortened to ADC, is one molecule built from three pieces.

The antibody is the aiming system. It is designed to stick to a specific protein found on the surface of certain cancer cells.

The payload is a drug that kills cells.

The linker joins them.

NCI's dictionary describes it this way. The antibody binds to specific proteins on certain cells, including cancer cells, and the linked drug enters those cells and kills them. The FDA label for each drug below carries serious warnings, which are listed further down.

The FDA prescribing information for each drug names the target, the payload type and the first approval year. The label also lists the approved uses and the dosing. Uses change over time, so ask your team which use applies to you.

Trastuzumab deruxtecan (Enhertu). The label calls it a HER2-directed antibody and topoisomerase inhibitor conjugate. HER2 is the human epidermal growth factor receptor 2. Its first U.S. approval was in 2019. The label lists several uses. They include HER2-positive, HER2-low and HER2-ultralow breast cancer, lung cancer with a HER2 gene change, HER2-positive stomach cancer, and other HER2-positive solid tumors. Many of these uses are for people who had earlier treatment. It is given by vein every 3 weeks. The weight-based amount depends on the cancer.

Brentuximab vedotin (Adcetris). The label calls it a CD30-directed antibody and microtubule inhibitor conjugate. The payload is monomethyl auristatin E, shortened to MMAE. Its first U.S. approval was in 2011. The label lists several lymphomas. They include classical Hodgkin lymphoma, anaplastic large cell lymphoma, some other T-cell lymphomas, and a type of large B-cell lymphoma. Some uses are for newly diagnosed disease and some are for disease that came back. The schedule depends on the use. The usual single-drug schedule is every 3 weeks by vein, at a weight-based amount. The label says to reduce the dose in mild liver impairment and to avoid the drug in moderate or severe liver impairment.

Sacituzumab govitecan (Trodelvy). The label calls it a Trop-2-directed antibody and topoisomerase inhibitor conjugate. The payload is SN-38. Its first U.S. approval was in 2020. The label lists certain triple-negative breast cancers and hormone receptor-positive, HER2-negative breast cancer after earlier treatment. It is given by vein on days 1 and 8 of each 21-day cycle, at an amount based on body weight.

Enfortumab vedotin (Padcev). The label calls it a Nectin-4-directed antibody and microtubule inhibitor conjugate. Nectin-4 is an adhesion protein on the surface of cells. The payload is again MMAE. Its first U.S. approval was in 2019. The label lists urothelial cancer, which is cancer of the bladder and urinary tract lining. Some uses combine it with pembrolizumab, including muscle invasive bladder cancer before and after surgery. It is dosed by body weight, up to a ceiling. Alone, it is given on days 1, 8, and 15 of a 28-day cycle. With pembrolizumab for advanced urothelial cancer, it is given on days 1 and 8 of a 21-day cycle.

The payloads sort into two groups.

Microtubule inhibitors, meaning the vedotin drugs. The labels for both Adcetris and Padcev list peripheral neuropathy among their warnings. That is nerve damage that can cause numbness, tingling, or weakness, in the hands or feet.

Topoisomerase inhibitors, meaning deruxtecan and govitecan. The Trodelvy label has a boxed warning for severe neutropenia and severe diarrhea. The Enhertu label lists low blood cell counts and nausea among its most common side effects.

This is why "targeted therapy" can be misleading. The aiming is targeted. The payload is still a cell-killing drug.

• Interstitial lung disease. The Enhertu label has a boxed warning for interstitial lung disease and pneumonitis, including severe, life-threatening and fatal cases. It tells patients to report symptoms right away. The Padcev label lists pneumonitis and interstitial lung disease as a warning.
• Severe neutropenia and severe diarrhea. The Trodelvy label has a boxed warning for both. It says to monitor blood cell counts during treatment.
• Serious skin reactions. The Padcev label has a boxed warning for severe and fatal skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis. The Adcetris label lists serious dermatologic reactions as a warning.
• Progressive multifocal leukoencephalopathy. This is a brain infection caused by the JC virus. The Adcetris label has a boxed warning for it.
• Heart effects. The Enhertu label lists left ventricular dysfunction as a warning. It says to assess the heart's ejection fraction before treatment and at regular intervals.
• Embryo-fetal toxicity. The labels for all four drugs list it, so contraception planning is part of starting any of them.

• Call 911 or go to the nearest emergency department for trouble breathing, chest pain, sudden confusion, being hard to wake, severe belly pain, or bleeding you cannot stop. Do not drive yourself.
• Call your care team right away, day or night, for a temperature of 100.4°F (38°C) or higher. CDC says to call your doctor right away at that temperature. The Trodelvy label says to withhold the drug for neutropenic fever. Talk to your care team before you take a fever reducer. NCI says medicines such as acetaminophen may hide signs of a more serious problem. Use the 24-hour number, and go to an emergency department if nobody answers.
• Also call right away, day or night, for chills, sweats, a new cough, a sore throat, mouth sores, urination problems, or redness or swelling at a port or wound. CDC lists these as signs of infection during chemotherapy. A normal temperature is not a reason to wait.
• Diarrhea. NCI says to tell your doctor or nurse if you have diarrhea. NCI says seven or more bowel movements above your normal daily number can be life-threatening and may need treatment in a hospital. Count, do not estimate. Call right away, day or night, if you reach that number, or if diarrhea comes with fever, dizziness or lightheadedness.
• New or worsening cough, breathlessness, or chest tightness. These can be signs of interstitial lung disease. Call right away, day or night.
• Numbness, tingling or weakness in your hands or feet. Call your care team right away.
• A rash that blisters, peels, or involves the mouth or eyes. Call right away. The Padcev label calls for withholding the drug for suspected severe skin reactions.

Seeing "antibody-drug conjugate" in a note does not identify which drug, which line of treatment, or whether you are eligible. The FDA labels tie several uses to a target. An ADC aimed at HER2 uses an FDA-authorized test for HER2 on your tumor. Some Adcetris uses are for CD30-expressing disease.

It also does not tell you the schedule. Compare the four above: every three weeks, versus days 1 and 8 of 21, versus days 1, 8, and 15 of 28. Those make very different demands on your calendar, your rides, and your time off work.

• Which ADC, and what protein does its antibody target?
• Was my tumor tested for that protein, and what was the result?
• Is the payload a microtubule inhibitor or a topoisomerase inhibitor?
• How is my dose worked out, and which days of the cycle do I come in?
• What baseline tests happen first, such as a heart check or lung imaging?
• What symptom means I stop the next dose rather than push through?

For related reading, see Targeted Therapy vs Chemotherapy, Biomarker Testing and Precision Medicine, and Antibody-Drug Conjugates by Cancer Type.

• FDA prescribing information (DailyMed) — Enhertu
• FDA prescribing information (DailyMed) — Adcetris
• FDA prescribing information (DailyMed) — Trodelvy
• FDA prescribing information (DailyMed) — Padcev
• National Cancer Institute — Antibody-drug conjugate (NCI Dictionary of Cancer Terms)
• National Cancer Institute — Diarrhea and Cancer Treatment
• National Cancer Institute — Infection and Neutropenia during Cancer Treatment
• CDC — Watch Out for Fever
• CDC — Signs and Symptoms of Infection During Chemotherapy