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    Antibody-drug conjugates (ADCs)

    Also known as ADCs, antibody drug conjugates, trastuzumab deruxtecan, sacituzumab govitecan, datopotamab deruxtecan

    Antibody-drug conjugates (ADCs) are targeted cancer drugs that link a monoclonal antibody to a highly toxic payload through a chemical linker.[1] They are not immunotherapies, but in 2026 the FDA approved ADC regimens including one combined with the checkpoint inhibitor pembrolizumab.[2]

    Editor reviewedStrict sourcingUpdated Cancer immunotherapyHealth and medicineLife sciences
    Key facts

    Antibody-drug conjugates are included in this crash course as context. They combine the targeting of a monoclonal antibody with the potency of a cytotoxic drug, joined by a chemical linker.[1] Their main mechanism is targeted chemotherapy rather than immune activation, but they increasingly sit alongside checkpoint inhibitors in treatment regimens.[1][2]

    How they work

    An ADC has three parts: a monoclonal antibody that targets cancer cells, a chemical linker, and a cytotoxic payload.[1] Sacituzumab govitecan, for example, is a Trop-2-directed antibody conjugated to a topoisomerase inhibitor.[2] The design aims to concentrate the payload in the tumour and so reduce side effects, but a 2023 review noted that toxicity remains a key issue in developing these drugs.[3] The same review said that as manufacturing matured, many more ADCs had been approved or reached late-stage trials, and that new targets and payloads were widening the range of tumours they can treat.[4]

    2026 approvals

    ADCs had a busy 2026 at the FDA. On 15 May the agency approved trastuzumab deruxtecan for neoadjuvant and adjuvant use in HER2-positive early breast cancer; in DESTINY-Breast05, 3-year invasive disease-free survival was 92.4% versus 83.7% with T-DM1.[5] On 22 May it approved datopotamab deruxtecan for unresectable or metastatic triple-negative breast cancer.[6]

    ADCs with immunotherapy

    The landmark ADC-checkpoint pairing came in bladder cancer. In the phase 3 EV-302 trial, 886 patients with previously untreated locally advanced or metastatic urothelial cancer received enfortumab vedotin plus pembrolizumab or platinum-based chemotherapy. Median overall survival was 31.5 months versus 16.1 months (hazard ratio 0.47), and median progression-free survival 12.5 versus 6.3 months.[7] Serious treatment-related side effects were less common with the combination: 55.9% versus 69.5% had grade 3 or higher events.[8] The FDA approved the regimen on 15 December 2023.[9] It had already granted the combination accelerated approval for patients who could not receive cisplatin-based chemotherapy; EV-302 extended its use to patients with locally advanced or metastatic disease without that restriction.[10][9] In the trial, patients on the combination received a median of 12 treatment cycles, against 6 for chemotherapy.[11] ADCs are increasingly used in combinations, including as first-line therapy.[3]

    On 24 June 2026 the FDA approved sacituzumab govitecan both alone and with pembrolizumab for first-line metastatic triple-negative breast cancer; the combination, for PD-L1-positive disease, achieved median progression-free survival of 11.2 months versus 7.8 months in ASCENT-04.[2]

    Combinations of targeted drugs with checkpoint inhibitors are not limited to ADCs. In August 2026 the FDA also approved the HER2-targeted bispecific antibody zanidatamab with the PD-1 inhibitor tislelizumab in HER2-positive gastroesophageal adenocarcinoma.[12] See bispecific antibodies for that class.

    Why ADCs matter for immunotherapy readers

    Immunotherapy trials increasingly use ADCs either as the comparator or as the partner drug. In ASCENT-03, sacituzumab govitecan alone extended median progression-free survival to 9.7 months versus 6.9 months in patients who could not receive PD-1 or PD-L1 inhibitors.[13]

    Limits of this page

    This page covers ADCs only where they intersect with immunotherapy. Detailed safety profiles are beyond its scope; a 2023 review noted that toxicity remains a key issue in ADC development.[3]

    Questions readers ask

    Is an antibody-drug conjugate a type of immunotherapy?

    Not in the usual sense. An ADC uses an antibody to deliver a highly toxic payload to cancer cells, rather than mainly working by activating the immune system.[1]

    Why are ADCs part of the immunotherapy story?

    They are increasingly combined with checkpoint inhibitors. In June 2026 the FDA approved sacituzumab govitecan with pembrolizumab for first-line PD-L1-positive metastatic triple-negative breast cancer.[2]

    Which ADC approvals came in 2026?

    Examples include trastuzumab deruxtecan in HER2-positive early breast cancer (May), datopotamab deruxtecan in triple-negative breast cancer (May) and sacituzumab govitecan with or without pembrolizumab in first-line triple-negative breast cancer (June).[5][6][2]

    What was EV-302?

    A phase 3 trial in 886 patients with untreated advanced urothelial (bladder) cancer. Enfortumab vedotin plus pembrolizumab gave median overall survival of 31.5 months versus 16.1 months with platinum chemotherapy, and the FDA approved the combination in December 2023.[7][9]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      Antibody-drug conjugates (ADCs) are targeted cancer drugs that link a monoclonal antibody to a highly toxic payload through a chemical linker. confirmedas of 2023-08-01

    2. [2]

      On 24 June 2026 the FDA approved the Trop-2-directed ADC sacituzumab govitecan with pembrolizumab for first-line PD-L1-positive metastatic triple-negative breast cancer; median progression-free survival was 11.2 versus 7.8 months in ASCENT-04. confirmedas of 2026-06-24

    3. [3]

      A 2023 review in Nature Reviews Drug Discovery said ADCs may reduce side effects by preferentially delivering their payload to the tumour, are increasingly used in combination including as first-line therapy, but that toxicity remains a key issue in their development. confirmedas of 2023-06-12

    4. [4]

      The same 2023 review said that as manufacturing technology matured, many more ADCs had been approved or reached late-stage trials, and that more diverse targets and payloads were broadening the tumour types they can treat. confirmedas of 2023-06-12

    5. [5]

      On 15 May 2026 the FDA approved trastuzumab deruxtecan for neoadjuvant and adjuvant use in HER2-positive early breast cancer; in DESTINY-Breast05, 3-year invasive disease-free survival was 92.4% versus 83.7% with T-DM1. confirmedas of 2026-05-15

    6. [6]

      On 22 May 2026 the FDA approved the ADC datopotamab deruxtecan for unresectable or metastatic triple-negative breast cancer. confirmedas of 2026-05-22

    7. [7]

      In the phase 3 EV-302 trial of 886 patients with previously untreated advanced urothelial cancer, enfortumab vedotin plus pembrolizumab roughly doubled median overall survival versus platinum chemotherapy (31.5 vs 16.1 months; hazard ratio 0.47) and progression-free survival (12.5 vs 6.3 months). confirmedas of 2024-03-01

    8. [8]

      In EV-302, treatment-related adverse events of grade 3 or higher occurred in 55.9% of patients on enfortumab vedotin plus pembrolizumab and 69.5% on chemotherapy. confirmedas of 2024-03-01

    9. [9]

      On 15 December 2023 the FDA approved enfortumab vedotin with pembrolizumab for locally advanced or metastatic urothelial cancer, based on EV-302. confirmedas of 2023-12-15

    10. [10]

      Before the December 2023 full approval, the FDA had granted accelerated approval to enfortumab vedotin with pembrolizumab for advanced urothelial cancer patients ineligible for cisplatin-containing chemotherapy. confirmedas of 2023-12-15

    11. [11]

      In EV-302, the median number of treatment cycles was 12 with enfortumab vedotin plus pembrolizumab and 6 with chemotherapy. confirmedas of 2024-03-01

    12. [12]

      On 25 August 2026 the FDA approved zanidatamab, a HER2-targeted bispecific antibody, with the PD-1 inhibitor tislelizumab for first-line HER2-positive gastroesophageal adenocarcinoma; median overall survival was 26.4 versus 19.2 months (hazard ratio 0.72). confirmedas of 2026-08-25

    13. [13]

      In the ASCENT-03 trial (558 patients) supporting the June 2026 approval of single-agent sacituzumab govitecan in first-line metastatic triple-negative breast cancer for patients ineligible for PD-1/PD-L1 inhibitors, median progression-free survival was 9.7 months versus 6.9 months. confirmedas of 2026-06-24

    Revision history (2)
    1. Page created.
    2. Refresh: added EV-302 (enfortumab vedotin plus pembrolizumab) results and approval, and the design rationale and toxicity caveat for ADCs.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "Antibody-drug conjugates (ADCs)." ContentLora, updated Oct 10, 2026. https://contentlora.com/wiki/antibody-drug-conjugates

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