# ADC + checkpoint inhibitor

Source: https://onco.cc/pairings/adc-plus-io/  
OnCo record `adc-plus-io` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An ADC kills tumour cells in a way that alerts the immune system; a checkpoint inhibitor lets the immune system finish the job.

## Summary

Proven in urothelial cancer (EV-302: enfortumab vedotin + pembrolizumab, OS HR 0.47) and TNBC (ASCENT-04: sacituzumab govitecan + pembrolizumab, PFS HR 0.65, approved 2026). TROPION-Breast05 (Dato-DXd + durvalumab) and multiple lung trials follow. Overlapping pneumonitis risk with DXd ADCs needs care.

## Fields

- Kind: Pairing
- Last checked: 2026-09-04
- Pairs: Antibody-drug conjugate (ADC) + Immune checkpoint inhibitors
- Type: combination
- Rationale: TOP1 and tubulin payloads induce immunogenic cell death, cGAS-STING activation, and antigen release; ADCs also deplete immunosuppressive myeloid cells. PD-1 blockade converts the resulting T-cell priming into durable control.
- Evidence: Phase 3 positive in two tumour types; multiple ongoing.

## Sources

- ClinicalTrials.gov NCT04223856: EV-302 / KEYNOTE-A39: https://clinicaltrials.gov/study/NCT04223856
- ClinicalTrials.gov NCT05382286: ASCENT-04 / KEYNOTE-D19: https://clinicaltrials.gov/study/NCT05382286

## Connected records

- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- drugs: [Enfortumab vedotin](https://onco.cc/drugs/enfortumab-vedotin/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Sacituzumab govitecan](https://onco.cc/drugs/sacituzumab-govitecan/)
- pathways: [cGAS-STING innate sensing](https://onco.cc/pathways/cgas-sting/)
- trials: [ASCENT-04 / KEYNOTE-D19](https://onco.cc/trials/ascent-04/), [EV-302 / KEYNOTE-A39](https://onco.cc/trials/ev-302/), [TROPION-Breast05](https://onco.cc/trials/tropion-breast05/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- ideas: [An oncology patent pool for combination trials across companies](https://onco.cc/ideas/idea-fund-combination-patent-pool/), [Neoadjuvant ADC + IO replacing anthracycline chemotherapy in TNBC](https://onco.cc/ideas/idea-neoadjuvant-adc-io/)

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