# Sequencing DLL3 engager and B7-H3 ADC in relapsed SCLC

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

## TL;DR

Two new relapsed-disease options with different targets and mechanisms. Which comes first, and whether one works after the other, is unknown.

## Summary

This sequencing question in relapsed small-cell lung cancer concerns tarlatamab, a DLL3-directed T-cell engager, and ifinatamab deruxtecan (I-DXd), a B7-H3-directed antibody-drug conjugate with a topoisomerase 1 payload. Tarlatamab has shown a survival benefit in DeLLphi-304, while I-DXd has produced high response rates and is in the phase 3 IDeate-Lung02 trial. Because the two drugs hit different antigens and kill by different mechanisms, they are expected not to be cross-resistant, and their toxicity profiles also differ, cytokine release syndrome for one and interstitial lung disease and neutropenia for the other, which could allow a patient-based choice. No prospective data yet say which should come first or whether one works after the other, so the pairing remains a concept.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Tarlatamab + Ifinatamab deruxtecan
- Type: sequence
- Rationale: Distinct targets and killing mechanisms; toxicity profiles (CRS vs ILD/neutropenia) also differ, allowing patient-based choice.
- Evidence: No prospective sequencing data; concept.

## Connected records

- cancers: [Extensive-stage small-cell lung cancer](https://onco.cc/cancers/extensive-stage-sclc/), [Small-cell lung cancer](https://onco.cc/cancers/sclc/)
- targets: [B7-H3](https://onco.cc/targets/b7h3/), [DLL3](https://onco.cc/targets/dll3/)
- drugs: [Ifinatamab deruxtecan](https://onco.cc/drugs/ifinatamab-deruxtecan/), [Tarlatamab](https://onco.cc/drugs/tarlatamab/)

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