Merck and Daiichi look beyond small cell with ifinatamab
Daiichi Sankyo and Merck & Co are to start a pivotal trial of the B7-H3-targeting ADC ifinatamab deruxtecan in oesophageal cancer, adding to ongoing efforts in small-cell lung cancer. The latest trial, Ideate-Esophageal01, will test ifinatamab-dxd against investigator’s choice chemo in oesophageal squamous cell carcinoma patients who’ve progressed after platinum and checkpoint inhibitors, according to a recently unveiled listing on clinicaltrials.gov. A clue about ifinatamab-dxd’s potential here could come from the phase 1/2 Ideate-Pantumor01 study, which found an ORR of 21% among 28 oesophageal patients with a median of four prior lines of therapy. Keytruda and Opdivo chemo combos are approved in first-line oesophageal cancer, with ORRs of around 45%, but look set to be restricted to PD-L1 expressers. The Ideate-Pantumor01 results could also give an indication of where Merck and Daiichi might go next: the companies have also reported results in late-line castration-resistant prostate cancer and squamous NSCLC. Meanwhile, in SCLC, the groups are now testing a combination of ifinatamab-dxd and the DLL3-targeting T-cell engager MK-6070 – something that looked likely since August, when they teamed up on this asset. MK-6070 was originally developed by Harpoon, which Merck acquired for $680m earlier this year.
Notable trials of ifinatamab deruxtecan
Trial | Setting | Regimen | Primary endpoint(s) | Note |
---|---|---|---|---|
Ph3 Ideate-Lung02 | 2nd-line SCLC | Monotherapy (12mg/kg), vs investigator’s choice | ORR, OS | Primary completion Apr 2027 |
Ph3 Ideate-Esophageal01 | 2nd-line ESCC, post chemo & IO | Monotherapy vs investigator’s choice chemo | OS | Primary completion Oct 2029 |
Ph2 Ideate-Lung01 | 2nd to 4th-line ES-SCLC | Monotherapy, uncontrolled | ORR | Data at WCLC 2024: ORR=26% for 8.0mg/kg; ORR=55% for 12.0mg/kg |
Ph1/2 Ideate-Pantumor01 | Late-line solid tumours | Monotherapy, uncontrolled | Safety, antitumour activity | Data at WCLC & ESMO 2023: ORR 52% in SCLC; 21% in ESCC; 25% in mCRPC; 31% in sq NSCLC |
Ph1/2 HPN328-4001 | 2nd-line ESCC or neuroendocrine tumours | MK-6070 +/- ifinatamab-dxd +/- Tecentriq | PK, safety | Primary completion Feb 2026 |
Ph1/2 Ideate-Lung03 | 1st-line induction/maintenance ES-SCLC | + Tecentriq +/- chemo, uncontrolled | Safety | Primary completion Nov 2026 |
Ph1/2 Ideate-PanTumor02 | 2nd-line solid tumours | Monotherapy, uncontrolled | ORR, safety | Primary completion Jul 2028 |
Notes: all trials global and sponsored by Daiichi, except HPN328-4001, sponsored by Merck. ESCC=oesophageal squamous cell carcinoma; SCLC=small-cell lung cancer. Source: OncologyPipeline & clinicaltrials.gov.
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