ESMO 2024 – MediLink impresses in small-cell lung cancer
The group’s B7-H3 ADC looks competitive versus rival projects from Merck/Daiichi and GSK/Hansoh.
The group’s B7-H3 ADC looks competitive versus rival projects from Merck/Daiichi and GSK/Hansoh.
The field of B7-H3 antibody-drug conjugates, which has been a popular hunting ground for deals, has a new contender. Early data released at ESMO on Friday suggest that MediLink’s YL201 could be competitive against candidates originated by Daiichi Sankyo and Hansoh Pharma, which tempted Merck & Co and GSK respectively.
YL201, which is as yet unpartnered, looks particularly good in second-line or later small-cell lung cancer. This tumour type has recently seen data with both Merck/Daiichi’s ifinatamab deruxtecan and GSK/Hansoh’s GSK5764227, allowing a handy cross-trial comparison.
A 61% confirmed response rate with YL201 looks in line with the competition; when unconfirmed responses were also taken into account the response rate rose to 68%.
Cross-trial comparison of B7-H3 ADCs in relapsed SCLC
YL201 | Ifinatamab deruxtecan | GSK5764227 | |
|---|---|---|---|
| Company | MediLink | Merck/Daiichi | GSK/Hansoh |
| ADC details | Topo 1 inhibitor payload; DAR 8 | Topo 1 inhibitor payload; DAR 4 | Topo 1 inhibitor payload; DAR 4 |
| Study | Global ph1 & China phase 1/2 | Ph2 Ideate-Lung01 | Ph1 Chinese Artemis-001 |
| Cutoff | 9 Aug 2024 | 25 Apr 2024 | 30 Jun 2024 |
| ORR | 61% (44/72) | 55% (23/42)* | 61% (19/31)^ |
| mPFS | 6.2mo | 5.5mo* | 5.9mo^ |
Notes: *12.0mg/kg; ^8mg/kg. Source: ESMO & IASLC.
Most patients received YL201 at 2.0mg/kg or 2.4mg/kg every three weeks, the recommended go-forward dose. Dose-limiting toxicities were seen at 2.8mg/kg and 3.0mg/kg every three weeks.
Indeed, toxicity was high, with seven treatment-related adverse events leading to death across all doses, amounting to 2% of patients; still, there were “only” three cases of treatment-related interstitial lung disease. The discussant, Dr Lillian Siu of the Princess Margaret Cancer Centre in Toronto, noted that toxicity wasn’t surprising given YL201’s mechanism of action. She raised the possibility of combining the project with DLL3-targeting agents, such as Amgen’s Imdelltra, in SCLC.
MediLink reckons its tumour microenvironment “activable” linker-payload (Tmalin) technology could promote accumulation in the tumour and reduce off-target toxicity. However, it has previously run into problems, with its BioNTech-partnered HER3 ADC, BNT326, going on clinical hold recently over tox, although this was quickly resolved.
MediLink is planning phase 3 trials of YL201 in SCLC and nasopharyngeal carcinoma – in the latter it saw a confirmed ORR of 47% among 70 patients.
The B7-H3 ADC space is crowded, but there aren’t too many big players involved. Maybe one might be tempted to take a punt on MediLink.
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