ASCO 2024 preview – conjugates in focus

As antibody-drug conjugates continue to generate partnering interest it’s logical that they will feature extensively at ASCO. A perusal of the meeting’s abstracts reveals at least 30 different projects being profiled across posters and oral sessions, spanning nearly 20 different targets and various payloads.

These include a strong showing from HER2 and Claudin18.2, two of the most crowded ADC targets, plus work already highlighted by AbbVie on SEZ6 (ABBV-706) and cMet (telisotuzumab vedotin and ABBV-400). Away from such limelight ASCO will see presentations on an ADC against an entirely new antigen, CD44v9, similarly acting versions of Polivy and Tivdak, and the fruits of various recent deals.

These deals include GSK’s licensing last year of Jiangsu Hansoh’s anti-B7-H3 project HS-20093, whose ASCO abstract claims a 58% ORR in SCLC at the highest doses. Meanwhile, the subject of a tie-up between Corbus and CSPC, the Nectin-4 targeting CRB-701, has yielded an unconfirmed ORR of 50% in a small study in Nectin-4-positive solid tumours.

Nectin-4 is in focus largely because Pfizer’s Padcev scored a home run in urothelial cancer, since when several companies have entered the arena with ADCs against this target. Two other such projects have secured slots at ASCO.

After Seagen

Pfizer recently outlined its post-Seagen strategy, and ASCO features the anti-integrin β6 ADC sigvotatug vedotin, seen by some analysts as one of the key reasons (beyond the Adcetris franchise) for the Seagen acquisition.

The ASCO abstract, covering a late-line NSCLC trial, shows an ORR among 27 patients given 1.8mg/kg of 22%. Sigvotatug vedotin is already in a phase 3 study in second/third-line NSCLC.

Pfizer remains focused on CEACAM5 through the Sanofi-partnered PF-08046050, and the CEACAM5 target is also being pursued by Merck KGaA with M9140. This ADC has disappointed, with its ASCO abstract revealing an ORR of just 10% in colorectal cancer. True, this concerns a late-line setting and a relatively low dose, but the dataset includes one death due to sepsis.

Among other recent ADC deals, BioNTech this month signed a second collaboration with MediLink; its first deal, struck last October, covered the anti-HER3 project BNT326/YL202, whose ASCO poster claims a 41% ORR in a first-in-human trial in NSCLC and breast cancer. 

Three years earlier CStone licensed LegoChem’s anti-ROR1 ADC LCB71/CS5001, whose first-in-human ASCO abstract doesn’t reveal efficacy data.

CD44v9

For complete novelty, meanwhile, Multitude Therapeutics has an ASCO presentation on AMT-116, which targets CD44v9 – a target featuring no other industry competition, according to OncologyPipeline.

The other salient aspect of this ADC is that it uses Kelun’s camptothecin (KL610023) payload, rather than Multitude’s own exatecan. This is explained by the fact that last October Kelun licensed to Multitude rights to use its payload and linker to develop “a first-in-class target ADC”, which the ASCO abstract thus reveals to be AMT-116.

Novelty of sorts is also evident in Lepu’s MRG004A and Jiangsu HengRui’s CHS-A1912. Though these ADCs’ targets, tissue factor and CD79b respectively, already feature marketed competitors (Pfizer’s Tivdak and Roche’s Polivy), there has been relatively little work to develop similarly acting molecules.

Selected ADCs being presented at ASCO 2024

Source: ASCO.

The ASCO annual meeting takes place in Chicago on 31 May to 4 June.