ASCO 2025 – Amgen gets one over on Zai Lab

Amgen’s DLL3-targeting T-cell engager Imdelltra looks set to gain full approval in second-line small-cell lung cancer, based on data from its confirmatory trial presented at ASCO on Monday. This throws into doubt a strategy from another DLL3 hopeful, Zai Lab, which is shooting for accelerated approval for its ADC zocilurtatug pelitecan.

During an investor event on Monday, Zai Lab maintained that its plans hadn’t changed, and highlighted zoci-P’s different modality and “ease of administration”. Zai plans to start its registrational trial this year, but is still nailing down some key details.

One of these is the go-forward dose of zocilurtatug pelitecan, previously known as ZL-1310. Another is whether Imdelltra would be part of the control arm. “The FDA hasn’t asked us to include it,” said Zai’s head of global R&D, Rafael Amado, but he added that even if this was required Imdelltra wasn't available in many countries, so “if we start the study soon, in the control arm we don’t expect [Imdelltra use] to be overly high”.

Dellphi-304

Amado seemed certain that Imdelltra was heading for full approval, and for good reason: the confirmatory Dellphi-304 trial, which was also published in the NEJM, found a convincing overall survival benefit with Imdelltra versus chemo in second-line SCLC, at 13.6 months and 8.3 months respectively.

Dellphi-304 results in second-line SCLC

Source: ASCO & NEJM.

Perhaps just as importantly, adverse events didn’t seem too troublesome. When Imdelltra gained US accelerated approval last year it came with a black box warning for cytokine release syndrome and neurologic toxicity including ICANS, but in Dellphi-304 CRS was mostly low grade, with only 1% at grade 3, and none at grade 4 or 5.

There was one death from ICANS deemed possibly related to Imdelltra but, during ASCO, Amgen’s vice-president of oncology global development, I-Fen Chang, told ApexOnco that the patient had “several comorbidities” and contended that, overall, “the incidence of severe ICANS is quite low”.

She declined to say when Amgen would file Imdelltra with the FDA for full approval.

Confirmed vs unconfirmed

Meanwhile, in an ASCO poster, Zai reported promising phase 1 results with the Medilink-originated zoci-P – although perhaps not as promising as these looked last year.

Zai claimed an ORR of 79% among 14 second-line patients receiving 1.6mg/kg, the dose it hopes to take forward – but this included unconfirmed responses. Taking only confirmed responses into account, ORR dropped to 57% with this dose. This still looks better than Imdelltra’s 35% ORR, and Robert Brown, Zai's chief medical officer, told ApexOnco that the unconfirmed responses could still become confirmed. He added that the company is aiming for a response rate of 60-65%, and Zai will now need to show this in more patients.

There was also an interstitial lung disease death in a fourth-line patient receiving of zoci-P at 2.4mg/kg. When asked about the project’s therapeutic window, Amado conceded that this might be narrow.

Still, he maintained that zoci-P could have key advantages, including easier administration. Imdelltra is “difficult to give in an outpatient setting” because of its side effects, Dr Alex Spira of Virginia Cancer Specialists Research Institute said during Zai’s call.

But Amgen’s Chang highlighted that Dellphi-304 shifted from monitoring patients for 48 hours in hospital, to outpatient monitoring over six to eight hours.

Zai plans to start its registrational trial in the second half, testing zoci-P against investigator’s choice of therapy in second-line SCLC, in around 400-500 patients, a spokesperson for Zai told ApexOnco. The proposed dose is 1.6mg/kg, pending FDA agreement, and primary endpoints will be overall survival, to support full approval, and ORR, to support accelerated approval.

Zai believes that an accelerated nod could come in 2027, but it will have to hope that Imdelltra doesn’t put a spanner in the works.

This story has been updated to include further comments from Zai Lab.