Daiichi Sankyo and Merck & Co’s fast move into phase 3 with ifinatamab deruxtecan just got some more clinical backing. A presentation at World Lung’s presidential session of the results of the Ideate-Lung01 trial, in relapsed small-cell lung cancer, support data from the small cohort of a multi-tumour basket trial that until now was the only sign of this molecule’s efficacy in SCLC.
Specifically the phase 2 Ideate-Lung01 results also show clearly why it was the 12mg/kg dose that the companies have taken into phase 3. While the basket trial tested four different doses Ideate-Lung01 zeroed in on 8mg/kg and 12mg/kg, and it was the latter that has clearly come out on top.
The finding broadly mirrors the basket trial data, where ifinatamab-dxd 12mg/kg did best. This left open the question of even higher dosing, as only one patient received 16mg/kg and developed a partial response, but safety is key; given the Daiichi payload’s association with interstitial lung disease (ILD), once acceptable efficacy has been seen there’s little point risking higher doses.
Clearly any toxicity signals will loom large over Ideate-Lung02, the pivotal SCLC study Daiichi/Merck began in May.
Among Ideate-Lung01’s 88 patients, meanwhile, the World Conference on Lung Cancer heard of nine treatment-emergent AEs that resulted in death; none of the three with 8mg/kg was deemed treatment related, while one of the six (Pneumocystis jirovecii pneumonia) in the 12mg/kg group was; one case of ILD, at grade 2, caused treatment discontinuation in the 12mg/kg cohort.
Phase 2 efficacy
As for efficacy, Ideate-Lung01 yielded ORRs of 26% for ifinatamab-dxd at 8mg/kg, and a much more impressive 55% for 12mg/kg. The latter is more in line with the response data seen in the basket trial, and importantly it’s higher than the 35% ORR (or 45% in patients with a chemo-free interval over 90 days) cited on the label of PharmaMar/Jazz’s Zepzelca in a broadly similar SCLC population.
This cross-trial comparison is important because Zepzelca features among the treatment choices in the control cohort of ifinatamab-dxd’s pivotal Ideate-Lung02 trial. That study lists ORR as well as overall survival as co-primary endpoints.
And Ideate-Lung01 has already shown survival numbers: ifinatamab-dxd 12mg/kg yielded 11.8 months of median OS, which again looks impressive on a cross-trial basis; Zepzelca’s label doesn’t cite any OS figures, but one investigator-sponsored trial of the drug’s real-world use under a French early-access programme found median OS to be just 4.7 months, a 2023 ASCO poster showed.
Ifinatamab-dxd is an ADC targeting B7-H3, a modality in which interest has been building since Merck gained rights to the Daiichi molecule in last year’s monster ADC deal. Also closely watched is Hansoh Pharma/GSK’s HS-20093, but MacroGenics has hit major problems with vobramitamab duocarmazine.
Ifinatamab deruxtecan in SCLC
| Study | Setting | Doses (mg/kg) | Patients | Data |
|---|
| Ph1/2 basket trial | Median 3rd-line (1-7 prior treatments) | 6.4, 8.0, 12.0 & 16.0 | 21 | 1 CR & 10 PRs | ORR=53% |
| Ph2 Ideate-Lung01 | 2nd to 4th-line | 8.0 & 12.0 | 88 | 1 CR & 11 PRs for 8.0mg/kg;
23 PRs for 12.0mg/kg | ORR=26% for 8.0mg/kg
ORR=55% for 12.0mg/kg |
| Ph3 Ideate-Lung02 | 2nd-line (with >30 day chemo-free interval) | 12.0 | 468 | Co-primaries: OS & ORR vs physician’s choice including Zepzelca |
