Affimed needs more time with AFM24

Affimed impressed at ASCO with its EGFR-targeting NK-cell engager AFM24, but reality kicked in today. An update from the AFM24-102 trial of a Tecentriq combo in heavily pretreated NSCLC showed dwindling response rates, and the company leaned heavily on a post-hoc analysis focusing on patients with high exposure to AFM24.

Despite claiming that current numbers were “competitive”, Affimed will now test a higher dose to try and boost efficacy. But it could be running out of time, with only enough cash to get it to the end of 2025, and no partner in place. The group’s stock sank as much as 30% on Tuesday morning.

Confirmed vs unconfirmed

The AFM24-102 trial enrolled two cohorts: EGFR wild-type patients (all of whom had received prior PD-(L)1 therapy), and EGFR mutants. 

In EGFRwt patients Affimed claimed an overall response rate of 21% – a dropoff from the 27% reported at ASCO. But this latest figure included an unconfirmed response; excluding this the ORR dropped to 18%. 

And this is before taking into account six patients who were excluded from the efficacy-evaluable population because of having early progressive disease. Two more were excluded for discontinuing owing to non-related adverse events, while two patients were ongoing, with no scan yet.

During a conference call on Tuesday Affimed’s chief medical officer, Andreas Harstrick, said that excluding such patients wasn’t unusual for early, uncontrolled trials, but it’s another reason to be cautious about the results.

Evolving data from the AFM24-102 trial of AFM24 + Tecentriq in relapsed NSCLC

Note: *all pts previously received PD-(L)1 inhibitors; **another PR remains unconfirmed. Source: company presentation.

Response rates also slipped in the EGFRm cohort, where all patients had received a prior tyrosine kinase inhibitor, but only 12% had got prior checkpoint inhibitor therapy. In this arm four patients were excluded because of early progressive disease, among 11 exclusions.

Overall, Affimed execs said the data compared well against historical results with docetaxel alone, which is linked with a response rate of around 10% and PFS of around four months.

However, Affimed wants to achieve an ORR of over 30%, and median PFS of over seven months – and believes that it can do this with higher dosing.

The group’s post-hoc analysis divided patients receiving a 480mg weekly dose into those with high or low exposure to AFM24, based on mean trough PK values. In the “high exposure” cohort, Affimed claimed an ORR of 46% and a median PFS of 7.4 months (versus 8% and 1.9 months respectively in the "low exposure" group). However, being post-hoc, these numbers will have to be confirmed prospectively.

The company said the next step would be to enrol a new cohort of AFM24-102, testing Tecentriq plus AFM24 at 720mg/week. Recruitment could start in the first quarter of 2025, and up to 34 patients could be treated, with data expected in the first half of 2026.

Affimed also has the option to open two triplet cohorts, adding either the anti-VEGF MAb Cyramza or docetaxel – these arms could readout in late 2026 or early 2027.

The company will then decide which regimen to take forward into a registration-enabling, randomised, controlled trial. A big question now, with cash running short, is how Affimed will keep going until then.

When asked about potential partnerships the company’s chief executive, Shawn Leland, claimed to have seen increased interest, especially following data at ASH with its anti-CD123 NK cell engager AFM28 (which was marred by a death). Unless a deal emerges, investors will likely continue to be sceptical.