AACR 2022 – Affimed shows that 2021 was no fluke

An academic-sponsored trial gives Affimed’s NK cell engaging approach a huge endorsement.

A year after stealing the show with clinical case reports that were not formally part of AACR, Affimed has unveiled a bigger dataset confirming that this had been no mirage. 19 lymphoma patients are now evaluable in a phase 1 trial, and AFM13 has put 17 of them into remission, this year’s AACR heard today.

True, there are important caveats: the single-site, academic-sponsored trial likely lacks the objective rigour of a multicentre, company-backed study, and Affimed’s own approach with AFM13 is somewhat different. But the group will no doubt benefit as the data endorse NK cell engagement, an approach to which it had pivoted in 2019.

The excitement started during AACR 2021, when during a general talk MD Anderson’s Dr Katy Rezvani described four remissions in the first four Hodgkin’s lymphoma subjects treated with AFM13 plus allogeneic NK cells. Last month Affimed said this trial had now given 13 patients one cycle of the highest NK cell dose (100 million per kg), and the ORR was still 100%, including five complete remissions.

Deepening responses

The latest cut, presented by MD Anderson’s Dr Yago Nieto at an AACR clinical trials plenary today, includes 19 evaluable patients, all now having completed both planned cycles. Not only are all 13 high-dose subjects still in remission, but responses have deepened, and four of six patients on the two lower NK cell doses have also gone into remission.

Among high-dose patients the number of complete responses has increased from five to eight after the second cycle, and the CR rate across all doses is 53%. With the caveat of relatively short follow-up (median 11 months) 53% of patients are progression-free, and 79% are still alive. Importantly, there was only one serious adverse event, a grade 3 infusion-related reaction, and no cytokine release, neurotoxicity or graft versus host.

AFM13 is a bispecific MAb targeting CD30 and CD16A, thus acting as a bridge not with T but with NK cells. MD Anderson’s phase 1 study is in patients with CD30-positive Hodgkin disease or T-cell lymphoma, relapsed after a median six therapies including Seagen’s Adcetris and, in most cases, anti-PD-1 therapy.

Investors will clearly welcome such strong, albeit early, data, but should also note that Affimed’s own registrational phase 2 trial, Redirect, gives only AFM13, relying on it binding with the patient’s endogenous NK cells. The MD Anderson trial is different in that it also includes allogeneic cord blood-derived NK cells, which are activated, expanded and combined with AFM13 before being infused into the patient.

It might be that such a complex manufacturing procedure is unviable commercially, and the big question is whether AFM13 on its own can be efficacious.

Next big test

Affimed will find out soon enough: enrolment into Redirect was completed last year, and the company has promised topline data in the second half of 2022.

It says the trial had a two-year recruitment period, and follow-up will depend on the duration of responses, but the aim is to generate a dataset sufficiently strong for accelerated approval. It has pointed to the HDAC inhibitors Zolinza and Beleodaq, which secured approvals in T-cell lymphoma on the strength of 26-30% ORRs with eight to 10-month duration of response, saying this was “kind of a floor” for the Redirect trial.

Affimed used to develop T cell-recruiting bispecifics, but as this became a hugely competitive area it pivoted to NK-cell engagers like AFM13. It has just seen another big endorsement of this decision, but in readout of the Redirect trial an even bigger test awaits.

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