AFM13 Showcases 100% ORR in Relapsed/Refractory CD30+ Hodgkin Lymphoma

Katy Rezvani, MD, PhD

AFM13 (CD16A/CD30), an innate cell engager, demonstrated an objective response rate (ORR) of 100% in adult patients with CD30-positive, relapsed/refractory Hodgkin lymphoma, according to early findings from a small phase 1 trial (NCT04074746) that were presented virtually during the AACR Annual Meeting 2021.^1,2

Data showed that the first 4 patients all responded to the therapy, leading to a 100% ORR which comprised 2 complete responses (CRs) and 2 partial responses (PRs). Regarding safety, no cytokine release syndrome, neurotoxicity syndrome, or graft-vs-host disease was observed.

Katy Rezvani, MD, PhD, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center, presented the data as part of the Major Symposia and Advances sessions during the conference.

“There remains a high unmet need for effective treatments in relapsed/refractory CD30-positive lymphomas. We are encouraged by the data generated from the first patients treated with [cord-blood natural killer (cbNK)] cells pre-complexed with AFM13,” Rezvani said in a prepared statement. “The results suggest this combination is facilitating clinical responses with minimal toxicity, warranting further study as we continue to explore novel cell therapies for our patients.”

AFM13 is described as a first-in-class innate cell engager that activates the immune system and targets CD30-positive hematologic cancers; AFM13 induces specific and selective killing of CD30-positive cells. The therapy is also being tested as a single agent in the ongoing, registration-directed REDIRECT study (NCT04101331) in patients with relapsed/refractory peripheral T-cell lymphoma or transformed mycosis fungoides.

In the investigator-sponsored, dose-escalation, phase 1 trial in Hodgkin lymphoma, researchers are exploring AFM13 in combination with cord blood–derived allogeneic natural killer (cbNK) cells in patients with recurrent/refractory CD30-positive lymphomas. Patients are first given cyclophosphamide at 300 mg/m² and fludarabine at 30 mg/m², before receiving AFM13 at one of the following doses: 1 x 10⁶ NK cells/kg (cohort 1), 1 x 10⁷ NK cells/kg (cohort 2), 1 x 10⁸ NK cells/kg in cohort 3.

The primary end point is safety, efficacy, and determine the recommended phase 2 dose. In all cohorts, the dose of pre-complexed NK cells with AFM13 is followed by 200 mg of AFM13 alone for 3 weeks. All patients were evaluated for dose-limiting toxicities and responses on day 28.

As of March 31, 2021, 3 patients were dosed with 2 cycles of therapy in dose cohort 1 (1 x 10⁶ of AFM13-cbNK/kg) and 1 patient received a single cycle of treatment at dose cohort 2 (1 x 10⁷ AFM13-cbNK/kg).

The patient demographics at dose cohort 1 was as follows:

• A 43-year-old male with Hodgkin lymphoma who had underwent 4 lines of treatment (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]; ifosfamide, carboplatin and etoposide [ICE]; brentuximab vedotin [Adcetris], and nivolumab [Opdivo] plus ruxolitinib [Jakafi])
• A 31-year-old male with Hodgkin lymphoma with 14 prior lines of therapy (ABVD, brentuximab vedotin, HDAC inhibitor/PI3K inhibitor, pembrolizumab [Keytruda], nivolumab, allogeneic hematopoietic stem cell transplant [HSCT], hypercytoxan, ibrutinib [Imbruvica], niraparib [Zejula], bendamustine, everolimus [Afinitor])
• A 53-year-old female with Hodgkin lymphoma who previously received 5 lines of therapy (ABVD, ICE, brentuximab vedotin, nivolumab, and gemcitabine/oxaliplatin)

Dose cohort 2, which is ongoing, currently includes a 26-year-old male with Hodgkin lymphoma who underwent 9 lines of treatment (ABVD, ICE and brentuximab vedotin, radiation, nivolumab, CD30-based CAR T-cell therapy, TTI-622, brentuximab vedotin/bendamustine, allogeneic HSCT, brentuximab vedotin/bendamustine with brentuximab vedotin maintenance). Three patients are expected to be enrolled in this cohort overall.

Responses are assessed by the Lymphoma Response to Immunomodulatory Therapy Criteria.

Preclinical findings of this therapy, which Rezvani highlighted in the AACR presentation, showed that interleukin (IL)-12, IL-15, and IL-18 pre-activated and ex-vivo–expanded cbNK cells can develop properties similar to chimeric antigen receptor–like properties when precomplexed with AFM13. Moreover, compared with cells that were only expanded, the IL-12/15/18 pre-activated and ex-vivo–expanded cbNK cells showed upregulation of genes that were related to JAK-STAT signaling and interferon gamma response.

AFM13 was also found to be retained on surface NK cells following pre-complexing, which endows them with CAR-like properties against CD30–positive Karpas 299. Furthermore, AFM13-complexed CAR-like cbNK cells display heightened ability to control tumors in a xenograft mouse model of CD30-positive T-cell lymphoma in vivo.

Currently, the phase 1 study is enrolling patients onto dose cohort 2 with additional data reported later this year.

“We are encouraged by the initial safety and efficacy data from this groundbreaking first-in-human study. The finding of an objective response rate of 100% amongst our first 4 patients enrolled is impressive,” Andreas Harstrick, MD, chief medical officer of Affimed, said in a prepared statement. “These initial results indicate AFM13 may have the potential to help NK cells target and destroy cancer cells. We plan to continue to develop and customize approaches that leverage the unique and differentiating features of our ICE molecules in combination with adoptive NK cell transfer to provide options for treating a variety of hematologic and solid tumors.”

References

1. Affimed announces presentation at AACR highlighting initial data from phase 1 study of cord blood-derived natural killer cells pre-complexed with innate cell engager AFM13. News release. AffiMed. April 9, 2021. Accessed April 12, 2021. https://bit.ly/3wPTJvt.
2. Rezvani K. CAR NK cells: a drive to the future of cell therapy. Presented at: AACR Annual Meeting 2021; April 10-15, 2021; Virtual.