Trial Will Test AFM24-Tecentriq Combo for EGFR-positive Advanced Cancers

Trial Will Test AFM24-Tecentriq Combo for EGFR-positive Advanced Cancers

Affimed will team up with Roche to conduct a Phase 1/2a clinical trial investigating its innate cell engager AFM24 — a form of immunotherapy — in combination with Tecentriq (atezolizumab) for the treatment of EGFR-positive solid cancers that progressed despite prior therapies.

Under a new collaboration agreement, Affimed will fund and conduct the trial, while Roche will be supplying its immune checkpoint inhibitor Tecentriq.

“This collaboration with Roche is an important step in our continued execution of AFM24’s clinical development strategy,” Adi Hoess, MD, PhD, CEO of Affimed, said in a press release.

Epidermal growth factor (EGF) is a key signaling molecule in cells that plays an important role in the development and progression of multiple solid cancers, including lung, colorectal, and head and neck cancers. While several treatments targeting the EGF receptor (EGFR) have been approved for these cancers, they are often associated with side effects and resistance to treatment, which limit their use.

AFM24 is a form of immunotherapy that acts as a bridge between innate immune cells — the first line of defense against threats — and cancer cells. Called an innate cell engager (ICE), the treatment works by binding to proteins on both cell types, bringing immune cells closer to the tumor site for more effective killing.

Specifically, AFM24 binds to the CD16A surface receptor on the surface of key innate immune cells, namely natural killer (NK) cells and macrophages, and to the EGFR receptor on tumor cells.

In preclinical studies, AFM24 was shown to induce the death of tumor cells irrespective of their EGFR levels, or the presence of mutations that wound render other EGFR-targeting treatment ineffective.  The cell engager also was found to be safe and well-tolerated when administered weekly to non-human primates, with no skin or organ toxicity.

The upcoming Phase 1/2 trial will assess the effectiveness of combining AFM24 with Tecentriq, an antibody-based immunotherapy that blocks PD-L1, a protein produced by cancer cells to evade the immune system.

The combination of both therapies is expected to boost the body’s immune response — both the innate and adaptive responses — against tumors. The trial will assess and establish the best dose regimen for the combo therapy, as well as its safety and effectiveness.

“Preclinical and clinical studies indicate that ICE and PD-L1 checkpoint inhibition therapy could act synergistically, which drives our optimism about the combination of AFM24 with atezolizumab and its promise as a possible treatment option for patients with EGFR expressing solid tumors,” Hoess said.

Affimed also is investigating AFM24 as a single agent in a Phase 1/2 trial (NCT04259450) for people with advanced EGFR-positive solid tumors who received one or more prior lines of therapy.

That first-in-human, open-label study aims to assess the therapy’s safety, tolerability, and anti-tumor activity in two phases. In the first, dose-escalation part, patients will receive ascending doses of AFM24, delivered weekly via intravenous (into-the-vein) infusions, to establish the maximum tolerated dose and identify the optimal dose for additional testing.

The second part is a dose-expansion phase designed to continue evaluating the optimal dose in an additional group of patients with metastatic colorectal cancer and non-small cell lung cancer.

The study, which is now recruiting in the U.S., the U.K., and Spain, will enroll up to 70 participants and is expected to be completed in March 2023.

“AFM24 is a first-in-class innate cell engager that we believe has the potential to bring benefit to a broad set of patients as monotherapy and in combination with other [immuno-oncology] therapies to address disease states where co-activation of the innate and adaptive immune systems is beneficial,” Hoess said.