AP-144™ Autologous NK Cells

AP-144™ Autologous NK Cell Therapy

AP-144™ is an autologous NK cell therapy that activates the patient’s own NK cells to target cancers expressing membrane Hsp70 (“mHsp70”), a cancer-specific biomarker which is highly expressed on aggressive cancer cells, but not on non-cancerous cells.

AP-144™ is manufactured by obtaining a patient’s peripheral blood mononuclear cells (“PBMCs”) by leukapheresis in an out-patient setting, from which NK cells are expanded and cryopreserved. After thawing, NK cells are ex vivo activated using a patented Hsp70-derived synthetic peptide (named “TKD”) and low-dose interleukin-2 (“IL-2”) before being given back to the patient on four occasions.

Planned Phase I/IIa Clinical Combination trial Patients with advanced (Stage IV) NSCLC will receive AP-144™ plus pembrolizumab immune checkpoint inhibitor standard of care. If the clinical trial shows the therapy is effective, a Pivotal Phase IIb trial will be planned for accelerated approval.

The ‘first-generation’ version this autologous membrane Hsp70 targeted NK cell therapy which did not include NK cell expansion (‘ENKASTIM™’), has been evaluated in two clinical trials in Germany.

 

Completed Phase I clinical trial
Involved twelve (12) patients in Germany, eleven (11) with metastatic colorectal cancer and one (1) with non small lung cancer (NSCLC) receiving ENKASTIM™ after standard of care (SOC). The therapy showed it was safe, well tolerated and had signs of efficacy.

 

Completed Phase IIa (randomized, controlled) clinical trial 
Involved fourteen (14) patients with advanced (Stage IIIb) NSCLC in Germany. Of the seven (7) patients who received  ENKASTIM™ after radio-chemotherapy, five (5) patients experienced a clinical benefit (71%), including one complete response (CR) and one partial response (PR). The median Progression Free Survival (PFS) was 13 months, including one patient who left the trial with a PFS of 15 months.

 

In contrast, of the seven (7) patients who received standard of care radio-chemotherapy alone, only two had a clinical benefit (CBR 28%) and a PFS of 8 months. No patient had a CR.

 

A pre-IND meeting to discuss the extension of these studies with the USA FDA was successfully held in September 2021.


Clinical Case Study 58-year-old male patient with Stage IIIb inoperable NSCLC received 2nd line PD1 Inhibitor OPDIVO® (Nivolumab) 3 cycles only, after First Generation ENKASTIMTM, following RCT, demonstrated long-term disease control* No tumor progression nor distant metastases were detectable by CT scan for 33 months after diagnosis. Therapy response was associated with significantly increased NK cell counts, elevated CD8+ to CD4+ T cells.

In contrast, as an historic control, recent clinical trial of unresectable Stage III NSCLC showed PD-1 inhibition OPDIVO® (nivolumab) with concurrent median PFS was 12.7 months.**

1 Krause SW, Gastpar R, Andreesen R, Gross C, Ullrich H, Thonigs G, et al. Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: A clinical phase I trial. Clin Cancer Res (2004) 10:3699-3707.

2 Multhoff G, Seier S, Stangl S, Sievert W, Shevtsov M, Werner C, et al. Targeted natural killer cell based adoptive immunotherapy for the treatment of patients with NSCLC after radiochemotherapy – a randomized phase II clinical study. Clinical Cancer Research (2020) 26:5368-5379. doi:10.1158/1078-0432.CCR-20-1141

 3 Kokowski K, Stangl S, Seier S, Hildebrandt M, Vaupel P, Multhoff G. Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study. Strahlenther Onkol (2019) 195(4):352-361. doi: 10.1007/s00066-019-01434-9.