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ADXS-PSA plus Pembrolizumab in metastatic castration-resistant prostate cancer: KEYNOTE-046


ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy that targets prostate-specific antigen ( PSA ), is designed to generate antigen-specific T cell effectors that kill tumor cells.
Published data has shown synergy of ADXS Lm-LLO-TAA treatment with a PD-1 blocking antibody in an animal model.

A phase 1/2 trial studied patients with progressive metastatic castration-resistant prostate cancer ( mCRPC ), greater than or equal to 18 yrs who received 2 or less prior chemo-/targeted-/immunotherapies or 1 or less prior chemotherapy in a metastatic setting.

Part A ( PA; n=14 ) patients received ADXS-PSA doses 1x109; 5 x109 and 1x1010 colony forming units ( CFU ) IV ( intravenous ) every 3 weeks and Part B ( PB; n = 37 ) patients received 1x109 CFU + 200 mg Pembrolizumab IV every 3 weeks with a 4th Pembrolizumab dose 3 weeks later, for up to 2 years or until progression / toxicity.

The first endpoint was safety / tolerability. Anti-tumor activity and effect on PSA level were evaluated.

Preliminary results were presented.

At entry, PA and PB patients were similar in age ( approximately 70 years ), Gleason score ( approximately 8.3 ) and prior Abiraterone use.

PB patients had higher median basaline PSA ( 40.6 v 20.8 ng/ml ), and more prior Enzalutamide ( 53 v 26% ) and chemotherapy ( 49 v 36% ) use versus PA.

46 patients ( 94% ) experienced treatment-related adverse reactions ( TRAE ) with 16 patients having grade 3-4 events: fatigue, hypotension, hypertension, anemia.
TRAEs greater than or equal to 10% of any grade were cytokine release symptoms including chills, fever, nausea and hypotension.
TRAE incidence was similar between groups and all resolved with supportive care.

Overall, 2 PA ( 14% ) v 16 PB pts ( 43% ) had a decreased PSA post-baseline. Of these, 8 PB ( 22% ) versus 0 PA patients achieved a PSA reduction greater than or equal to 50% from baseline; which was confirmed in 3 PB patients ( 38% ).

At the time of analysis, tumor measurements were available for 5 PA and 23 PB patients. One PA patient ( 20% ) and 10 PB patients ( 43% ) had stable disease ( SD ) ( RECIST 1.1 ).
Four PB patients ( 40% ) with stable disease also had a decreased PSA post-baseline; a confirmed response was seen in 2 of these patients.

9 PA and 14 PB patients had non-measurable disease at baseline; 33% ( 3/9 ) and 79% ( 11/14 ) had disease stabilization ( non-CR / non-PD ).

In this population of heavily pretreated mCRPC patients ADXS-PSA plus Pembrolizumab had a manageable safety profile and showed promising activity compared to monotherapy. ( Xagena )

Source: American Society of Clinical Oncology - ASCO Meeting, 2018

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