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
European Union: Lynparza approved for the treatment of BRCA-mutated metastatic castration-resistant prostate cancer
Lynparza ( Olaparib ) has been approved in the European Union ( EU ) for patients with metastatic castration-resistant prostate...
Cabozantinib in combination with Atezolizumab in patients with metastatic castration-resistant prostate cancer: results of cohort 6 of the COSMIC-021 trial
Cabozantinib ( Cabometyx ) may enhance response to immune checkpoint inhibitors ( ICIs ) by promoting an immune-permissive microenvironment and...
Apalutamide versus placebo in patients with nonmetastatic castration-resistant prostate cancer: final survival results from SPARTAN, a phase III trial
SPARTAN has evaluated Apalutamide ( Erleada ) versus placebo in patients with nonmetastatic castration-resistant prostate cancer ( nmCRPC ) and...
IPATential150 study: Ipatasertib in combination with Abiraterone and Prednisone / Prednisolone met its co-primary endpoint of radiographic progression free survival in patients with PTEN loss tumours
Tthe phase III IPATential150 study met its co-primary endpoint of radiographic progression-free survival ( rPFS ) in patients with metastatic...
Olaparib in combination with Abiraterone delays disease progression in metastatic castration-resistant prostate cancer
Data, presented at 2018 American Society of Clinical Oncology ( ASCO ) Annual Meeting, showed clinical improvement in median radiologic...
IMAAGEN study: effect of Abiraterone and Prednisone on PSA and radiographic disease progression in patients with nonmetastatic castration resistant prostate cancer
Researchers have evaluated the use of Abiraterone acetate ( Zytiga ) ( 1,000 mg ) plus Prednisone ( 5 mg...
Abiraterone acetate provides significant clinical benefit in patients with high-risk metastatic hormone-naïve prostate cancer, improving overall survival and radiographic progression-free survival
Data from the pivotal phase 3 LATITUDE clinical trial showed Abiraterone acetate ( Zytiga ) plus Prednisone, in combination with...
STAMPEDE is a multigroup, multistage platform trial protocol investigating the efficacy of additional therapy at the time of inception of...
Improved cancer-specific free survival and overall free survival in contemporary metastatic prostate cancer patients
Over the past decade, several systemic agents as Docetaxel, Cabazitaxel, Sipuleucel-T, Abiraterone and Enzalutamide have improved overall survival ( OS...