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
Rinvoq, an oral JAK inhibitor for the treatment of moderate to severe rheumatoid arthritis, approved by FDA
The FDA ( U.S. Food and Drug Administration ) has approved Rinvoq ( Upadacitinib ), a 15 mg, once-daily oral...
Inrebic for patients with intermediate-2 or high-risk primary or secondary myelofibrosis, approved by FDA
The FDA ( Food and Drug Administration ) has approved Inrebic ( Fedratinib ) for adults with intermediate-2 or high-risk...
The FDA ( Food and Drug Administration ) has granted accelerated approval to Xpovio ( Selinexor ) in combination with...
Relapsed and refractory multiple myeloma: European Commission has approved Empliciti plus Pomalidomide and low-dose Dexamethasone
The European Commission ( EC ) has approved Empliciti ( Elotuzumab ) plus Pomalidomide and low-dose Dexamethasone ( EPd )...
Xospata as a monotherapy for patients with relapsed or refractory acute myeloid leukemia with a FLT3 mutation, approved in European Union
The European Commission ( EC ) has approved the oral once-daily therapy Xospata ( Gilteritinib ) as a monotherapy for...
Long-term efficacy and safety of first-line Ibrutinib treatment for patients with chronic lymphocytic leukemia / small lymphocytic lymphoma: 5 years of follow-up from RESONATE-2 trial
RESONATE-2 is a phase 3 study of first-line Ibrutinib ( Imbruvica ) versus Chlorambucil in chronic lymphocytic leukemia ( CLL...
FDA: Reblozyl for the treatment of anemia in adult patients with beta-thalassemia who require regular RBC transfusions
The FDA ( U.S. Food and Drug Administration ) has granted approval to Reblozyl ( Luspatercept–aamt; Luspatercept ) for the...
The FDA ( Food and Drug Administration ) has granted accelerated approval to Polatuzumab vedotin-piiq ( Polivy; Polatuzumab vedotin ),...
DRIVE PK Study in patients with pyruvate kinase deficiency: data for Mitapivat from Core and Extension phases
New data from the core and extension phases of the DRIVE PK phase 2 study of Mitapivat ( AG-348 )...
Cablivi, the first nanobody-based medicine, for adults with acquired thrombotic thrombocytopenic purpura, approved by FDA
The FDA ( U.S. Food and Drug Administration ) has approved Cablivi ( Caplacizumab-yhdp ) in combination with plasma exchange...