Abstract 681P
Background
PROSTVAC (P) is a therapeutic cancer vaccine targeting PSA. Despite a negative trial in advanced disease, BCRpc (rising PSA after surgery (RP)/radiation (RT)) has minimal tumor burden and possibly less associated immune suppression. This study of P evaluated immune responses and changes in PSA kinetics which could delay the morbidity of metastasis.
Methods
Key eligibility criteria include PSA<30, >0.8 after RP, >2.0 after RT, doubling time (DT) 5-15 months (mos), testosterone>100 ng/dl, negative CT and bone scan. Patients (Pts) were randomized to P for 6 mos vs. 6 mos surveillance (S) followed by 6 mos of P. The primary objective evaluated the impact of P on PSA growth rate (G) at 6 months vs. S. PSA DT was also evaluated. In a post hoc analysis delayed PSA declines were identified after an Intra-Study Apex PSA (ISAP; peak PSA affirmed by a contiguous PSA within 10%) to exclude lab variations. Peripheral immune cells were analyzed in 138 subsets by multiparametric flow cytometry.
Results
71 pts are evaluable with a median age and PSA of 66.8 years and 2.98 ng/ml for P and 66.4 years and 2.82 ng/ml for S, respectively. There was no difference in G at 6 mos in the 2 arms. After 6 mos of P 24/71 (34%) had a PSA DT >15 mos vs. 7 (19%) on 6 mos of S (p=0.12). Only 1/37 (3%) pts had a delayed PSA decline from ISAP on S vs. 15/71 (21%) pts treated with P (p=0.0099) with range of decline from ISAP of 10%-99% lasting 55-1420+ days. For the 31 pts on S with a confirmed on-study PSA DT who went on to get P, 6 (20%) had no change in PSA DT (defined as +/- 20%) vs. 16 (53%) who had a >20% increase/improvement in PSA DT (p=0.015). Toxicity was limited grade 1/2. Pts treated with P had increases in natural killer cells (Ki67+ and the activating receptors NKG2D and NKp30) and increases in Ki67+CD4+T cells not seen in S. Pts with delayed PSA declines had higher baseline levels of effector memory CD4+T cells, CD4+T that expressed CTLA4 and PD-L1, and lower levels of classical monocytes expressing PD-1.
Conclusions
Subsets of BCRpc pts treated with P had improvements in PSA DT and late sustained PSA declines compared to S (21% vs. 3%) suggesting potential for immune modulation in BCRpc. Further studies are on-going (NCT03315871).
Clinical trial identification
NCT02649439.
Editorial acknowledgement
Legal entity responsible for the study
National Cancer Institute.
Funding
Bavarian Nordic.
Disclosure
R.A. Madan: Research grant/Funding (institution): Bayer. S. Slovin: Advisory/Consultancy: Clovis; Advisory/Consultancy: Astellas/Pfizer; Advisory/Consultancy: Bayer; Speaker Bureau/Expert testimony: Onc Live; Speaker Bureau/Expert testimony: PER; Speaker Bureau/Expert testimony: Prime Oncology; Speaker Bureau/Expert testimony: SITIC; Research grant/Funding (self): AstraZeneca. L.C. Harshman: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy, Research grant/Funding (self): Dendreon; Advisory/Consultancy, Research grant/Funding (self): Medivation/Astellas; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Kew Group; Advisory/Consultancy: Corvus; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy: Michael J Hennessy Associates ; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Jounce; Advisory/Consultancy: EMD Serrano; Full/Part-time employment: Surface Oncology; Research grant/Funding (self): Jannsen; Research grant/Funding (self): Merck; Research grant/Funding (self): Sotio; Advisory/Consultancy, Research grant/Funding (self): Pfizer. X.X. Wei: Research grant/Funding (self): Bristol Myers Squib. P. Arlen: Leadership role, Shareholder/Stockholder/Stock options: Precision Biologics. A. Hankin: Shareholder/Stockholder/Stock options: amgen; Shareholder/Stockholder/Stock options: medtronic. J. Schlom: Research grant/Funding (institution): Bavarian Nordic. P.W. Kantoff: Advisory/Consultancy, Leadership role, Shareholder/Stockholder/Stock options: Context Therapeutics; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Druggablity Technologies; Shareholder/Stockholder/Stock options: Placon; Shareholder/Stockholder/Stock options: Seer; Advisory/Consultancy: Bavarian Nordic; Advisory/Consultancy: GE Health Care; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: OncoCellMDX; Advisory/Consultancy: Progenity. J.L. Gulley: Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Bristol-Myers Squibb ; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Merck; Research grant/Funding (institution): NantBioScience, Inc. All other authors have declared no conflicts of interest.