103 P10-1 open-label, multicenter study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) previously treated with sipuleucel-T: Evaluation of antigen-presenting cell (APC) activation and cellular immune response data

2013 ◽  
Vol 12 (1) ◽  
pp. e103-e104
Author(s):  
T.M. Beer ◽  
J. Corman ◽  
R. Sims ◽  
Y. Wang ◽  
C. De La Rosa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Immune Response ◽  
Multicenter Study ◽  
Open Label ◽  
Response Data ◽  
Castrate Resistant Prostate Cancer ◽  
Previously Treated ◽  
Castrate Resistant ◽  
Cellular Immune ◽  
Antigen Presenting

Open-label, multicenter study of sipuleucel-T in men with metastatic castrate-resistant prostate cancer (mCRPC) previously treated with sipuleucel-T: Evaluation of antigen presenting cell (APC) activation and ELISPOT data.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5053-5053
Author(s):  
Tomasz M. Beer ◽  
L. Michael Glode ◽  
Raymond S. Lance ◽  
Richard H. Greengold ◽  
Corazon P. dela Rosa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostatic Acid Phosphatase ◽  
Cellular Immunotherapy ◽  
Long Term Memory ◽  
Open Label ◽  
Gm Csf ◽  
Castrate Resistant Prostate Cancer ◽  
Previously Treated ◽  
Castrate Resistant ◽  
Antigen Presenting

5053^ Background: P10-1 (NCT01338012) is a study of sipuleucel-T, an autologous cellular immunotherapy, in men with mCRPC previously treated with sipuleucel-T in PROTECT (NCT00779402). This preliminary analysis of P10-1 evaluates APC activation (a measure of product potency) and immune responses in men retreated with sipuleucelET. Methods: Men who received ≥1 infusion of sipuleucel-T in PROTECT and progressed to mCRPC were retreated with 3 infusions of sipuleucel-T. APC activation was assessed by CD54 upregulation. T cell responses to prostatic acid phosphatase (PAP) and PA2024 (PAP-GM-CSF) antigens were assessed by IFN-γELISPOT assay. Results: As of October 23, 2012, 7 men were enrolled and received ≥1 infusion. Median time between the third PROTECT infusion and first P10-1 infusion was 9.2 (range: 7.8–10.0) years. APC activation was greater at the first P10-1 treatment vs the last PROTECT treatment (Table). PA2024 and PAP ELISPOT responses were present prior to retreatment, indicating long-term memory (Table 1); based on other studies of sipuleucel-T, ELISPOT responses are not generally present prior to the first treatment (Beer. Clin Cancer Res 2011; Sheikh. Cancer Immunol Immunother 2013). Conclusions: This is the first trial to report the feasibility of sipuleucel-T retreatment following treatment in an earlier stage of prostate cancer. These data indicate the presence of existing immunological memory to the immunizing antigen several years after initial treatment. In addition, retreatment with sipuleucel-T appeared to boost product potency compared with prior treatment. Clinical trial information: NCT01338012. [Table: see text]

P10-1 open-label, multicenter study of sipuleucel-T in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) previously treated with sipuleucel-T: Evaluation of antigen-presenting cell (APC) activation.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 147-147
Author(s):  
Tomasz M. Beer ◽  
L. Michael Glode ◽  
Raymond Lance ◽  
Richard Greengold ◽  
Robert Brownell Sims ◽  
...  
Keyword(s):  
Multicenter Study ◽  
Specific Antigen ◽  
Phase Iii ◽  
Cellular Immunotherapy ◽  
Open Label ◽  
Culture Cells ◽  
Castrate Resistant Prostate Cancer ◽  
Previously Treated ◽  
Castrate Resistant ◽  
Improvement In Survival

147 Background: Sipuleucel-T is an autologous cellular immunotherapy that has demonstrated an improvement in survival among men with asymptomatic or minimally symptomatic mCRPC. P10-1 (NCT01338012) is an open-label, multicenter study of sipuleucel-T in men with mCRPC previously treated with sipuleucel-T in the androgen-dependent setting on the PROTECT trial (a prospective, randomized, controlled Phase III study of sipuleucel-T in men with prostate-specific antigen recurrence following radical prostatectomy; NCT00779402). This preliminary analysis of P10-1 evaluates the pattern of APC activation in pts re-treated with sipuleucel-T after progression to mCRPC. Methods: Eligible pts include those previously treated with at least one infusion of sipuleucel-T on PROTECT and who progressed to the mCRPC state. Pts receive up to three additional infusions of sipuleucel-T. APC activation is assessed by CD54 upregulation expressed as the ratio of the average number of CD54 molecules on post-culture vs. pre-culture cells. Results: As of September 14, 2012, 7 pts have been enrolled and have received an infusion of sipuleucel-T. The median interval between the last infusion in PROTECT and the first infusion in P10-1 was 8.6 years. The Table shows a higher fold change in CD54 expression in the first P10-1 treatment compared with the initial infusion in PROTECT. Conclusions: This is the first report of pts re-treated with sipuleucel-T after prior treatment in an earlier disease setting. These preliminary data are consistent with the presence of an immunological memory response to the immunizing antigen several years following initial treatment. Clinical trial information: NCT01338012. [Table: see text]

Patient-reported outcomes with metastatic castrate-resistant prostate cancer.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 207-207
Author(s):  
Jimmy Mullally ◽  
Christopher Davella ◽  
Rahul Atul Parikh ◽  
G J. Van Londen ◽  
Leonard Joseph Appleman
Keyword(s):  
Prostate Cancer ◽  
Cognitive Impairment ◽  
Disease Progression ◽  
Well Being ◽  
Open Label ◽  
Hormonal Function ◽  
Patient Reported ◽  
Data Points ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

207 Background: Prostate cancer accounts for approximately 10% of cancer deaths in men worldwide. Clinical trials for metastatic castrate resistant prostate cancer (mCRPC) have established survival benefit with use of abiraterone (ABI) with prednisone or enzalutamide (ENZ). Despite their wide utilization, little is known about patient quality-of-life (QOL) outcomes for these agents. Our study evaluates patient reported QOL while taking ENZ or ABI/prednisone. Methods: 22 mCRPC patients were enrolled in an open label, nonrandomized manner to receive oral ENZ (n=12) or ABI/prednisone (n=6) per oncologist’s discretion. Patients completed multiple QOL validated questionnaires, including EPIC-26, FACT-P, and FACT-COG at baseline, 1,2,3,6,9 and 12 months or until progression/change of therapy. Surveys were scored by treatment group using mean, median, range, and standard deviations. QOL parameters were compared between the two groups with two-sided, two-sample T test and linear mixed models. Results: Surveys discontinued prior to 1 year secondary to disease progression/change of therapy were 58% and 33% for ENZ and ABI, respectively. By month 3, 50% of surveys were returned for ENZ and 33% for ABI. Month-to-month comparisons of QOL parameters including urinary irritation, incontinence, bowel, sexual, hormonal function, and overall well-being showed no significant differences between treatment groups or different rates of change. Perceived Cognitive Impairment was significantly lower for patients on ABI in month 3, yet Perceived Cognitive Ability favored ENZ in months 2 and 3. All other data points for cognition showed no significant differences. Conclusions: Data from FACT-COG shows discordance in perceived Cognitive Impairment and Abilities between ENZ and ABI in months 2-3. Other QOL domains indicated no difference between the two groups. The study was limited by a significant portion of patients with disease progression/change of therapy. For those on therapy, survey compliance remained high. Thus, the use of questionnaires is a feasible means of assessing patient outcomes and can be adapted to larger studies.

A randomized phase II trial of sipuleucel-T with concurrent or sequential abiraterone acetate (AA) plus prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5047-5047 ◽  
Author(s):  
Eric Jay Small ◽  
Raymond S. Lance ◽  
Charles H. Redfern ◽  
Frederick E. Millard ◽  
Thomas A. Gardner ◽  
...  
Keyword(s):  
Immune Responses ◽  
Similar Efficacy ◽  
Abiraterone Acetate ◽  
Cellular Immune Responses ◽  
Randomized Phase Ii ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Cellular Immune ◽  
Antigen Presenting ◽  
Clinical Trial Information

5047^ Background: Sipuleucel-T and AA + P are FDA-approved for asymptomatic/minimally symptomatic mCRPC. Suppression of the androgen axis can be immunostimulatory and AA suppresses circulating androgen levels; AA plus sipuleucel-T may therefore be synergistic. However P used with AA, which may be immunosuppressive, has not been studied with concurrent sipuleucelET and could impair sipuleucel-T production and/or immunologic response. P11-3 (NCT01487863) is the 1st study to evaluate the combination of sipuleucel-T and AA + P Methods: Patients (pts) with asymptomatic/minimally symptomatic mCRPC were randomized (1:1) to sipuleucel-T (3 infusions at approx 2-wk intervals) with up to 26 wks of AA + P (AA 1000mg QD + P 5mg BID) starting 1 day after the 1st sipuleucel-T infusion (concurrent, arm A) or at 10 wks following the 1st sipuleucel-T infusion (sequential, arm B). Endpoints included the effect of AA + P on product (sipuleucel-T) characteristics eg antigen presenting cell (APC) activation, measured as CD54 upregulation (primary endpoint), APC (measured as CD54+ cells) and total nucleated cell (TNC) counts, as well as safety and immunologic responses. Results: 31 pts in arm A and 32 pts in arm B completed sipuleucel-T treatment by the interim analysis (Nov 2012). Baseline characteristics were similar in the 2 arms. 60/63 pts received all 3 infusions of sipuleucel-T. No significant differences in median cumulative APC activation, APC count or TNC count were seen between the arms. Increased CD54 upregulation with the 2nd and 3rd treatments were indicative of a prime boost effect in both arms. Similar profiles of antigen-specific humoral and cellular immune responses were generated with no difference in magnitude of response between the arms (p>0.05). The incidence of adverse events (AEs) and serious AEs was similar in both arms. Conclusions: These data suggest sipuleucel-T can be successfully manufactured during concurrent AA + P. Product potency and prime boost effect were similar to sipuleucel-T alone. Immune responses and AEs were similar in both arms. It is not known if sipuleucel-T will provide similar efficacy with concurrent or sequential AA + P. Clinical trial information: NCT01487863.

TNB585.001: A multicenter, phase 1, open-label, dose-escalation and expansion study of tnb-585, a bispecific T-cell engager targeting PSMA in subjects with metastatic castrate resistant prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS5092-TPS5092
Author(s):  
Ben Buelow ◽  
Pranjali Dalvi ◽  
Kevin Dang ◽  
Ashwin Patel ◽  
Kiran Johal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cell ◽  
Dose Escalation ◽  
Phase 1 ◽  
Specific Antigen ◽  
Outpatient Basis ◽  
Open Label ◽  
Psma Pet ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

TPS5092 Background: Prostate cancer (CaP) is the most common cancer in US men. Disseminated CaP invariably progresses to metastatic castrate-resistant prostate cancer (mCRPC). Current treatment options for mCRPC usually lead to therapeutic resistance, and novel therapies are urgently needed. PSMA is a prostate-specific antigen over-expressed on most mCRPC. Antibodies against PSMA have been used to create T-cell engaging bispecific Abs (TCEs) and chimeric antigen receptor T cells, but all such approaches to date induce frequent/severe cytokine release syndrome (CRS). We combined a high-affinity αPSMA moiety with a low-activating αCD3 binder to create TNB-585; in preclinical studies, TNB-585 showed equivalent anti-tumor efficacy but much reduced cytokine secretion compared to PSMA-targeted TCEs with a strongly activating αCD3 domain. TNB-585 also has a full length silenced Fc domain, conferring a 3-week half-life. A phase 1 study investigating the safety, pharmacokinetics (PK), anti-drug antibodies (ADA) and preliminary activity of TNB-585 in patients with mCRPC is ongoing and described. Methods: TNB585.001 (NCT04740034) is an open-label, multi-center study of TNB-585 in patients with mCRPC. The study is divided into escalation (Arm A, N=24) and expansion (Arm B, N=30) arms. Subjects who have received 2 or more prior lines of therapy are eligible. Prior exposure to PSMA-targeted therapy is permitted, as are well-controlled HBV, HCV, and HIV infection; subjects with secondary malignancies that do not interfere with the study may also be enrolled. Other key inclusion/exclusion criteria include EGFR of > 30ml/min and ECOG ≤ 2. TNB-585 is administered as an intravenous infusion every 3 weeks. Subjects must be admitted for 48 hours after their 1st dose; TNB-585 is given on an outpatient basis thereafter. Dose escalation is proceeding in Arm A via single patient cohorts until the onset of toxicity or activity; thereafter subjects enroll using a BOIN design. Arm B will start once the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) has been selected. Subjects will be treated until progression or unacceptable toxicity. In Arm A, occurrence of dose limiting toxicities (DLTs) will drive identification of the MTD (or RP2D) based on the BOIN escalation and de-escalation boundaries (λe of 0.236 and a λd of 0.358). In Arm B accrual will be suspended if more than 33% of subjects experience a DLT event. Adverse events (AEs), laboratory profiles, and vital signs will be assessed throughout the study. AEs are graded according to the NCI CTCAE, version 5.0. The activity endpoints (per PCWG3/RECIST1.1) include overall response rate, PSA50, PSA30, CTC counts, progression free survival and overall survival. The relationship between PSMA expression (via PSMA-PET) and activity will be assessed. Clinical trial information: NCT04740034.

scholarly journals An Open-Label, Multicenter, Phase I/II Study of Single-Agent AT-101 in Men with Castrate-Resistant Prostate Cancer

2009 ◽  
Vol 15 (9) ◽  
pp. 3172-3176 ◽  
Author(s):  
Glenn Liu ◽  
W. Kevin Kelly ◽  
George Wilding ◽  
Lance Leopold ◽  
Kimberli Brill ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Single Agent ◽  
Open Label ◽  
Multicenter Phase ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant
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