Phase I study of AMG 160, a half-life extended bispecific T-cell engager (HLE BiTE immune therapy) targeting prostate-specific membrane antigen, in patients with metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS5590-TPS5590 ◽  
Author(s):  
Ben Tran ◽  
Lisa Horvath ◽  
Matthew Rettig ◽  
Karim Fizazi ◽  
Martijn P. Lolkema ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Antitumor Activity ◽  
Phase I Study ◽  
Immune Therapy ◽  
Prostate Specific Membrane Antigen ◽  
Pet Ct ◽  
Specific Membrane

TPS5590 Background: Prostate-specific membrane antigen (PSMA) is a clinically validated therapeutic target for the imaging and treatment of mCRPC. AMG 160 is an HLE BiTE immune therapy designed to redirect T cells to cancer cells by binding to PSMA on cancer cells and CD3 on T cells. BiTE immune therapy leads to direct tumor cell killing, T-cell activation and expansion, and the creation of a pro-inflammatory tumor microenvironment. Combining AMG 160 with a PD-1 inhibitor may enhance antitumor activity by enabling sustained T-cell-dependent killing of tumor cells in the inflamed tumor microenvironment. Methods: NCT03792841 is a phase I study of AMG 160 as monotherapy (part 1) and in combination with pembrolizumab (part 2) in men with histologically/cytologically confirmed mCRPC who are refractory to a novel hormonal therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed 1–2 taxane regimens (or are medically unsuitable or have refused taxanes), who have ongoing castration with total serum testosterone ≤ 50 ng/dL, and have evidence of progressive disease. Patients who received prior PSMA radionuclide therapy may be eligible. Patients with CNS metastases, leptomeningeal disease, spinal cord compression, or active autoimmune disease will be excluded. Primary objectives are to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of AMG 160 given as monotherapy or in combination with pembrolizumab. Secondary objectives are to characterize pharmacokinetics and preliminary antitumor activity. Exploratory objectives include evaluation of potential pharmacodynamic and patient selection biomarkers, immunogenicity, and patient-reported pain and functional outcomes. The part 1 dose exploration will determine the MTD/RP2D of AMG 160. The part 1 dose expansion will confirm the safety and tolerability of the MTD/RP2D. The part 2 dose exploration will estimate the MTD/RP2D of AMG 160 in combination with pembrolizumab. Evaluation of preliminary antitumor activity will be based on RECIST 1.1 with Prostate Cancer Working Group 3 modifications, PSA response, CTC response, progression-free survival (radiographic and PSA), and overall survival. PSMA PET/CT and FDG PET/CT imaging will be used for evaluation of exploratory objectives. The study opened in February 2019 and is currently recruiting patients into both part 1 and part 2. Clinical trial information: NCT03792841 .

A phase I/II study of REGN5678 (Anti-PSMAxCD28, a costimulatory bispecific antibody) with cemiplimab (anti–PD-1) in patients with metastatic castration-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. TPS174-TPS174
Author(s):  
Jingsong Zhang ◽  
Mark N. Stein ◽  
William Kevin Kelly ◽  
Che-Kai Tsao ◽  
Gerald Steven Falchook ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
T Cell ◽  
Phase I ◽  
Dose Escalation ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Anti Tumor Activity ◽  
Specific Membrane

TPS174 Background: Bispecific antibodies (bsAbs) are emerging as a protein-based therapeutic strategy for directing T-cell-mediated cytotoxicity in a tumor antigen-specific manner, typically by binding to both tumor antigen and the CD3 receptor on T-cells. REGN5678 is a human IgG4-based, first-in-class costimulatory bsAb designed to target prostate tumors by bridging prostate specific membrane antigen expressing tumor cells with the costimulatory receptor, CD28, on T-cells, and providing amplified T-cell receptor-CD3 complex-mediated T-cell activation within the tumor through the activation of CD28 signaling. At the tumor site, REGN5678 may synergize with PD-1 inhibitors. In mouse models, REGN5678 in combination with a PD-1 antibody has improved anti-tumor activity compared with either therapy alone (Waite JC et al. Sci Transl Med. 2020:12;549). Methods: This is an open label, Phase I/II, first-in-human study evaluating safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of REGN5678 alone and in combination with cemiplimab in patients with metastatic castration resistant prostate cancer (mCRPC) who progressed after prior therapy (NCT03972657). For inclusion, patients must have received at least two prior lines of systemic therapy (in addition to androgen deprivation therapy) approved for metastatic and/or castration-resistant disease including a second-generation anti-androgen therapy. REGN5678 is administered weekly; cemiplimab (350 mg) is administered once every 3 weeks. During dose escalation, a 3-week safety lead-in of REGN5678 monotherapy will be administered prior to addition of cemiplimab. Study therapies are administered until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal criterion is met. The primary objectives in dose escalation are to evaluate safety, tolerability, and PK of REGN5678 alone and in combination with cemiplimab. Expansion cohort(s) will be enrolled once a maximum-tolerated REGN5678/cemiplimab dose is reached, or if a recommended Phase 2 dose or doses have been determined. During the expansion phase, the primary objective is to assess clinical activity, as measured by objective response rate of REGN5678 in combination with cemiplimab per modified Prostate Cancer Working Group 3 criteria. At selected sites, prostate-specific membrane antigen PET/CT scans are performed at baseline and select time points on study. This study is currently open to enrollment. Clinical trial information: NCT03972657.

Head-to-Head Comparison of 18F-Prostate-Specific Membrane Antigen-1007 and 18F-Fluorocholine PET/CT in Biochemically Relapsed Prostate Cancer

2019 ◽  
Vol 44 (12) ◽  
pp. e629-e633 ◽  
Author(s):  
Ewa Witkowska-Patena ◽  
Agnieszka Giżewska ◽  
Mirosław Dziuk ◽  
Jolanta Miśko ◽  
Anna Budzyńska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Membrane Antigen ◽  
Pet Ct ◽  
Specific Membrane

A Comprehensive Safety Evaluation of 68Ga-Labeled Ligand Prostate-Specific Membrane Antigen 11 PET/CT in Prostate Cancer

2017 ◽  
Vol 42 (7) ◽  
pp. 520-524 ◽  
Author(s):  
Julie B. Nielsen ◽  
Helle D. Zacho ◽  
Uwe Haberkorn ◽  
Karin M. Nielsen ◽  
Katja Dettmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Evaluation ◽  
Prostate Specific Membrane Antigen ◽  
Pet Ct ◽  
Specific Membrane

DNA vaccine with pembrolizumab to elicit antitumor responses in patients with metastatic, castration-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 168-168 ◽  
Author(s):  
Douglas G. McNeel ◽  
Jens C. Eickhoff ◽  
Robert Jeraj ◽  
Mary Jane Staab ◽  
Jane Straus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
T Cell ◽  
Dna Vaccine ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Flt Pet ◽  
Pet Ct

168 Background: We have previously investigated a DNA vaccine encoding prostatic acid phosphatase (PAP, pTVG-HP) in patients with PSA-recurrent prostate cancer, and have demonstrated that this can be safely administered over many months and can elicit PAP-specific T cells. A phase 2 trial is currently underway. In preclinical models, we have found that blockade of regulatory receptors, including PD-1, at the time of T cell activation with vaccination produced anti-tumor responses in vivo. Similarly, we have recently found that patients with prostate cancer previously immunized with a DNA vaccine develop PD-1-regulated T cells. These findings suggested that combined PD-1 blockade with vaccination should elicit superior anti-tumor responses in patients with prostate cancer. Methods: A clinical trial was designed to evaluate the immunological and clinical efficacy of pTVG-HP when delivered in combination or in sequence with pembrolizumab, in patients with mCRPC. Serial biopsies, blood draws, and exploratory FLT PET/CT imaging are being conducted for correlative analyses. Results: While trial accrual continues, 1 of 14 subjects has experienced a grade 3 adverse event. There have been no grade 4 events. Several patients treated with the combination have experienced serum PSA declines, and several have experienced decreases in tumor volume by radiographic imaging at 12 weeks, including one partial response. Expansion of PAP-specific Th1-biased T cells has been detected in peripheral blood samples. Exploratory FLT PET/CT imaging has demonstrated proliferative responses in metastatic lesions and in vaccine-draining lymph nodes. Evaluation of biopsy specimens for recruitment of antigen-specific T cells is currently underway. Conclusions: PD-1 pathway inhibitors have demonstrated little clinical activity to date when used as single agents for treating prostate cancer. Our findings suggest that combining this blockade with tumor-targeted T-cell activation by a DNA vaccine is safe and can augment tumor-specific T cells, detectable within the peripheral blood and by imaging, and result in objective anti-tumor changes. Clinical trial information: NCT02499835.

Prostate-specific membrane antigen (PSMA) PET-CT guided radiotherapy in oligometastatic prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 213-213
Author(s):  
Benedikt Engels ◽  
Ozan Cem Guler ◽  
Cem Onal ◽  
Mark De Ridder
Keyword(s):  
Prostate Cancer ◽  
Lymph Nodes ◽  
Pelvic Bone ◽  
Prostate Specific Membrane Antigen ◽  
Ct Guided ◽  
Castration Resistant ◽  
Psma Pet ◽  
Pet Ct ◽  
Oligometastatic Prostate Cancer ◽  
Specific Membrane

213 Background: Metastases-directed therapy by metastasectomy or radiotherapy (RT) might delay disease progression and postpone systemic treatment in patients with oligometastatic prostate cancer. Here, we evaluated retrospectively the efficacy and toxicity of 68Ga prostate-specific membrane antigen (PSMA) PET-CT guided radiotherapy (RT) in the treatment of oligometastatic prostate cancer. Methods: A total of 23 prostate cancer patients with biochemical relapse, of which 13 castration-sensitive and 10 castration-resistant, were treated with intensity-modulated and image-guided RT (IMRT-IGRT) on ≤ 3 metastases detected by 68Ga PSMA PET-CT. Androgen deprivation therapy was continued in castration-resistant patients. Local control (LC), progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method. Results: A total of 38 metastases were treated. Involved sites were pelvic bone (n = 16), pelvic lymph nodes (n = 11), para-aortic lymph nodes (n = 6), ribs (n = 3) and vertebral body (n = 2). The median PSA prior to RT was 1.06 ng/ml (range 0.10 – 29.0 ng/ml). A median dose of 43.5 Gy (range, 30-64 Gy) was delivered by IMRT-IGRT in 12-27 fractions. At a median follow-up of 7 months (range, 2-17 months), 19 patients (83%) are in remission. Four patients (17%) developed distant recurrence. The actuarial 1-year LC, PFS and OS rates were 100%, 51% (95% CI 8-83%) and 100%. Castration-sensitive patients displayed a statistically significantly superior PFS on univariate analysis as compared to castration-resistant patients (1-year PFS 67% vs 0%, p < 0.01). One patient experienced grade 2 acute gastro-intestinal toxicity. No grade 3 or more toxic events were observed. Conclusions: By providing optimal LC, low toxicity and a promising PFS in castration-sensitive patients, the current retrospective study illustrated that 68Ga PSMA PET-CT guided RT may be an attractive treatment option in patients with oligometastatic prostate cancer. Validation by randomized trials is eagerly awaited.

scholarly journals 18F-PSMA-1007 PET in Biochemical Recurrent Prostate Cancer: An Updated Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Matteo Ferrari ◽  
Giorgio Treglia
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Meta Analysis ◽  
Emission Tomography ◽  
Prostate Specific Membrane Antigen ◽  
Targeted Agents ◽  
Recurrent Prostate Cancer ◽  
Positron Emission ◽  
Pet Ct ◽  
Specific Membrane

Background. Prostate-specific membrane antigen- (PSMA-) targeted agents labeled with fluorine-18 (18F) have recently become available to evaluate patients with biochemical recurrent prostate cancer (BRPCa) by using positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI). We performed a systematic review and meta-analysis about the detection rate (DR) of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa patients. Methods. A comprehensive computer literature search of PubMed/MEDLINE, EMBASE, and Cochrane Library databases for studies published through 17 May 2021 was carried out using the following search algorithm: “PSMA” AND “1007”. Only studies providing data on the DR of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa were included. A random-effects model was used to calculate the pooled DR on a per scan basis. Results. Fifteen articles (853 patients) were selected and included in the systematic review, and ten were included in the quantitative analysis. Most of the studies reported a good DR of 18F-PSMA-1007 PET/CT or PET/MRI in BRPCa including also patients with low prostate-specific membrane antigen (PSA) values. The DR of 18F-PSMA-1007 PET/CT or PET/MRI was dependent on PSA serum values. The pooled DR was 81.3% (95% confidence interval: 74.6–88%) with statistical heterogeneity. A significant reporting bias (publication bias) was not detected. Conclusions. 18F-PSMA-1007 PET/CT or PET/MRI showed a good DR in BRPCa patients in line with other PSMA-targeted agents. The DR of 18F-PSMA-1007 PET/CT or PET/MRI is influenced by serum PSA values. These findings should be confirmed by prospective multicentric trials.

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