RESIST-PC phase 2 trial: 177Lu-PSMA-617 radionuclide therapy for metastatic castrate-resistant prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5028-5028 ◽  
Author(s):  
Jeremie Calais ◽  
Wolfgang P Fendler ◽  
Matthias Eiber ◽  
MIchael Lassmann ◽  
Magnus Dahlbom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Radionuclide Therapy ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Psma Pet ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

5028 Background: This is an investigator-initiated open-label prospective bi-centric single-arm phase 2 clinical trial (NCT03042312) of 177Lu-PSMA-617 radionuclide therapy in patients with progressive metastatic castrate-resistant prostate cancer (mCRPC). Methods: Patients with progressive mCRPC (biochemical, radiographic or clinical) after ≥1 novel androgen axis drug (NAAD), either chemotherapy (CTX) naïve or post-CTX, with sufficient bone marrow reserve and normal kidney function were eligible. All patients underwent a screening PSMA PET/CT to confirm target expression. Patients received up to 4 cycles of 177Lu-PSMA-617 every 8±1 weeks and were randomized into 2 treatment activities groups (6.0 or 7.4 GBq). Kidney dosimetry was performed for the first cycle. Efficacy was defined as serum PSA decline of ≥50% from baseline at 12 weeks and served as primary endpoint. Results: 64 patients (median PSA 75 ng/ml; range 0.5-2425) were included in the study. 20% were CTX naïve while 80% were post-CTX (1.9 CTX regimens on average, range 1-4). 45% completed 4 cycles of 177Lu-PSMA-617. Androgen deprivation therapy was given concomitantly in 83%, NAAD in 23% and immunotherapy in 6%. PSA decline of ≥50% was observed in 23% of patients at 12 weeks and in 38% of patients at any time (best PSA response). The median time to best PSA response was 22 weeks (range 6-49 weeks). 16% had a PSA decline of ≥90% and 59% had any PSA decline ( > 0%). Mild and transient (CTCAE grade 1-2) side effects included xerostomia (72%), nausea/vomiting (69%) and bowel movement disorders (45%). CTCAE grade 3 toxicity included nausea/vomiting (6%), anemia (8%), leukopenia (5%), kidney failure (3%), thrombocytopenia (3%), and neutropenia (3%). The mean kidney dose was 2.7 Gy for the first cycle (range 0.9-5.9) i.e. 0.4 Gy/GBq (range 0.15-0.9). There was no difference between the efficacy and toxicity for the 6.0 GBq (n = 23) and 7.4 GBq (n = 41) treatment arms. Conclusions: 177Lu-PSMA-617 radionuclide therapy is well tolerated in patients with progressive mCRPC. PSA declined by ≥50% in 38% of patients. The best PSA response rate occurred after 3 cycles. Updated data will be provided at the time of the conference. Clinical trial information: NCT03042312.

scholarly journals LBA-25 RESIST-PC PHASE 2 TRIAL: 177LU-PSMA-617 RADIONUCLIDE THERAPY FOR METASTATIC CASTRATE-RESISTANT PROSTATE CANCER

2019 ◽  
Vol 201 (Supplement 4) ◽  
Author(s):  
Jeremie Calais* ◽  
Wolfgang Fendler ◽  
Matthias Eiber ◽  
Michael Lassmann ◽  
Magnus Dahlbom ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radionuclide Therapy ◽  
Phase 2 ◽  
Phase 2 Trial ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

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.

Circulating androgen receptor (AR) gene amplification and resistance to 177Lu-PSMA-617 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results of a phase II clinical trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3020-3020 ◽  
Author(s):  
Ugo De Giorgi ◽  
Stefano Severi ◽  
Anna Sarnelli ◽  
Maddalena Sansovini ◽  
Manuela Monti ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Progressive Disease ◽  
Gene Gain ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Early Assessment ◽  
Psma Pet ◽  
Psa Response ◽  
Early Progressive Disease

3020 Background: Plasma AR gain is associated with poor prognosis in mCRPC pts treated with abiraterone/enzalutamide, however these pts could benefit from docetaxel (Conteduca et al, Eur Urol 2019). In a phase 2 clinical trial with 177Lu-PSMA-617 in mCRPC pts who progressed after standard survival-prolonging treatments, we aimed to determine if plasma AR gene status enable early assessment of 177Lu-PSMA-617 activity for mCRPC. Methods: Between April 2017 and November 2018, 43 mCRPC pts were treated with 177Lu-PSMA-617 in a phase 2 study. Pts younger than 75 years and not heavily pretreated received 5.5 GBq of 177Lu-PSMA-617, while other pts received 4.2 GBq per cycle, for a total of 4-6 cycles, q8 weeks. We determined AR copy number by droplet digital polymerase chain reaction (ddPCR) on pretreatment plasma samples. We evaluated associations between plasma AR amplification and PSA response (≥50% PSA decline from baseline) and imaging response/progression (as measured by bone scan, CT, and PSMA PET/CT). Logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (95% CI) in order to evaluate the independent relevance of AR status and pts without PSA response and those with early progressive disease defined as treatment interruption occurring within 4 months of the start of 177Lu-PSMA-617. Results: Forty of 43 pts (median age: 72 years, range 54-86) were fully evaluable for this analysis. A PSA response was reported in 15 (37.5%) of the 40 pts, 3 of 15 (20%) with AR gene gain, and 12 of 25 (48%) with no gain (P = 0.080). Early progressive disease was observed in 17 (42.5%) of the 40 pts, 12 of 15 (80%) with AR gene gain and 5 of 25 (20%) with no gain (P = 0.0002). The OR for pts without PSA response (decline < 50%) having AR gain was 3.69, 95% CI 0.83-16.36, p = 0.085. The OR for pts with early PD having AR gain was 16.00, 95% CI 3.23-79.27, p = 0.0007. The evaluation of germline alterations in DNA damage repair (DDR) genes is ongoing (i.e., BRCA2, BRCA1, ATM). Conclusions: Plasma AR status assessment using ddPCR identifies mCRPC resistant to 177Lu-PSMA-617. These data suggest potential better activity of 177Lu-PSMA-617 in earlier phases of prostate cancer. Prospective evaluation of treatment decision making based on plasma AR status is warranted. Clinical trial information: NCT03454750.

scholarly journals Openact: Phase 2, Open-Label Study of Sipuleucel-T in Metastatic Castrate-Resistant Prostate Cancer (MCRPC)

2012 ◽  
Vol 23 ◽  
pp. ix311
Author(s):  
J. Corman ◽  
N. Dawson ◽  
S. Hall ◽  
C. Nabhan ◽  
A. Ferrari ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase 2 ◽  
Open Label ◽  
Open Label Study ◽  
Label Study ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

scholarly journals USE OF 177Lu-PSMA FOR RADIONUCLIDE THERAPY IN PATIENTS WITH CASTRATE-RESISTANT PROSTATE CANCER

2021 ◽  
Vol 20 (3) ◽  
pp. 115-123
Author(s):  
A. A. Medvedeva ◽  
V. I. Chernov ◽  
E. A. Usynin ◽  
R. V. Zelchan ◽  
O. D. Bragina ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radionuclide Therapy ◽  
Malignant Tumors ◽  
Tumor Grade ◽  
Current Data ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psma Pet ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Purpose of the study: to present current data regarding challenges in treatment of castration-resistant prostate cancer (CRPC) and the relationship between CRPC and the expression of prostate-specific membrane antigen (psma).Material and Methods. The search for relevant sources was carried out in the Pubmed, elibrary, Medline databases. The review included 43 publications, most of which were published over the past 5 years.Results. Currently, prostate cancer (PC) is one of the most common cancers in men. Moreover, over time, most patients develop resistance to therapy, which significantly worsens the prognosis of the disease. Psma is one of the molecular markers of prostate cancer; a number of studies have demonstrated a direct correlation between the level of psma expression and the tumor grade, stage and aggressiveness. Numerous studies indicate that psma represents an excellent target for radionuclide therapy of prostate cancer. 68Ga or 18F-psma Pet/Ct is the most common method for diagnosing PC. It should be noted that modern trends in the development of nuclear medicine are closely related to theranostics; therefore, the creation of highly specific theranostic pairs for diagnosis and subsequent therapy of malignant tumors is of great significance. The data obtained indicate that 177lu demonstrates the most optimal radiation and physical characteristics for therapeutic radionuclides, while psma-617 is one of the most studied ligands for radionuclide therapy.Conclusion. Currently, there are several studies covering radionuclide therapy with various psmacompounds labeled with 177lu. Radionuclide therapy with 177lu-psma has been shown to be recommended for patients with metastatic CRPC, who have no benefits from alternative therapies or have contraindications to them.

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