PSMA-targeted imaging with 18F-DCFPyL-PET/CT in patients (pts) withbiochemically recurrent prostate cancer (PCa): A phase 3 study (CONDOR)—A subanalysis of correct localization rate (CLR) and positive predictive value (PPV) by standard of truth.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5023-5023
Author(s):  
Frederic Pouliot ◽  
Michael A. Gorin ◽  
Steven P. Rowe ◽  
Lawrence Saperstein ◽  
David Josephson ◽  
...  
Keyword(s):  
Lower Bound ◽  
Primary Endpoint ◽  
Local Therapy ◽  
Standard Of Care ◽  
Phase 3 ◽  
Correlative Imaging ◽  
Imaging Results ◽  
Pet Ct ◽  
Definitive Therapy ◽  
Psa Response

5023 Background: PSMA-targeted PET/CT is superior to conventional imaging modalities to localize biochemically recurrent (BCR) PCa after local therapy, particularly in pts with low PSA ( < 2 ng/mL). However, few studies have reported PSMA-targeted PET/CT accuracy compared to a pre-specified rigorous standard of truth (SOT) including histopathology, correlative imaging or treatment response in this population. Here, we report the CLR and PPV of PSMA-targeted 18F-DCFPyLPET/ CT, for each of the pre-defined SOT criteria for the CONDOR prospective phase 3 study. Methods: The study enrolled men with rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy, F-18 fluciclovine). A single 9 mCi (333 MBq) ± 20% dose of 18F-DCFPyL was injected, followed by PET/CT 1-2 hours later. Pts with positive 18F-DCFPyL-PET/CT scans based on local interpretation were scheduled for follow up within 60 days to verify suspected lesion(s) using a composite SOT. The primary endpoint was CLR defined as PPV with the requirement of anatomic lesion co-localization between 18F-DCFPyL-PET/CT and the SOT. The SOT consisted of, in descending priority: 1) histopathology, 2) subsequent correlative imaging findings determined by twocentral readers, or 3) post-radiation PSA response. The trial was successful if the lower bound of the 95% confidence interval for CLR exceeded 20% for at least two of three independent, blinded central 18F-DCFPyL-PET/CT reviewers. Results: 208 men (median PSA 0.8 ng/mL) underwent 18F-DCFPyL-PET/CT and the study achieved its primary endpoint: CLR was between 84.8% to 87.0% (lower bound of 95% CI: 77.8%-80.4%) among the three 18F-DCFPyL-PET/CT readers, against the composite SOT. The performance of 18F-DCFPyL-PET/CT by CLR (≥1 lesion co-localized) and PPV (≥1 lesion confirmed) was maintained through all 3 SOT categories. Histopathology (N = 31): 78.6-82.8% and 92.9-93.3% for CLR and PPV, respectively; correlative imaging (N = 100): 86.1-88.6% and 87.0-89.5% for CLR and PPV, respectively; and PSA response (N = 1): 100% for both CLR and PPV. Further analyses of the correlative imaging results showed CLR remained high across the different modalities used a) 18F-fluciclovine-PET/CT (N = 71): (86.8-90.9%); b) MRI (N = 23): (80.0-86.7%); and c) CT (n = 6): (80.0-100%). Conclusions: PSMA-targeted 18F-DCFPyL-PET/CT detected and localized metastatic lesions with high CLR and PPV regardless of which criterion defined CLR that was used, in men with BCR who had negative or equivocal baseline imaging. Clinicaltrials.gov: NCT03739684 Clinical trial information: NCT03739684.

PSMA-targeted imaging with 18F-DCFPyL-PET/CT in patients (pts) with biochemically recurrent prostate cancer (PCa): A phase III study (CONDOR)—A subanalysis of correct localization rate (CLR) and positive predictive value (PPV) by standard of truth.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 33-33
Author(s):  
Frederic Pouliot ◽  
Michael A. Gorin ◽  
Steven P. Rowe ◽  
Lawrence Saperstein ◽  
David Josephson ◽  
...  
Keyword(s):  
Lower Bound ◽  
Primary Endpoint ◽  
Local Therapy ◽  
Standard Of Care ◽  
Phase Iii ◽  
Correlative Imaging ◽  
Imaging Results ◽  
Pet Ct ◽  
Definitive Therapy ◽  
Psa Response

33 Background: PSMA-targeted PET/CT is superior to conventional imaging modalities to localize biochemically recurrent (BCR) PCa after local therapy, particularly in pts with low PSA (<2 ng/mL). However, few studies have reported PSMA-targeted PET/CT accuracy compared to a pre-specified rigorous standard of truth (SOT) including histopathology, correlative imaging or treatment response in this population. Here, we report the CLR and PPV of PSMA-targeted 18F-DCFPyL-PET/CT, for each of the pre-defined SOT criteria for the CONDOR prospective phase 3 study. Methods: The study enrolled men with rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy, F-18 fluciclovine). A single 9 mCi (333 MBq) ± 20% dose of 18F-DCFPyL was injected, followed by PET/CT 1-2 hours later. Pts with positive 18F-DCFPyL-PET/CT scans based on local interpretation were scheduled for follow up within 60 days to verify suspected lesion(s) using a composite SOT. The primary endpoint was CLR defined as PPV with the requirement of anatomic lesion co-localization between 18F-DCFPyL-PET/CT and the SOT. The SOT consisted of, in descending priority: 1) histopathology, 2) subsequent correlative imaging findings determined by two central readers, or 3) post-radiation PSA response. The trial was successful if the lower bound of the 95% confidence interval for CLR exceeded 20% for at least two of three independent, blinded central 18F-DCFPyL-PET/CT reviewers. Results: 208 men (median PSA 0.8 ng/mL) underwent 18F-DCFPyL-PET/CT and the study achieved its primary endpoint: CLR was between 84.8% to 87.0% (lower bound of 95% CI: 77.8%-80.4%) among the three 18F-DCFPyL-PET/CT readers, against the composite SOT. The performance of 18F-DCFPyL-PET/CT by CLR (≥1 lesion co-localized) and PPV (≥1 lesion confirmed) was maintained through all 3 SOT categories. Histopathology (N=31): 78.6-82.8% and 92.9-93.3% for CLR and PPV, respectively; correlative imaging (N=100): 86.1-88.6% and 87.0-89.5% for CLR and PPV, respectively; and PSA response (N=1): 100% for both CLR and PPV. Further analyses of the correlative imaging results showed CLR remained high across the different modalities used a) 18F-fluciclovine-PET/CT (N=71): (86.8-90.9%); b) MRI (N=23): (80.0-86.7%); and c) CT (n=6): (80.0-100%). Conclusions: PSMA-targeted 18F-DCFPyL-PET/CT detected and localized metastatic lesions with high CLR and PPV regardless of which criterion defined CLR that was used, in men with BCR who had negative or equivocal baseline imaging. Clinical trial information: NCT03739684.

scholarly journals A phase 3 randomised study of enzalutamide plus leuprolide and enzalutamide monotherapy in high-risk non-metastatic hormone-sensitive prostate cancer with rising PSA after local therapy: EMBARK study design

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e046588
Author(s):  
Stephen J Freedland ◽  
Ugo De Giorgi ◽  
Martin Gleave ◽  
Brad Rosbrook ◽  
Qi Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Specific Antigen ◽  
Local Therapy ◽  
Standard Of Care ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Randomised Study ◽  
Definitive Therapy

IntroductionLimited data from controlled clinical trials are available for men who experience biochemical recurrence after definitive therapy for prostate cancer. In the absence of overt metastases, patients with non-metastatic castration-sensitive prostate cancer (nmCSPC) often receive androgen deprivation therapy (ADT). There is no standard-of-care consensus on optimal ADT timing, although most men are treated prior to metastases, especially those with high-risk features (Gleason score 8–10 or prostate-specific antigen doubling time (PSADT) <9–12 months). Given data that ADT plus novel hormonal agents improve survival in men with metastatic CSPC, there is a desire to evaluate these agents earlier in the disease course. The main objective of EMBARK is the comparative assessment of enzalutamide plus leuprolide (luteinising hormone-releasing hormone agonist (LHRHa)) or enzalutamide monotherapy versus monotherapy LHRHa to improve metastasis-free survival (MFS) in patients with high-risk nmCSPC PSA recurrence after definitive therapy.Methods and analysisEMBARK is a randomised, phase 3 study of high-risk patients with nmCSPC, a PSADT of ≤9 months and a screening PSA of ≥2 ng/mL above the nadir after radiotherapy (RT) or ≥1 ng/mL after radical prostatectomy (RP) with or without postoperative RT. Men (n=1050) are randomised 1:1:1 to enzalutamide 160 mg/day plus LHRHa or placebo plus LHRHa (double-blind arms) or enzalutamide monotherapy (open-label arm). Treatment is suspended at week 37 if PSA concentrations are <0.2 ng/mL and reinstated if levels rise to ≥2.0 ng/mL with RP or ≥5.0 ng/mL without RP. Patients with PSA ≥0.2 ng/mL at week 37 continue until treatment discontinuation criteria are met. The primary endpoint is MFS comparing enzalutamide plus LHRHa versus placebo plus LHRHa.Ethics and disseminationThe study is conducted under the guiding principles of the World Medical Association Declaration of Helsinki. The results will be disseminated at research conferences and in peer-reviewed journals.Trial registration numberNCT02319837.

Impact of PSMA-targeted imaging with 18F-DCFPyL-PET/CT on clinical management of patients (pts) with biochemically recurrent (BCR) prostate cancer (PCa): Results from a phase III, prospective, multicenter study (CONDOR).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5501-5501 ◽  
Author(s):  
Michael J. Morris ◽  
Peter R. Carroll ◽  
Lawrence Saperstein ◽  
Frederic Pouliot ◽  
David Josephson ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Pet Imaging ◽  
Systemic Therapy ◽  
Clinical Management ◽  
Local Therapy ◽  
Phase Iii ◽  
Psma Pet ◽  
Pet Ct ◽  
Definitive Therapy ◽  
Occult Disease

5501 Background: Current imaging modalities are inadequate for localizing and characterizing occult disease in men with BCR PCa, particularly in pts with low PSAs (<2 ng/mL). There is a need for improved diagnostic imaging to better inform treatment planning. 18F-DCFPyL (PyL) is a novel PET imaging agent that binds selectively with high affinity to PSMA, which is overexpressed in PCa cells. Methods: Men ≥18 years- with rising PSA after definitive therapy and negative or equivocal standard of care imaging (e.g., CT/MRI, bone scintigraphy) were enrolled. A single 9 mCi (333 MBq) ± 20% dose of PyL was injected, followed by PET/CT 1-2 hours later. Primary endpoint was correct localization rate (CLR), defined as percentage of pts with a 1:1 correspondence between at least one lesion identified by PyL-PET/CT and the composite standard of truth: pathology, correlative imaging, or PSA response. The trial was successful if the lower bound of the 95% confidence interval (LLCI) for CLR exceeded 20% for two of three independent, blinded central PyL-PET/CT reviewers. The secondary endpoint, impact of PyL-PET/CT on clinical management of pts was based on the treating physician’s documented clinical plans before and after PyL-PET/CT. Results: 208 men (median PSA 0.8 [0.2 - 98.4] ng/mL) underwent PyL PET/CT. The study achieved its primary endpoint: CLR of 84.8% to 87.0% among the three PyL-PET/CT readers; the LLCI for CLR by all three reviewers was >77%. Here we report the clinical impact. Based on local radiology assessment, PSMA-avid lesion(s) were identified in 69.3% (142/208) of pts. 63.9% (131/205) had a change in intended management after PyL-PET/CT, of which 78.6% (103/131) were attributable to positive PyL finding(s) and 21.4% (28/131) to negative PyL scans. Changes included: salvage local therapy to systemic therapy (n=58); observation before initiating therapy (n=49); noncurative systemic therapy to salvage local therapy (n=43); and planned treatment to observation (n=9). PyL was well tolerated with one drug-related SAE (hypersensitivity) and the most common AE being headache (n=4; 1.9%). Conclusions: PSMA-targeted PyL-PET/CT detected and localized occult disease in most men with BCR presenting with negative or equivocal conventional imaging. PyL-PET/CT led to changed management plans in the majority of pts, thus providing evidence that clinicians find PSMA PET imaging useful in men with recurrent or suspected metastatic PCa. Clinical trial information: NCT03739684 .

scholarly journals OP0277 AURORA PHASE 3 STUDY DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 172.2-173 ◽  
Author(s):  
C. Arriens ◽  
S. Polyakova ◽  
I. Adzerikho ◽  
S. Randhawa ◽  
N. Solomons
Keyword(s):  
Primary Endpoint ◽  
Research Funding ◽  
Standard Of Care ◽  
Phase Iii ◽  
Therapeutic Drug ◽  
Phase 3 ◽  
Double Blind ◽  
Renal Response ◽  
Subgroup Analyses ◽  
And Control

Background:Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. LN occurs more frequently and is more severe in Hispanic/Latino ethnicity SLE patients. The recently completed phase 3 AURORA study builds on the favorable efficacy seen in the Phase IIb AURA-LV study in patients with active LN.Objectives:Document efficacy and safety of VCS vs placebo over one year when used with 2 grams of MMF daily and a rapid steroid taper in patients with active LN.Methods:AURORA is a Phase III multicenter, randomized, double-blind, placebo-controlled 52-week study of active LN patients. Patients were randomized 1:1 to VCS (23.7 mg BID) or placebo in combination with mycophenolate (MMF, 1 g BID) and rapidly tapered oral steroids. The primary endpoint was renal response (RR) at 52 weeks, defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of > 20%, presence of sustained, low dose steroids and no administration of rescue medication. Ethnicity subgroup analyses of RR was also undertaken given the higher severity of disease in the Hispanic/Latino LN patients.Results:There were 357 patients enrolled, 88% female, median age of 31 and 33% of Hispanic/Latino ethnicity. Renal response by intention to treat analysis at 52 weeks was 40.8% for the voclosporin arm and 22.5% for the control arm (OR: 2.65; 95% CI: 1.64, 4.27; p< 0.001); therefore, AURORA met its primary endpoint. These findings were consistent with those observed in the previously completed pivotal AURA-LV study. Ethnicity subgroup analysis of RR at 52 weeks noted benefit of VCS in both Hispanic/Latino (VCS 38.6% and control 18.6%, p=0.0062, OR 3.45) and non-Hispanic/Latino patients (VCS 41.8% and control 24.6%, p=0.0045, OR 2.29). The benefits of VCS were also seen for all pre-specified hierarchical secondary endpoints: RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) favored VCS. VCS was well tolerated with no unexpected safety signals. The overall incidence of SAEs were similar in both groups (VCS 20.8% and control 21.3%); with infection most commonly reported (VCS 10.1% and control 11.2%). Overall mortality in the trial was low, with one death in the voclosporin arm and five in the control arm. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids, or glucose.Conclusion:The AURORA study met its primary endpoint and VCS was efficacious in Hispanic/Latino ethnicity patients, a difficult to treat group.Disclosure of Interests:Cristina Arriens Grant/research support from: - BMS: Investigator Initiated Trial Research Funding, GSK: Investigator Initiated Trial Research Funding, Exagen: Research Grant, Consultant of: AstraZeneca (Sci Ad Board Dec 2017), GSK (Sci Ad Board Oct 2018), BMS (Sci Ad Board April 2019), Svetlana Polyakova: None declared, Igor Adzerikho: None declared, Simrat Randhawa Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals, Inc., Neil Solomons Shareholder of: Aurinia Pharmaceuticals, Inc. stock, Employee of: Aurinia Pharmaceuticals.

MO019AURORA PHASE 3 TRIAL DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Dawn J Caster ◽  
Neil Solomons ◽  
Simrat Randhawa ◽  
Robert B Huizinga
Keyword(s):  
Primary Endpoint ◽  
Standard Therapy ◽  
Low Dose ◽  
Statistical Significance ◽  
Standard Of Care ◽  
Therapeutic Drug ◽  
Control Group ◽  
Phase 3 ◽  
Double Blind ◽  
Renal Response

Abstract Background and Aims Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. The Aurinia Renal Response in Active Lupus with Voclosporin (AURORA) study, involving 357 patients with active LN, was a Phase 3 global, double-blind, placebo-controlled RCT designed to evaluate the efficacy and safety of VCS (23.7mg BID) vs placebo in combination with mycophenolate (MMF, 2 g/day) and rapidly tapered low dose oral steroids. Method The primary endpoint was renal response (RR) at 52 weeks. RR was defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of &gt; 20%, presence of sustained, low dose steroids and no administration of rescue medication. Results AURORA met its primary endpoint, achieving statistically superior RR rates of 40.8% for voclosporin vs. 22.5% for the control (OR 2.65, 95% CI; p &lt; 0.001). The benefits of VCS were also seen for all predetermined secondary endpoints, achieving statistical significance in favor of VCS for RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Prespecified confirmed eGFR decreases &gt;30% were similar in both groups, with 10.1% reported in the VCS group and 10.2% in the control arm (p= 0.971). No significant differences were seen at any timepoints in the study. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) also favored VCS. VCS was well tolerated with no unexpected safety signals. Similar SAEs were reported in the VCS group (20.8%) and in the control arm (21.3%). Infection was the most commonly reported SAE with 10.1% of VCS patients versus 11.2% of patients in the control arm. Overall mortality in the trial was low, with 6 deaths observed; 1 in the VCS arm and 5 in the control group. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids or glucose. Conclusion While maintaining a comparable safety profile, VCS plus standard therapy achieved a statistically superior RR over one year compared to placebo plus standard therapy in adults with active LN.

scholarly journals Daratumumab (DARA) Plus Lenalidomide Versus Lenalidomide Alone As Maintenance Treatment in Patients with Newly Diagnosed Multiple Myeloma (NDMM) after Frontline Autologous Stem Cell Transplant (ASCT): Use of Minimal Residual Disease (MRD) As a Novel Primary Endpoint in the Phase 3 Auriga Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1829-1829 ◽  
Author(s):  
Nina D. Shah ◽  
Yana Lutska ◽  
Huiling Pei ◽  
Ming Qi ◽  
Maria Krevvata ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Primary Endpoint ◽  
Research Funding ◽  
Maintenance Treatment ◽  
Standard Of Care ◽  
Consolidation Therapy ◽  
Employment Equity ◽  
Phase 3 ◽  
Advisory Committees ◽  
Equity Ownership

Background: DARA, a human anti-CD38 IgGκ monoclonal antibody, is approved in many countries as monotherapy in relapsed/refractory MM (RRMM), in combination with standard-of-care (SoC) regimens in RRMM and upfront in transplant ineligible NDMM. DARA is also under investigation as part of induction, consolidation, and maintenance treatment in patients with NDMM who are transplant eligible. However, no studies have specifically compared DARA maintenance to current SoC maintenance regimens. Although deep response as measured by MRD negativity has been associated with positive long-term clinical outcomes, and previous studies have demonstrated that DARA increases MRD negativity rates when combined with SoC therapy, MRD as a primary end point has not been examined in the context of frontline DARA treatment in NDMM. The ongoing phase 3 AURIGA (MMY3021) study will evaluate whether the addition of DARA to lenalidomide maintenance therapy increases the conversion rate to MRD negativity after 1 year of maintenance treatment, compared to lenalidomide alone, in patients with NDMM who are MRD positive after ASCT. Study Design and Methods: This ongoing multicenter, open-label, randomized phase 3 study will enroll approximately 214 patients from up to 60 sites in the United States. Patients 18-79 years of age are eligible if they have NDMM, have not been previously treated with an anti-CD38 antibody, have completed 4-8 total cycles of induction therapy (and/or consolidation therapy), have undergone ASCT, have achieved a very good partial response or better by International Myeloma Working Group (IMWG) criteria after ASCT and/or consolidation therapy, are MRD-positive by next-generation flow (NGF) or next-generation sequencing (NGS), at 60-100 days post-ASCT (or ≤60 days post consolidation therapy). Patients will be stratified by cytogenetic risk status (high risk vs standard risk/unknown status) and randomized 1:1 to DARA plus lenalidomide versus lenalidomide alone. Patients in both arms will receive 10 mg lenalidomide orally continuously during each 28-day cycle. After Cycle 3, if lenalidomide is well tolerated, the dose may be increased to 15 mg at the discretion of the investigator. Patients in the DARA plus lenalidomide arm will receive DARA SC (1,800 mg DARA co-formulated with recombinant human hyaluronidase PH20 [rHuPH20; 2,000 U/mL; ENHANZE® drug delivery technology, Halozyme, Inc.]) QW in Cycles 1-2, Q2W in Cycles 3-6, and Q4W thereafter. Treatment will continue until disease progression, unacceptable toxicity, withdrawal, or for a maximum of 36 cycles. The primary endpoint is the MRD-negativity conversion rate (assessed at a 10-5 sensitivity threshold) at 12 months of treatment, assessed via NGS. MRD will also be assessed at 6, 18, 24, and 36 months. Importantly, use of the novel primary endpoint of MRD-negativity will allow for earlier assessment of outcomes and evaluation of deeper response than traditional endpoints such as progression-free survival (PFS) and overall survival (OS). Secondary endpoints include overall MRD-negativity rate at any time, duration of MRD negativity, rate of complete response or better (≥CR), duration of ≥CR, PFS, OS, health-related quality of life, and safety. The ClinicalTrials.gov identifier is NCT03901963. Disclosures Shah: Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Indapta Therapeutics: Equity Ownership; Celgene, Janssen, Bluebird Bio, Sutro Biopharma: Research Funding; Poseida: Research Funding; Genentech, Seattle Genetics, Oncopeptides, Karoypharm, Surface Oncology, Precision biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi: Membership on an entity's Board of Directors or advisory committees; University of California, San Francisco: Employment; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Teneobio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Lutska:Janssen: Employment. Pei:Janssen: Employment, Equity Ownership. Qi:Janssen: Employment. Krevvata:Janssen: Employment. Kane:Janssen: Employment. Ukropec:Janssen: Employment, Equity Ownership. Lin:Janssen: Employment, Equity Ownership. Hampras:Janssen: Employment. OffLabel Disclosure: This presentation/paper includes information/discussion of a subcutaneous formulation of daratumumab, which is currently under investigation in several clinical trials, but has not yet been approved. The intravenous formulation of daratumumab is approved as monotherapy and in combination with standard-of-care regimens for the treatment of MM.

Prospective head-to-head comparison of 18F-fluciclovine and 68Ga-PSMA-11 PET/CT for localization of prostate cancer biochemical recurrence after primary prostatectomy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 15-15 ◽  
Author(s):  
Jeremie Calais ◽  
Francesco Ceci ◽  
Kathleen Nguyen ◽  
Jeannine Gartmann ◽  
Matthias Eiber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Detection Rate ◽  
Specific Antigen ◽  
Standard Of Care ◽  
Primary Study ◽  
Time Interval ◽  
Detection Rates ◽  
Pet Ct ◽  
Definitive Therapy

15 Background: 18F-Fluciclovine PET/CT (FACBC) is standard-of-care in US for localization of prostate cancer (PCa) biochemical recurrence (BCR) after definitive therapy. 68Ga-PSMA-11 PET/CT (PSMA) detects PCa BCR even at low prostate-specific antigen (PSA) levels (<2.0 ng/mL). We conducted a single-center prospective head-to-head comparison of these 2 PET/CT imaging tracers for localizing PCa BCR after radical prostatectomy (RP) in patients with PSA < 2.0 ng/ml. Methods: Patients with PCa BCR after RP and PSA levels ranging from ≥0.2 to ≤2.0 ng/mL without any prior salvage therapy were eligible. All patients underwent FACBC and PSMA scans within ≤15 days. Images analysis was performed a) by on-site clinical reading and b) by 3 blinded international expert readers for each modality. Detection rates on per-patient and per-region based analysis served as primary study endpoints. Based on literature data we hypothesized a detection rate difference of 22% in favor of PSMA. A power analysis determined a sample size of 50 patients. Results: The 50 patients were enrolled from March to September 2018. Median PSA level was 0.50 ng/ml. Median time interval between the 2 scans was 6 days. We present here the preliminary results from the non-blinded clinical reads. Detection rate on a per-patient basis was 69% for PSMA and 34% for FACBC. Concordant findings were observed in 30/49 patients (61%): 16/49 (32%) with both positive scans and 14/49 (29%) with both negative scans. Discordant findings were observed in 19/49 patients (39%): 18/49 (37%) had a positive PSMA but a negative FACBC scan while 1/49 (2%) had a positive FACBC with a negative PSMA (local recurrence). Detection rates were consistently lower for FACBC than for PSMA for all regions: Prostate bed (12% vs 20%), pelvic nodes (14% vs 37%), extra-pelvic nodes (2% vs 8%), skeleton (2% vs 8%) and visceral organs (2% vs 6%). Conclusions: This preliminary analysis from the non-blinded on-site clinical reads demonstrates prospectively that PSMA detection rates is more than double the FACBC detection rate in patients with PCa BCR after RP and with PSA ≤2.0 ng/ml. Clinical trial information: NCT03515577.

Randomized phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT].

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. TPS136-TPS136
Author(s):  
Jeremie Calais ◽  
Johannes Czernin ◽  
Wolfgang P Fendler ◽  
David Elashoff ◽  
Nicholas George Nickols
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Success Rate ◽  
Primary Endpoint ◽  
Salvage Radiotherapy ◽  
Phase Iii ◽  
Radiotherapy Planning ◽  
Phase 3 ◽  
Pet Ct ◽  
Biochemical Progression

TPS136 Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) biochemical recurrence (BCR) after radical prostatectomy (RP) is commonly initiated in patients with PSA < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. The purpose of this randomized phase 3 trial is to evaluate the success rate of SRT for PCa BCR after RP with and without planning based on 68Ga-PSMA-11 PET/CT (PSMA). Here we present the study protocol. Methods: This is an interventional phase 3 randomized prospective open label clinical trial with parallel assignment designed for superiority. Patients who are planned to undergo SRT for PCa BCR with PSA > 0.1 ng/ml are eligible. The choice of treating the prostate bed with/without pelvic lymph nodes, with/without androgen deprivation therapy, is left to the discretion of the treating radiation oncologist (RO). RO may or may not change the RT plan depending on the PSMA findings. Any other imaging is allowed for SRT planning if done per routine care. The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (PFS) after initiation of SRT. Biochemical progression is defined by PSA≥0.2 ng/mL and rising. Based on literature data we hypothesized that 1) the incorporation of PSMA to SRT planning will improve 5-year PFS by 20%, 2) the 5-year PFS will be 60% in standard Arm 1 and 80% in interventional Arm 2, and 3) 13% of subjects randomized to Arm 2 will have extra-pelvic metastasis detected by PSMA and will not be included in analysis of the primary endpoint. We will randomize 193 patients (1:1.13 ratio) to proceed with standard SRT (n = 90) or undergo PSMA scan (free of charge for patients) prior SRT planning (n = 103). Patients will be followed for 5 years after the date of initiation of SRT. Discussion: Main pitfalls in study design include 1) drop-out of patients randomized to the control arm and 2) potential FDA approval of PSMA PET imaging probes in the near future (no randomization to standard arm would be then acceptable). This is the first prospective randomized phase 3 trial designed to determine whether PET/CT can improve outcome of SRT in patients with BCR. Clinical trial information: NCT03582774.

Updated results of a phase I/II prospective dose escalation trial evaluating safety and efficacy of combination 177Lu PSMA 617 and idronoxil in men with mCRPC post androgen signalling inhibition and taxane chemotherapy (LuPIN trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5557-5557
Author(s):  
Louise Emmett ◽  
Sarennya Pathmanandavel ◽  
Megan Crumbaker ◽  
Christopher Rofe ◽  
Andrew On Wah Yam ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Nadh Oxidase ◽  
Standard Of Care ◽  
Pain Scores ◽  
Psma Pet ◽  
Pet Ct ◽  
Psa Response ◽  
Taxane Chemotherapy ◽  
End Stage

5557 Background: There is no established standard of care post cabazitaxel in men with mCRPC. Ongoing trials in 177LuPSMA-617 have demonstrated good efficacy and safety, but synergistic combinations may further improve treatment responses. Idronoxil (NOX66) inhibits external NADH oxidase type 2 with downstream pro-apoptotic actions including radio-sensitization. Herein we present updated results and an additional cohort of a prospective single arm phase I/II dose escalation/expansion trial of LuPSMA-617 and NOX66 in mCRPC. Methods: Men with progressive mCRPC post androgen signalling inhibition (ASI) and 2 lines of taxane chemotherapy were considered eligible. Key inclusion criteria included PSMA PET/CT intensity SUV max > 15 with no discordant disease on FDG PET/CT, Hb >10, Platelets >100 and GFR >40mls/min. Enrolled patients received up to 6 doses of 177 Lu-PSMA 617 (7.5Gbq) day 1 every 6 weeks in combination with NOX66 days 1-10 each cycle. Cohort 1 (n=8) received 400mg NOX66. Cohorts 2 and 3 subsequently received 800mg and 1200mg of NOX66, respectively, following safety reviews. Data regarding safety, efficacy, pain scores, and QOL were collected. Results: 32 men were enrolled in cohorts 1&2 (November 2017 – June 2019) and 24 in cohort 3 (August 2019-February 2020). To date there have been no dose-limiting toxicities. Data for cohort 3 are immature. For cohorts 1 & 2: 31/32 men received ≥2 cycles, with 12/32 (47%) completing 6 cycles. Any PSA response was seen in 84% (27/32), with a PSA response > 50% in 62.5% (20/32). Median PSA PFS is 6.1 months Of men with increased baseline pain scores ≥3 (24/32), 50% (12/24) had a clinically significant reduction in pain indicators. Adverse events are summarized below. Updated results for cohorts 1 and 2 and preliminary results of cohort 3 will be presented. Conclusions: Combination LuPSMA-617 + NOX 66 appears safe and efficacious in men with heavily pre-treated end stage mCRPC. Clinical trial information: ACTRN12618001073291 .

ATTAIN: Phase 3 study of etirinotecan pegol (EP) vs treatment of physician's choice (TPC) in patients (pts) with metastatic breast cancer (MBC) who have stable brain metastases (BM) previously treated with an anthracycline, a taxane, and capecitabine (ATC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1120-TPS1120
Author(s):  
Debu Tripathy ◽  
Sara M. Tolaney ◽  
Andrew David Seidman ◽  
Carey K. Anders ◽  
Nuhad K. Ibrahim ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Topoisomerase I ◽  
Single Agent ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Local Therapy ◽  
Cytotoxic Agents ◽  
Continuous Exposure ◽  
Phase 3 ◽  
Cns Lesions

TPS1120 Background: EP is a next generation topoisomerase I inhibitor-polymer conjugate that provides continuous exposure to SN-38, the active metabolite. A BM mouse model showed high penetration and retention of SN-38 in CNS lesions, resulting in decreased size of CNS lesions and improved survival (OS) at concentrations achieved at the recommended dose in pts (Adkins BMC Cancer 2015). A Phase 3 trial (BEACON) of EP vs TPC in 852 pts with advanced BC did not meet its primary endpoint of OS (HR 0.087; p = 0.08); a subset of 67 pts with stable BM showed improved OS (HR 0.51 [95% CI 0.30-0.86]; p < 0.01) (Perez Lancet Oncol 2015). The current Phase 3 trial (ATTAIN) was designed for this subpopulation of pts having high unmet medical need. Methods: Pts with MBC with locally treated stable BM will be randomized 1:1 to EP vs TPC in an open-label, randomized Phase 3 study. Eligibility includes ECOG PS 0 or 1; adequate organ function who received prior ATC (in neo/adjuvant or locally advanced/MBC setting); pts must have had ≥1 prior cytotoxic regimen for MBC (triple negative BC); ≥2 prior cytotoxic regimens and either 1 prior hormone therapy (HR+ BC) or 1 prior HER2 targeted therapy (HER2+ BC). Pts must have undergone definitive local therapy of BM (whole brain radiation [RT]; stereotactic RT or surgical resection as single-agent or combination); signs/symptoms of BM must be stable with steroids unchanged or decreasing for ≥7 days prior to randomization. Primary endpoint is OS. Key secondary endpoints: ORR and PFS by RECIST v1.1 and RANO-BM, clinical benefit rate (ORR+SD ≥ 6 months) and QoL. Pts randomized to TPC will receive 1 of 7 IV cytotoxic agents. Pts are stratified by region, PS and receptor status. 350 pts will be randomized to obtain number of events required at 90% power to detect a statistically significant improvement in OS (hypothesizing HR = 0.67); 1 interim analysis at 50% of deaths (130 events) will be performed. PK sampling and UGT1A1 testing will be performed in the EP arm; plasma ctDNA will be assessed for potential predictive markers of efficacy. Enrollment will begin early 2017. Clinical trial information: NCT02915744.

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