VERU-111, an oral cytoskeleton disruptor, to treat men with metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5056-5056
Author(s):  
Mark Christopher Markowski ◽  
Ronald F. Tutrone ◽  
Mario A. Eisenberger ◽  
Christopher Michael Pieczonka ◽  
Robert H. Getzenberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Androgen Receptor ◽  
Study Entry ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Multidrug Resistance Proteins ◽  
Receptor Targeting ◽  
Phase 1B ◽  
Grade 3 ◽  
Moderate Nausea

5056 Background: VERU-111 is an oral cytoskeletal disruptor that disrupts microtubules supporting the cytoskeleton and has no affinity for multidrug resistance proteins. A phase 1b/2 clinical study has been conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC also resistant to androgen receptor targeting agents. Methods: In the phase 1b component of the study, a 3+3 design with escalating oral dosing of 4.5 mg to 81 mg (7 days on drug/14 days off per 21-day cycle) was utilized. The schedule was also expanded to continuous dosing/cycle. The phase 2 portion utilized 63 mg daily dosing to evaluate efficacy in approximately 40 taxane-naïve men with mCRPC that have failed at least one androgen receptor targeting agent. Results: In the phase 1b portion of the study, 30 taxane-naïve men with mCRPC and a median age of 76 (61-92) were enrolled. 8 had received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases at study entry. The MTD of VERU-111 is 72mg (3/11 men had grade 3 diarrhea) and the recommended phase 2 dose is 63mg. Grade 3 diarrhea was not observed at doses ≤ 63mg per day and the most common non-dose limiting AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. Efficacy was assessed by PSA and bone/CT scans. In men treated for ≥ 4 continuous 21-day cycles, 6/10 (60%) had PSA declines, 4(40%) men had ≥ 30% declines and 2(20%) ≥ 50% declines compared to their 21-day cycle baseline PSA. Median PFS is currently 12 months (6-23+ months) with 3 patients continuing on study, 2 of which have been on study for approximately 2 years. In patients receiving at least a single dose of ≥ 63 mg daily (n=19), objective tumor responses were seen in 3 men (16%). The median rPFS in these patients is currently 12.4 months. In the phase 2 portion of the study, 55% of the patients had bone only metastases, 11% had nodal only, 32% had mixed bone and nodal disease and 3% had visceral disease at study entry. 6/32 (19%) were previously treated with abiraterone alone, 12/32 (38%) with enzalutamide alone, and 14/32 (44%) had abiraterone in combination with enzalutamide, proxalutamide or apalutamide. The phase 2 portion of the study is ongoing and objective tumor responses have been observed including a CR and PRs and PSA decreases >50%. Patients have been on study as long as 9 months. Conclusions: This phase 1b/2 clinical trial, demonstrates that oral daily dosing of VERU-111 has a favorable safety profile and that chronic dosing is feasible. The recommended phase 2 dose of 63mg daily has significant durable antitumor activity. These data support a potential prominent role of VERU 111 for the treatment of men with mCRPC who previously failed an androgen receptor targeting agent and prior to the administration of intravenous chemotherapy. Clinical trial information: NCT03752099.

Clinical study of VERU-111, an oral cytoskeletal disruptor, in metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 131-131
Author(s):  
Mark Christopher Markowski ◽  
Mario A. Eisenberger ◽  
Ronald F. Tutrone ◽  
Christopher Michael Pieczonka ◽  
Robert H. Getzenberg ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Androgen Receptor ◽  
Clinical Study ◽  
Soft Tissue ◽  
Antitumor Activity ◽  
Phase 2 ◽  
Nodal Disease ◽  
Receptor Targeting ◽  
Phase 1B ◽  
Grade 3

131 Background: VERU-111 is an oral, cytoskeletal disruptor that crosslinks α & ß tubulin and inhibits microtubule polymerization with no affinity for multidrug resistance proteins. A Phase 1b/2 clinical study has been conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with progressive mCRPC resistant to androgen receptor targeting agent (ARTA). Methods: In the Phase 1b portion of the study, a 3+3 design with escalating oral dosing of 4.5 - 81 mg (7 days on drug/14 days off per 21 day cycle) was utilized. After no dose limiting toxicity was observed, the dose was increased in the next cohort. The schedule was also expanded in those completing the 7 days on/14 days off cycle to continuous dosing/cycle. The recommended Phase 2 study dose is 63 mg daily and the trial is fully enrolled with 40 taxane-naiive men with mCRPC that have failed at least one ARTA. Results: In the Phase 1 portion of the study, 30 taxane-naïve mCRPC men with a median age of 76 (61-92) were enrolled. 8 received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases. The MTD of VERU-111 is 72mg (3 /11 men had Grade 3 diarrhea). No Grade 3 diarrhea was observed at doses < 72 mg per day. At doses < 72mg/d, the most common AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. In the Phase 1b, antitumor activity was assessed by PSA and bone/CT scans in men that were treated for ≥ 4 continuous 21-day cycles. 6/10 (60%) had PSA declines: 4 (40%) men had ≥ 30% and 2(20%) ≥ 50% declines compared to their 21 day cycle baseline. Based on PCWG3/RECIST 1.1 criteria, objective tumor responses were seen in 2 men (soft tissue and bone). Median duration of response is 11 months (6-18+ months). In the Phase 2 portion of the study, 49% had bone only metastases, 54% have bone only metastases, 11% have nodal disease, 32% had mixed bone and nodal disease and 3% had visceral disease. This portion of the study is ongoing and results will be reported. 9/29 (31%) had previously abiraterone, 10/29 (34%)( enzalutmide, 7/29 (24%) both enzalutmide and abiraterone and 4/29 (14%) apalutamide. Conclusions: Based upon this Phase 1b/2 clinical trial, oral VERU-111 has a favorable safety profile allowing for chronic administration and significant and durable antitumor activity. The daily dose of 63mg is being tested in the fully enrolled Phase 2 portion. Oral administration, safe long-term treatment and evidence of antitumor activity highlight a potential prominent role of VERU 111 for the treatment of men with mCRPC who failed an androgen receptor targeting agent. Clinical trial information: NCT03752099.

Phase 1b/2 study of enzalutamide (ENZ) with LY3023414 (LY) or placebo (PL) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) after progression on abiraterone.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5009-5009 ◽  
Author(s):  
Christopher Sweeney ◽  
Ivor John Percent ◽  
Sunil Babu ◽  
Jennifer Cultrera ◽  
Bryan Allyn Mehlhaff ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Phase 1 ◽  
Single Agent ◽  
Progression Free Survival ◽  
Primary Objective ◽  
P Value ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Phase 1B

5009 Background: Preclinical and phase 1 results suggest PI3K/mTOR pathway inhibition may enhance androgen receptor inhibition. We report the results of a double-blind, placebo-controlled, randomized Phase 1b/2 study of ENZ±LY (a dual PI3K/mTOR inhibitor) in pts with mCRPC who progressed on abiraterone. Methods: Phase 1b pts received single-agent LY 200 mg twice daily (BID) for 1 wk prior to starting LY+ENZ. Phase 2 pts were randomized 1:1 to 160 mg daily ENZ with PL or 200 mg BID LY on a 28-d cycle. The primary objective was progression-free survival (PFS: serological, radiographic [rPFS], or death) by PCWG2 criteria. Secondary objectives were rPFS, safety, decline in PSA, and PK. Exploratory biomarker analyses included outcomes by presence of androgen receptor variant 7 (AR-V7). 92 primary PFS events were needed for the study to have at least 80% power at one-sided alpha=0.20. Results: LY+ENZ was tolerable during Phase 1b with 1 dose limiting toxicity observed in 13 enrolled pts. Mean LY exposures remained in an efficacious range despite a 30% average decrease when combined with ENZ. In Phase 2, 129 pts were randomized to LY+ENZ (N=65) and PL+ENZ (N=64) (Table). Median PCWG2-PFS was 3.7 mos (LY+ENZ) vs 2.9 mos (PL+ENZ) (HR 0.66, 95% CI 0.43, 0.99; p-value 0.0208). Conclusions: Combination LY+ENZ had a clinically manageable safety profile. The primary end-point of PCWG2-PFS was met and is supported by a clinically meaningful delay in rPFS in AR-V7 negative pts. The biomarker data provide important insights to inform future development strategies. Clinical trial information: NCT02407054. [Table: see text]

scholarly journals Phase 2 Study of Blinatumomab in Japanese Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia (R/R ALL)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5167-5167
Author(s):  
Yukio Kobayashi ◽  
Zachary F. Zimmerman ◽  
Iekuni Oh ◽  
Yoshinobu Maeda ◽  
Hironobu Minami ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Research Funding ◽  
Global Studies ◽  
Phase 2 ◽  
Clinical Trial Research ◽  
Japanese Adults ◽  
Phase 2 Study ◽  
Phase 1B ◽  
Grade 3

Abstract Introduction: Blinatumomab is an anti-CD3/CD19 bispecific T-cell engager antibody construct that has antileukemic activity in adult patients with R/R ALL. The objectives of this open-label, multicenter, phase 2 study were to determine the efficacy and safety of the recommended dose level of blinatumomab (identified in the phase 1b part of the study) in Japanese adults with R/R B-precursor ALL. Methods: Eligible patients were ≥ 18 years old with R/R ALL (first remission duration ≤ 12 months, after first salvage, or within 12 months after allogeneic hematopoietic stem cell transplantation [alloHSCT]), > 5% blasts, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2, and no central nervous system pathology. The primary endpoint was complete remission/complete remission with partial hematological recovery (CR/CRh) within 2 cycles of treatment with blinatumomab; additional endpoints included relapse-free survival (RFS), overall survival (OS), minimal residual disease (MRD) response, the incidence and severity of adverse events (AEs), and the incidence of anti-blinatumomab antibody formation. Consistent with global studies, the selected phase 2 dose identified in the phase 1b part was 9-28 μg/day, and patients received induction blinatumomab for 4 weeks by continuous intravenous infusion (cycle 1/week 1: 9 μg/day; cycle 1/weeks 2-4: 28 μg/day; subsequent cycles: 28 μg/day) followed by 2 weeks of no blinatumomab (each cycle). Patients who achieved a bone marrow response (≤ 5% blasts) within 2 induction cycles received additional consolidation cycles of blinatumomab, up to a maximum of 5 total induction/consolidation cycles. Results: Twenty-one patients enrolled between April 2016 and June 2017 received blinatumomab 9-28 μg/day (median 2 [range, 1-3] cycles). Twelve of the 21 patients (57%) were women; the median (range) age was 43 (18-55) years; 9 patients (43%) had prior HSCT; 7 patients (33%) had 1 prior salvage therapy, 4 patients had 2 prior salvage therapies, and 3 patients had more than 2 prior salvage therapies; and the median (range) percentage of bone marrow blasts was 69% (7%-96%). Responses during the first 2 cycles of treatment with blinatumomab are shown in the table. CR/CRh during the first 2 cycles was observed in 8 patients (38%); 3 of 7 patients who achieved CR/CRh and had evaluable MRD had a complete MRD response. Among the 8 patients who achieved CR/CRh during the first 2 cycles, the median RFS was 5 months (95% CI: 3.5-6.4 months), with a median (range) follow-up time of 2.2 (0-2.8) months; the Kaplan-Meier estimate of RFS was 100%, 50%, and 0% at 3, 6, and 12 months, respectively. At the data cutoff date (August 24, 2017), 2 patients had died, and OS was not estimable. Fourteen patients (67%) received an HSCT during long-term follow-up, 10 (48%) of whom did not receive other anti-cancer therapy before HSCT; 5 of the 10 patients achieved CR/CRh during the blinatumomab treatment period. All 21 patients reported AEs: 21 (100%) with grade ≥ 3 AEs, 14 (67%) with grade ≥ 4 AEs, 7 (33%) with serious AEs, 4 (19%) with AEs that led to interruption/discontinuation of blinatumomab, and 1 (5%) with a fatal AE (tumor lysis syndrome in the setting of disease progression). The most common AEs (≥ 10 patients) were pyrexia in 15 patients (71%) and febrile neutropenia (all grade ≥ 3) in 10 patients (48%). Eight patients (38%) had cytokine release syndrome (1 serious, grade ≥ 3), and 9 patients (43%) had neurologic events (1 grade ≥ 3). Other serious AEs were decreased neutrophil count (2 patients) and bacteremia, colitis, decreased appetite, and device-related infection (1 patient each). No anti-blinatumomab antibodies were detected in any patient. Conclusions: This study demonstrated the efficacy and safety of the recommended dose level of blinatumomab in a high-risk adult R/R ALL population. Response rates in Japanese patients were consistent with those in global studies, and no new safety signals were identified. Disclosures Kobayashi: Ohtuka: Research Funding; Pfizer: Research Funding; Astellas: Research Funding. Zimmerman:Amgen Inc.: Employment, Equity Ownership. Minami:Kyowa-Kirin: Honoraria, Research Funding; MSD: Honoraria, Other: Clinical Trial, Research Funding; Ono Yakuhin: Honoraria, Other: Clinical Trial, Research Funding; Behringer: Honoraria, Research Funding; AstraZeneca: Other: Clinical Trial; Pfizer: Honoraria, Research Funding; Teijin Pharma: Research Funding; Astellas: Research Funding; Ohtsuka: Honoraria; Taiho: Honoraria, Other: Clinical Trial, Research Funding; Bristol-Myers Squibb: Honoraria, Other: Clinical Trial, Research Funding; Kowa: Honoraria; Eizai: Honoraria, Research Funding; Taisho-Toyama: Research Funding; DaiNihonSumitomo: Honoraria, Research Funding; DaiichiSankyo: Honoraria, Other: Clinical Trial, Research Funding; Chugai: Honoraria, Other: Clinical Trial, Research Funding; Janssen: Honoraria; Celgene: Clinical Trial, Honoraria; Takeda: Honoraria, Research Funding; Shire Japan: Honoraria; Eizai: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Bayer: Honoraria, Other: Clinical Trial, Research Funding; Merck Serono: Honoraria; Nihon Shinyaku: Research Funding; Lilly: Honoraria, Research Funding; Yakult: Research Funding; Nippon Chemiphar: Honoraria, Research Funding; Mochida: Honoraria; Asahi-Kasei Pharma: Research Funding. Iida:Chugai Pharmaceutical Co., Ltd.: Research Funding. Chen:Amgen, Inc: Employment, Equity Ownership. Kiyoi:Kyowa Hakko Kirin Co., Ltd.: Research Funding; Astellas Pharma Inc.: Research Funding; Celgene Corporation: Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; FUJIFILM Corporation: Research Funding; Phizer Japan Inc.: Research Funding; Chugai Pharmaceutical Co., Ltd.: Research Funding; Nippon Shinyaku Co., Ltd.: Research Funding; Eisai Co., Ltd.: Research Funding; Bristol-Myers Squibb: Honoraria; Zenyaku Kogyo Co., Ltd.: Research Funding; Takeda Pharmaceutical Co., Ltd.: Research Funding; Novartis Pharma K.K.: Research Funding; Sumitomo Dainippon Pharma Co., Ltd.: Research Funding; Sanofi K.K.: Research Funding.

Multicenter phase Ib/II study of second-line trastuzumab, ramucirumab, and paclitaxel in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (HER-RAM study).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4063-4063
Author(s):  
Sun Young Rha ◽  
Chang Gon Kim ◽  
Minkyu Jung ◽  
Hyo Song Kim ◽  
Choong-kun Lee ◽  
...  
Keyword(s):  
Dose Level ◽  
Gastroesophageal Junction ◽  
Second Line ◽  
Phase 2 ◽  
Gi Bleeding ◽  
Her2 Positive ◽  
Phase 1B ◽  
Her 2 ◽  
Level 1 ◽  
Grade 3

4063 Background: We evaluated the safety and efficacy of adding trastuzumab to ramucirumab and paclitaxel (TRP) as a second line treatment in human epidermal growth factor receptor 2 (HER-2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer progressed from trastuzumab containing chemotherapy. Methods: Patients with HER-2-positive advanced G/GEJ cancer who progressed after first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Trastuzumab (Herzuma[CT-P6], Celltrion Inc.) 4mg/kg on day 1 followed by 2mg/kg on days 8, 15, and 22, ramucirumab 8mg/kg on days 1 and 15, and paclitaxel (dose level 1: 80mg/m2, dose level -1: 70 mg/m2) on days 1, 8, and 15 of a 28-day cycle was tested. After safety analysis of lead-in safety cohort (phase 1b), phase 2 part was conducted to evaluate the primary endpoint of progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: At the phase 1b part, as there was no dose limiting toxicity in 3 patients at the dose level 1, dose level 1 with full dose combination was determined as recommended phase 2 dose. At the time of data lock on Jan. 31, 2021, 45 patients among enrolled 50 patients were evaluable for response and safety including 3 patients from phase 1b part. Median age was 59 years old (range 30-82) and most patients were male (37/45). At baseline, 33 patients had tumors with HER-2 3+ by immunohistochemistry (IHC) and 12 had those with HER-2 2+ by IHC with ERBB2 amplification by in situ hybridization. With median follow-up duration of 11.6 months, median PFS and OS were 7.2 months (95% confidence interval [CI]: 6.0-8.5 months) and 13.6 months (95% CI: 10.3-16.9 months), respectively. ORR was 55.6% (25/45, complete response = 1, partial response = 24) and DCR was 95.6% (43/45), respectively. Most common hematologic adverse event (AE) was neutropenia (all grade: 64.4%, grade 3/4: 51.1%) with 1 case of febrile neutropenia (2.2%). Most common non-hematologic AE was peripheral sensory neuropathy (all grade: 33.3%, grade 3: 2.2%). Gastrointestinal (GI) bleeding occurred in 4 patients (grade 3 upper GI bleeding: 6.7%, grade 1 lower GI bleeding: 2.2%), whereas GI perforation was not observed. Hypertension occurred in 3 patients (all grade: 6.7%, grade 3: 4.4%). No new or unexpected AEs resulting in treatment cessation were observed with this combination regimen. Conclusions: The continuous use of trastuzumab beyond progression in combination with ramucirumab and paclitaxel showed promising activity and manageable safety profile in HER2 positive G/GEJ cancer patients who progressed after trastuzumab containing chemotherapy. Updated outcomes for ongoing patients will be presented.

scholarly journals Venetoclax plus R- or G-CHOP in non-Hodgkin lymphoma: results from the CAVALLI phase 1b trial

Blood ◽  
2019 ◽  
Vol 133 (18) ◽  
pp. 1964-1976 ◽  
Author(s):  
Andrew D. Zelenetz ◽  
Gilles Salles ◽  
Kylie D. Mason ◽  
Carla Casulo ◽  
Steven Le Gouill ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Phase 2 ◽  
Non Hodgkin Lymphoma ◽  
Phase 1B ◽  
Grade 3

Abstract Novel strategies, such as chemosensitization with targeted agents, that build on the success of standard immunochemotherapy show promise for the treatment of non-Hodgkin lymphoma (NHL). Here, we report a phase 1b study investigating dose escalation of the BCL2 inhibitor, venetoclax, in combination with rituximab or obinutuzumab and cyclophosphamide, doxorubicin, vincristine, and prednisone (R-/G-CHOP) chemotherapy in B-cell NHL. Objectives included safety assessment and determination of a recommended phase 2 dose (RP2D). Fifty-six patients were enrolled, most with follicular lymphoma (43%) or diffuse large B-cell lymphoma (DLBCL; 32%). Dose-limiting toxicities were reported in 3/14 patients at the first venetoclax dose (200 mg/d), after which dosing was changed from daily to 10 days per cycle and escalated to 800 mg. A further reduction to 5 days per cycle occurred at the 800-mg dose level in the G-CHOP arm. Cytopenias were predominant among grade 3/4 events and reported at a higher rate than expected, particularly in the G-CHOP arm; however, safety was manageable. Overall response rates were 87.5% (R-CHOP and G-CHOP combinations); complete response (CR) rates were 79.2% and 78.1%, respectively. Most double-expressor (BCL2+ and MYC+) DLBCL patients (87.5%; n = 7/8) achieved CR. Although the maximum tolerated dose was not reached, the RP2D for venetoclax with R-CHOP was established at 800 mg days 4 to 10 of cycle 1 and days 1 to 10 of cycles 2 to 8; higher doses were not explored, and this dosing schedule demonstrated an acceptable safety profile. This regimen is subsequently being evaluated in first-line DLBCL in the phase 2 portion of the study. This trial was registered at www.clinicaltrials.gov as #NCT02055820.

scholarly journals A phase 2 clinical trial of everolimus plus bicalutamide for castration-resistant prostate cancer

Cancer ◽  
2016 ◽  
Vol 122 (12) ◽  
pp. 1897-1904 ◽  
Author(s):  
Helen Chow ◽  
Paramita M. Ghosh ◽  
Ralph deVere White ◽  
Christopher P. Evans ◽  
Marc A. Dall'Era ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Phase 2 Clinical Trial

A phase II randomized clinical trial of samarium-153 EDTMP (Sm-153) with or without PSA-TRICOM vaccine in metastatic castration-resistant prostate cancer (mCRPC) after docetaxel.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Christopher Ryan Heery ◽  
Ravi Amrit Madan ◽  
Marijo Bilusic ◽  
Joseph W. Kim ◽  
Nishith K. Singh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Exact Test ◽  
Phase 2 Trial ◽  
Radium 223 ◽  
Immune Mediated ◽  
Early Closure

102 Background: A prior randomized, placebo-controlled, multi-center phase 2 trial of PSA-TRICOM demonstrated survival benefit. Sm-153 is a radiopharmaceutical that targets osteoblastic lesions. Preclinical data indicated that Sm-153 could alter tumor phenotype, causing upregulation of Fas, MHC Class I, and tumor-associated antigens, making tumor cells more amenable to immune-mediated killing. This trial was intended to examine the safety and efficacy of the Sm-153 with PSA-TRICOM vs. Sm-153 alone. Methods: This phase 2 multi-center trial was designed to randomize 68 pts to Sm-153 with or without PSA-TRICOM. Eligibility included mCRPC, bone metastases, no visceral disease, prior docetaxel, ECOG ≤2, and normal organ function. Sm-153 was given at 1mCi/kg IV on day 8 and then every 12 weeks. PSA-TRICOM was given on days 1, 15, 29, then every 4 weeks. The 1° endpoint was comparison of progression-free survival at 4 months (mo) utilizing PCCWG, but not PSA criteria. A Fisher’s exact test, assuming a one-tailed alpha = 0.10, was used to compare these fractions. 2° endpoints were OS, ORR, PSA changes, immunologic, and toxicity. Results: 44 pts were enrolled, 5 were not evaluable for the 1° endpoint due to withdrawal prior to 4 mos (4 on Arm A, 1 on Arm B). PFS and PSA findings are provided below. Hematologic toxicities were most common, and were well matched. Conclusions: This final analysis suggests the combination of PSA-TRICOM and Sm-153 has a similar toxicity profile to Sm-153 alone. Despite early closure of this trial due to poor accrual, which may be related to recent approval of multiple agents for mCRPC, this analysis appears to demonstrate improvement in PFS with the combination. This may indicate synergy between PSA-TRICOM and bone-seeking radiopharmaceuticals. Based on the data presented here, we are exploring the potential to combine PSA-TRICOM with alpharadin (radium-223), a next generation bone-seeking radiopharmaceutical. Clinical trial information: NCT00450619. [Table: see text]

Update on KEYNOTE-199, cohorts 1-3: Pembrolizumab (pembro) for docetaxel-pretreated metastatic castration-resistant prostate cancer (mCRPC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 104-104 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Josep M. Piulats ◽  
Marine Gross-Goupil ◽  
Jeffrey C. Goh ◽  
Ulka N. Vaishampayan ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Response Rate ◽  
Phase 2 ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Phase 2 Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Clinical Trial Information

104 Background: The KEYNOTE-199 multicohort phase 2 study (NCT02787005) showed that pembro monotherapy has antitumor activity and acceptable safety in patients (pts) with mCRPC previously treated with a next-generation hormonal agent (NHA) and docetaxel in cohort 1 (C1) (RECIST-measurable, PD-L1+ disease), C2 (RECIST-measurable, PD-L1− disease), and C3 (bone-predominant disease, irrespective of PD-L1). Updated results with additional follow-up for C1-3 are presented. Methods: Pts previously received ≥1 NHAs and 1 or 2 chemotherapies, including docetaxel. Pts received pembro 200 mg Q3W for 35 cycles or until progression or intolerable toxicity. Primary end point was ORR. Key secondary end points were DCR, DOR, PSA (≥50%) response rate, rPFS, OS, and safety. Results: Of 258 pts enrolled (C1=133; C2=67; C3=58), 6 completed (C1=4; C3=2) and 252 discontinued (C1=129; C2=67; C3=56) therapy, primarily due to progression (C1=106; C2=61; C3=45). Median follow-up was 9.6 mo (C1, 9.5; C2, 7.9; C3, 14.2). ORR (95% CI) for pts with measurable disease was 6% (2.6-11.5) in C1 and 3% (0.4-10.4) in C2 (Table; includes other efficacy results). Treatment-related AEs of any grade/grade 3-5 occurred in 57%/16% in C1, 60%/15% in C2, and 71%/17% in C3. 1 pt in each cohort died of a treatment-related AE (C1, sepsis; C2, unknown; C3, immune-related pneumonitis). Conclusions: With additional follow-up, pembro monotherapy continued to show antitumor activity and disease control in pts with RECIST-measurable and bone-predominant mCRPC previously treated with both NHA and docetaxel. Pts experienced durable responses. Safety was consistent with the known safety profile of pembro. Clinical trial information: NCT02787005. [Table: see text]

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