scholarly journals A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Megumi Kai ◽  
Angela N. Marx ◽  
Diane D. Liu ◽  
Yu Shen ◽  
Hui Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Injection Site Reaction ◽  
Progression Free Survival ◽  
Median Number ◽  
Talimogene Laherparepvec ◽  
Distant Disease ◽  
Best Response ◽  
Common Grade ◽  
Number Of Cycles

AbstractTalimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3–8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63–NA) and 361 days (95% CI, 240–NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

scholarly journals A Phase II Study of Talimogene Laherparepvec for Patients With Inoperable Locoregional Recurrence of Breast Cancer

2021 ◽  
Author(s):  
Megumi Kai ◽  
Angela N. Marx ◽  
Diane D. Liu ◽  
Yu Shen ◽  
James M. Reuben ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Progression ◽  
Locoregional Recurrence ◽  
Injection Site Reaction ◽  
Progression Free Survival ◽  
Median Number ◽  
Talimogene Laherparepvec ◽  
Best Response ◽  
Registration Number ◽  
Number Of Cycles

Abstract Purpose: Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer.Methods: Patients had to have cutaneous, subcutaneous, or nodal tumors injectable with T-VEC. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥3). Local lesions were photographed before each cycle.Results: Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n=7, 78%).Conclusion: None of the patients was able to complete the planned 10 cycles due to the disease progression. Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.Trial registration number and date of registration: ClinicalTrials.gov Identifier: NCT02658812; registered [January 14, 2016]

scholarly journals Phase I clinical trial of the combination of eribulin and everolimus in patients with metastatic triple-negative breast cancer

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin Sun Lee ◽  
Susan E. Yost ◽  
Suzette Blanchard ◽  
Daniel Schmolze ◽  
Hongwei Holly Yin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Dose Level ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Median Number ◽  
Primary Objective ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background Alteration of the PI3K/AKT/mTOR pathway is a common genomic abnormality detected in triple-negative breast cancer (TNBC). Everolimus acts synergistically with eribulin in TNBC cell lines and xenograft models. This phase I trial was designed to test the safety and tolerability of combining eribulin and everolimus in patients with metastatic TNBC. Methods The primary objective of this study was to evaluate the safety and toxicities of the combination. Patients with metastatic TNBC who had up to four lines of prior chemotherapies were enrolled. The combination of eribulin and everolimus was tested using three dosing levels: A1 (everolimus 5 mg daily; eribulin 1.4 mg/m2 days 1 and 8 every 3 weeks), A2 (everolimus 7.5 mg daily; eribulin 1.4 mg/m2, days 1 and 8 every 3 weeks), and B1 (everolimus 5 mg daily; eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks). Results Twenty-seven patients with median age 55 years were enrolled. Among 8 evaluable patients who received dose level A1, 4 had dose-limiting toxicities (DLTs). Among 3 evaluable patients treated with dose level A2, 2 had DLTs. Among 12 evaluable patients who received dose level B1, 4 had DLTs. The DLTs were neutropenia, stomatitis, and hyperglycemia. Over the study period, 59% had a ≥ grade 3 toxicity, 44% had ≥ grade 3 hematologic toxicities, and 22% had grade 4 hematologic toxicities. The most common hematological toxicities were neutropenia, leukopenia, and lymphopenia. Thirty-three percent had grade 3 non-hematologic toxicities. The most common non-hematological toxicities were stomatitis, hyperglycemia, and fatigue. The median number of cycles completed was 4 (range 0–8). Among 25 eligible patients, 9 patients (36%) achieved the best response as partial response, 9 (36%) had stable disease, and 7 (28%) had progression. The median time to progression was 2.6 months (95% CI [2.1, 4.0]), and median overall survival (OS) was 8.3 months (95% CI [5.5, undefined]). Conclusion Eribulin 1.1 mg/m2 days 1 and 8 every 3 weeks with everolimus 5 mg daily was defined as the highest dose with acceptable toxicity (RP2D). The combination is safe, and efficacy is modest. A post hoc analysis showed that participants that used dexamethasone mouthwash stayed on treatment for one additional cycle. Trial registration ClinicalTrials.gov, NCT02120469. Registered 18 April 2014

Topotecan plus carboplatin versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabin plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC): A randomized phase III trial of the NOGGO-AGO-Germany-AGO Austria and GEICO-GCIG intergroup study (HECTOR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5031-5031 ◽  
Author(s):  
Jalid Sehouli ◽  
Werner Meier ◽  
Pauline Wimberger ◽  
Radoslav Chekerov ◽  
Antje Belau ◽  
...  
Keyword(s):  
Standard Therapy ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Platinum Sensitive ◽  
Best Response ◽  
Phase Iii Study ◽  
Number Of Cycles

5031 Background: We present the efficacy data from a phase III study of topotecan (T) plus carboplatin (C) versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC). Methods: From 02/07 to 12/09, 590 pts were screened and 550 pts were randomized to either T (0.75mg/m²/d1-3/q21d) + C (AUC 5/d1/q21d) or to standard therapy with CP or GC or PLDC based on patient preference. Progression free survival at 1 year was defined as primary endpoint. Results: Median number of cycles was 6 (range 0-9) in both arms. Most patients preferred GC (78%) in the standard therapy arm.. Best Response (CR+PR) was 73.1% (95%CI) and 75.1% (95%CI) for the CA. Median follow-up was 18 (0-52) months for TC and 20 (0-48) months for standard therapy. TC failed to show any advantage regarding 1-yr.-PFS or OAS. Conclusions: The combination of topotecan plus carboplatin failed to improve PFS or OAS in platinum sensitive relapsed ovarian cancer. In addition, carboplatin plus gemcitabine was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities compared to paclitaxel-carboplatin. [Table: see text]

scholarly journals Glembatumumab vedotin for patients with metastatic, gpNMB overexpressing, triple-negative breast cancer (“METRIC”): a randomized multicenter study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Linda T. Vahdat ◽  
Peter Schmid ◽  
Andres Forero-Torres ◽  
Kimberly Blackwell ◽  
Melinda L. Telli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Primary Endpoint ◽  
Triple Negative ◽  
Progression Free Survival ◽  
Antibody Drug Conjugate ◽  
Open Label ◽  
Common Grade ◽  
Open Label Phase ◽  
Grade 3

AbstractThe METRIC study (NCT#0199733) explored a novel antibody–drug conjugate, glembatumumab vedotin (GV), targeting gpNMB that is overexpressed in ~40% of patients with triple-negative breast cancer (TNBC) and associated with poor prognosis. The study was a randomized, open-label, phase 2b study that evaluated progression-free survival (PFS) of GV compared with capecitabine in gpNMB-overexpressing TNBC. Patients who had previously received anthracycline and taxane-based therapy were randomized 2:1 to receive, GV (1.88 mg/kg IV q21 days) or capecitabine (2500 mg/m2 PO daily d1–14 q21 days). The primary endpoint was RECIST 1.1 PFS per independent, blinded central review. In all, 327 patients were randomized to GV (213 treated) or capecitabine (92 treated). Median PFS was 2.9 months for GV vs. 2.8 months for capecitabine. The most common grade ≥3 toxicities for GV were neutropenia, rash, and leukopenia, and for capecitabine were fatigue, diarrhea, and palmar-plantar erythrodysesthesia. The study did not meet the primary endpoint of improved PFS over capecitabine or demonstrate a relative risk/benefit improvement over capecitabine.

Efficacy and Safety of Denileukin Diftitox (Ontak®) in the Treatment of Cutaneous T-Cell Lymphoma (CTCL) According to CD25 Status.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2712-2712 ◽  
Author(s):  
Francine Foss ◽  
Madeleine Duvic ◽  
Larisa Geskin ◽  
Joseph Anderson ◽  
Pierluigi Porcu ◽  
...  
Keyword(s):  
Response Rate ◽  
Interleukin 2 ◽  
Median Number ◽  
Open Label ◽  
Denileukin Diftitox ◽  
Common Grade ◽  
Stage Ivb ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Multi Center Study

Abstract Denileukin diftitox, an interleukin-2 (IL-2)-diphtheria toxin fusion protein, binds to and intoxicates cells expressing the medium (CD122, CD132) and high affinity (CD25, CD122, CD132) IL-2 receptor. Because its role in patients whose tumors tested negative for the CD25 component of the receptor had not been prospectively studied, we initiated a prospective, open label, multi-center study to evaluate the safety and efficacy of denileukin diftitox in CTCL patients according to CD25 status (CD25+ and CD25-). Patients with pathologically proven, persistent or recurrent CTCL Stages IB-IVA were treated with denileukin diftitox at a dose of 18 mcg/kg/day x 5 days every 21 days for up to 8 cycles. Expression of CD25 by tumor cells in skin biopsies was determined by IHC or flow cytometry at a central laboratory and investigators were blinded to CD25 status. Response was based on improvement in skin involvement by weighted skin assessment for lesion type (patch, plaque, tumor) and blood involvement based on quantitation of Sezary cells. Safety was evaluated based on reports of Grade 3 and 4 toxicities (NCI CTC version 2.0). Sixty-one pts were enrolled and treated with denileukin diftitox. Disease stages were: I-IIA (n=14), IIB (n=22), III (n=11) and IV (n=14). Eighteen (29.5%) had blood involvement. Fifty-seven pts completed at least one cycle of treatment and were evaluable for response. Four pts were excluded because they had Stage IVB (visceral) disease (n=2), did not have a post baseline skin assessment recorded (n=1), or did not complete the first cycle (n=1). The median number of cycles of denileukin diftitox was 4 (range 1–13). The overall response rate (CR+PR) was 53% (30/57, 95% CI 40–66%), with 2 CR. Of the 57 evaluable pts, tumor was CD25+ in 34 (70%), CD25- in 14 (25%) and unknown in 9. Response rate was similar in patients whose tumor tested CD25+ (56%, 95% CI: 39–73%), and CD25- (43%, 95% CI: 17–69%) (p=0.41). For the 61 patients the most common grade 3/4 toxicities included constitutional symptoms (11%) and metabolic/laboratory abnormalities (36%). One patient with significant cardiopulmonary disease died of myocardial infarction while on therapy. The frequency of grade 3/4 toxicities was similar in CD25+ 64% (23/36), vs CD25- 75% (12/16) (p=0.62). In conclusion, we found that 70% of the CTCL pts evaluated for this study tested CD25+ and that the response rates and safety profile of denileukin diftitox in CD25+ and CD25- patients were similar. These data support a role for denileukin diftitox in the treatment of CTCL regardless of CD25 status.

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15111-15111 ◽  
Author(s):  
Y. Park ◽  
S. Yi ◽  
H. Kim ◽  
S. Lee ◽  
I. Hwang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stable Disease ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
Best Response ◽  
Grade 3 ◽  
Number Of Cycles

15111 Background: The aim of this phase II study was to determine whether second line therapy with single agent irinotecan could provide any clinical benefit in patients with gemcitabine- pretreated advanced pancreatic cancer. Methods: From January 2004 to October 2006, patients with advanced pancreatic cancer previously treated with gemcitabine alone or combination were treated with single agent irinotecan(150 mg/m2, biweekly), until unacceptable toxicity or disease progression. Primary endpoint was response rate with single stage design. Results: Twenty-eight patients were enrolled(22 male, 6 female, median age : 54.5 years (39–76)). Nine patients are still alive and 3 remain on therapy with stable disease. The median number of cycles was 3.5(1–12). Twenty-four patients were assessable for toxicity and 21 for response. The most common toxicities was diarrhea (grade 3, 12.5%). Grade 3 neutropenia in 1 patient was observed. Other hematological and non-hematological toxicities were mild and manageable. Partial responses were observed in 3 patients (3/21, 14%). An additional 9 patients (9/21, 43%) had stable disease as their best response. 12 patients have progressed with a median time-to-progression of 4.0 months. Conclusions: Single-agent irinotecan was tolerated with manageable toxicity, offering encouraging activity as second-line treatment of patients with advanced pancreatic cancer, refractory to gemcitabine. No significant financial relationships to disclose.

Phase II dose escalation study of sorafenib in patients with metastatic renal cell carcinoma (mRCC) who have had prior treatment with VEGFR-TKI antiangiogenic treatment

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16027-e16027
Author(s):  
A. P. Mancuso ◽  
E. Donato De Paola ◽  
A. Catalano ◽  
F. Calabrò ◽  
C. Messina ◽  
...  
Keyword(s):  
Standard Dose ◽  
Progression Free Survival ◽  
Median Number ◽  
Dose Escalation Study ◽  
Multikinase Inhibitor ◽  
Prior Therapy ◽  
Hand Foot Syndrome ◽  
Tki Treatment ◽  
Number Of Cycles ◽  
Metastatic Sites

e16027 Background: Sorafenib is an orally active multikinase inhibitor (Raf kinase, VEGFR 1, 2, 3 and PDGFR inhibitor) for the treatment of advanced RCC. The purpose of this study was to assess the efficacy and toxicity of Sorafenib in mRCC patients (pts) previously treated with an anti-angiogenic VEGFR-TKI using escalating dose levels. Methods: Pts with mRCC, PS 0–2 and adequate organ function were eligible. Pts received Sorafenib 400 mg/BID/continuously in 4-wk cycles. Pts with no progressive disease (evaluated at 12 weeks) continued to receive Sorafenib at the standard dose, while progressive pts received an increasing dose (600 mg BID) with early disease restaging after 4 weeks. Pts who progressed at 600 mg BID were taken off study. Efficacy was assessed by RECIST criteria. Results: 18 pts were entered; baseline characteristics: PS 0–1: 94%; median age 62 years (41–82); nephrectomy: 100%; surgery for metastatic disease: 28%, clear-cell 78%, papillary-cell 16%, sarcomatoid 6%.≥ 2 metastatic sites: 84%. 10 pts were refractory to cytokine treatment and all progressed or experienced unacceptable toxicity after anti-angiogenic VEGFR-TKI treatment, Sunitinib (13 pts) or Pazopanib (5 pts). Median number of cycles was 7.5 (1–16). Overall, 72% of pts had disease control without significant correlations between response to prior therapy and hypertension. 14 pts had progression free survival (PFS) of 4.3 months (mos). 4 pts are still in treatment with a median PFS > 8 mos. Of 6 pts in which the dose was escalated, 3 benefitted with a PFS of > 3 mos. The most common toxicity (NCIC 3.0, all pts) was grade (g) ≥ 1 diarrhea in 10 pts, g2–3 hand-foot syndrome in 7 pts and g-3 mucositis in 1 pt. Other hematological and non-hematological toxicities were g1 with a frequency < 15%. Conclusions: Sorafenib at doses of 400–600 mg/BID/continuosly results in acceptable and well tolerated salvage treatment after VEGFR-TKI failure. In progressive patients, treatment with a higher dose could be a valid option. Final and mature data will be presented in combination with translational research evaluating biological characteristics on tissue and blood. No significant financial relationships to disclose.

Neoadjuvant chemotherapy for locally advanced cervical cancer: Experience at the Instituto Oncologico Nacional SOLCA Guayaquil.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15571-e15571
Author(s):  
Guillermo Paulson ◽  
Katherine Garcia ◽  
Mayra Santacruz ◽  
Ruth Ginger Engracia ◽  
Jose Francisco Mendoza
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Invasive Cervical Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Median Number ◽  
Number Of Cycles ◽  
Clinical Records ◽  
Cancer Experience

e15571 Background: Cervical cancer is the most common malignancy of women in Ecuador. The main problem of concomitant chemo-radiotherapy (CRT) is the delay in starting radiation therapy, economic and logistical problems for high demand in radiotherapy. It has been neoadjuvant chemotherapy (NACT) followed by CRT the main treatment at our center in order to find an alternative to long waits before the start of radiotherapy. The aim of this study was to determine the response to NACT followed by CRT in terms progression-free survival (PFS) and overall survival (OS). Methods: diagnosed with invasive cervical cancer locally advanced stage II-III were analyzed retrospectively reviewed clinical records of pre-existing data from 2008 to 2010. Results: after meeting the criteria of exclusion, leaving 116 cases. The median age: 49 years (range: 28-82 years). The histology was 73% (85) squamous cell carcinoma, 26% (30) adenocarcinoma and 0.9% (1) not specified. Patients with stage IIB: 81.9% (95), IIIA: 10.3% (12), IIIB: 7.8% (9). Of the 116 patients 69% (80) received NACT. The main NACT was paclitaxel 175mg/m2 + Cisplatin 75mg/m2 every 3 weeks 63.8% (74), the remaining group received another protocol, the median number of cycles of NACT was 5 (1 - 8 cycles), the start of radiotherapy since the conclusion of NACT was 53 days on average (1 to 285 days) and the main regimen of CRT concomitant was cisplatin 40mg/m2 weekly 47.5% (38). In the 49 patients who underwent NACT followed by CRT, a radiological study showed, complete response (CR) 38.8% (19), 18.4% partial response (PR) (9), disease progression (DP) 12.2% (6), stable disease (SD) 8.2% (4) and the end of treatment evaluation gynecological was performed and CR was obtained in 59.2% (29). Persistent or progressive disease after treatment was 22.4% (11), recurrence was 12.2% (6), local recurrence 2.0% (1), distant metastasis 10.2% (5). OS of NACT followed by CRT was 93.9% (46) and PFS was 65.3% (32), OS after CR was 96% (25 / 1) and then 91.7% PR (24 / 2) with p: 0.439. Conclusions: NACT followed by CRT is a valid option because it improves disease-related symptoms, but OS did not improve significantly even after CR.

Phase I trial of sunitinib (S) and temsirolimus (T) in metastatic renal cell carcinoma (mRCC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 433-433
Author(s):  
Matthew T. Campbell ◽  
Randall E. Millikan ◽  
Emre Altinmakas ◽  
Lianchun Xiao ◽  
Nizar M. Tannir
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Mtor Inhibitors ◽  
Median Number ◽  
Primary Objective ◽  
Best Response ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Mean Time

433 Background: Anti-VEGF agents and mTOR inhibitors are mainstay therapies in mRCC. Pre-clinical data suggests synergistic anti-tumor effect when combining these 2 classes. A previous phase I trial using sunitinib (S) 25 mg/d 4 wks on, 2 wks off, and temsirolimus (T) 15 mg/wk was stopped after 2 of the first 3 pts developed dose limiting toxicity (DLT). Methods: Pts with any subtype mRCC (PS 0-1) were eligible. Each cycle consisted of daily S for 14 days on, 7 days off, and weekly T. The continuous reassessment method (CRM) was used. The primary objective was to find the maximum tolerated doses (MTD) of S and T. The total planned accrual was 60 pts. Results: Accrual was stopped after 20 pts received study drugs. Median age was 63.5 years; 13 pts received prior targeted therapy, 7 pts were treatment naïve; median number of prior treatments 1 (range 0-6). Treatment cohorts (#pts, S, T, dose in mg): 2 (S12.5,T6), 1 (S25,T12.5), 1 (S12.5,T8), 8 (S12.5alt25,T9), 2 (S25,T6), 2 (S25alt37.5,T6), 2 (S37.5,T6), 2 (S37.5,T8). Dose reduction was required in 6 of 20 pts; the most common DLT was mucositis in 3 of 20 pts, followed by thrombocytopenia in 2 of 20 pts. The mean number of cycles for all pts was 6.6±5.36, with mean time on study 159±120 days. One pt experienced DLT in cycle 1 and received no study related imaging, 1 had a partial response, 16 pts had stable disease, and 2 pts had progressive disease (PD) as best response. A total of 21 grade 3/4 adverse events (AEs) attributed to drug occurred in 11 of 20 pts. Reasons for study discontinuation were PD in 12 pts, toxicity in 6 pts, and pt preference in 2 pts. There were no treatment related deaths. Conclusions: The MTD of S and T using the CRM were not reached due to premature trial closure. However, we believe S 37.5 mg/d, 2 wks on, 1 wk off, and T 8-10 mg weekly may well be close to MTD. Clinical trial information: NCT01122615.

Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5038-5038 ◽  
Author(s):  
Michael J. Morris ◽  
Nicholas J. Vogelzang ◽  
Oliver Sartor ◽  
Alison Armour ◽  
Michael Groaning ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Median Number ◽  
Selection Strategy ◽  
Microtubule Inhibitor ◽  
Normal Tissues ◽  
Castrate Resistant ◽  
Number Of Cycles ◽  
Spect Scan

5038 Background: Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, but not in most normal tissues, making it a potential therapeutic target. We are conducting a two-part phase 1 dose escalation/expansion study of EC1169, a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide in mCRPC. The utility of the PSMA-targeted companion imaging agent 99mTc-EC0652 is also being evaluated as a patient selection tool. The safety, efficacy, and imaging-based PSMA selection strategy are being investigated in Part A (dose escalation) and Part B (2-stage, 2-cohort expansion). Methods: Part A pts were eligible if they progressed on abiraterone or enzalutamide, and were treated with a taxane. EC1169 was administered as an IV bolus on days 1, 8 every 21 days. Part B pts are enrolled in 1 of 2 cohorts, mCRPC taxane naïve (cohort 1, 45 pts) and taxane exposed (cohort 2, 40 pts). Prior to treatment, pts undergo a 99mTc-EC0652 SPECT scan. The primary endpoint of Part B is median radiographic progression-free survival (rPFS). Other study evaluations are OS, PSA, and CTC-based biomarkers. Results: Part A is now complete: the RP2 dose is 6.5 mg/m2, on the basis of non-DLT transaminitis. 20 Part A/B pts have been treated at the RP2 dose (7 taxane naïve, 13 taxane exposed). Median age is 69 (range: 59-82). Median number of cycles is 2 (range: 1-7). 10 pts (50%) reported at least 1 treatment related AE. Most treatment related AEs are Gr1 and 2; G3 thrombocytopenia, fatigue, and constipation have occurred in 1 pt each. No Grade 4 treatment related AEs have been reported. No DLT or toxicity requiring dose reductions occurred. Four taxane-exposed pts in Part B have reached their first 9 wk radiographic assessment, of which two have soft tissue disease. One of those two patients (50%) has achieved an unconfirmed RECIST PR. Conclusions: The RP2 dose of EC1169 is 6.5 mg/m2. EC1169 has been well tolerated in 20 pts at the RP2 dose. Imaging with 99mTc-EC0652 suggests excellent disease localization supporting a PSMA-targeted therapeutic strategy. There is evidence of anti-tumor activity in both the dose escalation and expansion cohorts. Clinical trial information: NCT02202447.

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