Virtual Library
Start Your Search
Kozo Kuribayashi
Author of
-
+
P1.14 - Thymoma/Other Thoracic Malignancies (Not CME Accredited Session) (ID 946)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
-
+
P1.14-19 - Hemagglutinating Virus of Japan Envelope (HVJ-E: Inactivated Viral Nanoparticles) Against Chemotherapy-Resistant Pleural Mesothelioma (ID 12248)
16:45 - 18:00 | Author(s): Kozo Kuribayashi
- Abstract
Background
Hemagglutinating virus of Japan envelope (HVJ-E) derived from inactivated replication-defective Sendai virus possess the various antitumor activities. HVJ-E enhances multiple antitumor immunities such as activation of dendritic cells, induction of natural killer cells and CTL, and suppression of regulatory T cells, and it induces direct tumor-killing by the induction of cell death through the RIG-I/MAVS pathway by direct administration into the tumor.
We performed the phase I dose escalation safety/tolerability and preliminary efficacy study of intra-tumoral and subcutaneous administration of HVJ-E in patients suffering from chemotherapy-resistant malignant pleural mesothelioma.
a9ded1e5ce5d75814730bb4caaf49419 Method
We performed the dose upward titration clinical study for checking the safety, drug tolerance, and preliminary efficacy of the intra-tumoral and subsequent subcutaneous administration of HVJ-E. We administrated HVJ-E to the patients 4 times per 2 weeks (the first was intra-tumoral, and residual 3 times were subcutaneous injection), and then washed out the drug from the body for 2 weeks. This cycle was repeated 2 times. We observed the patients for 8 weeks, and evaluated them by CTCAE, modified RECIST, and PERCIST.
4c3880bb027f159e801041b1021e88e8 Result
Three patients were enrolled as a low-dose group, and three patients were enrolled as a high-dose group. There was no discontinuation of the administration due to the severe adverse events.
Results;
The mean disease duration from confirmed diagnosis to this trial was 2.27 years (0.6-4.5 years). We defined the primary endpoint as an assessment of dose limiting toxicity related with HVJ-E. Neither serious adverse events (SAE) nor DLT were observed during the observation period. The following symptoms were observed. Fever (83.3%), and the local symptoms at injection site, for example, rubor, swelling, or induration (100%) were observed, but the local relapse of mesothelioma at the injection site was not observed. It was confirmed that the intra-tumoral and subcutaneous administration of HVJ-E was safe for chemotherapy-resistant pleural mesothelioma patients, because these AEs were transient and slight.
The efficacy as a secondary endpoint was evaluated with modified RECIST, and PERCIST. DCR of low dose level cohort was 0% (0/3), because of PD, meanwhile, high dose level cohort indicated 100% (3/3). Consequently, the DCR of all cases who had treated with HVJ-E was 50% (3/6) by mRECIST, meanwhile, the DCR evaluated by PERCIST was 100%.
8eea62084ca7e541d918e823422bd82e Conclusion
It was suggested that HVJ-E was useful for disease control of advanced pleural mesothelioma patients without severe adverse events. Now we do the next step trial for malignant pleural mesothelioma and melanoma with high dose of HVJ-E.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.01-112 - Prognostic Value of Changes in Neutrophil-To-Lymphocyte Ratio in Patients with Lung Cancer Treated with Nivolumab (ID 13715)
16:45 - 18:00 | Author(s): Kozo Kuribayashi
- Abstract
Background
Nivolumab, an anti-programmed cell death 1(PD-1) antibody, is a standard regimen for the second-line treatment of non-small cell lung cancer (NSCLC). However, compared with molecular-targeted drugs, the response rate to nivolumab is low, and biomarkers of efficacy are currently lacking. It has been recently reported that the neutrophil-to-lymphocyte ratio (NLR) can be a biomarker of efficacy. Here, we examined the possibility for NLR to predict efficacy of nivolumab.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively examined all patients with NSCLC who were treated with nivolumab at our institution.
4c3880bb027f159e801041b1021e88e8 Result
We compared 35 patients with NLR of ≥3 and 44 with NLR of <3, all of whom were treated with nivolumab. There was no difference in response rates between the two groups. The median (m) PFS and mOS were 130 and 583 days in the NLR≥3 group, whereas those were 169 days and not reached (NR) in the NLR<3 group. Longer PFS and OS were observed in the NLR<3 group than in the NLR≥3 group. Next, we analyzed the relationship between treatment efficacy and relative change of NLR (∆NLR), the ratio of the value at 4 weeks after the administration of nivolumab to the value at baseline. In 42 patients with ∆NLR of ≥1, mPFS and mOS were 122 and 564 days, respectively. In 31 patients with ∆NLR of <1, mPFS and mOS were 280 days and NR, respectively. PFS and OS were significantly better in the group with ∆NLR of <1. With respect to adverse events, grade 1-2 rashes were observed in 29% of patients in the group with ∆NLR of <1 and in 9.5% of patients in the group with ∆NLR of ≥1.
8eea62084ca7e541d918e823422bd82e Conclusion
Relative ratio of NLR at 4 weeks/at baseline is a predictive biomarker in patients with NSCLC who are treated with nivolumab.
6f8b794f3246b0c1e1780bb4d4d5dc53
-
+
P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.06-11 - A Phase I/II Study of Intrapleural Ad-SGE-REIC Administration in Patients with Refractory Malignant Pleural Mesothelioma (ID 11328)
16:45 - 18:00 | Author(s): Kozo Kuribayashi
- Abstract
Background
Reduced expression in immortalized cell (REIC)/Dickkopf-3 (Dkk-3) is a tumor-suppressor gene and REIC/Dkk-3 expression was markedly downregulated in various human cancer cells. REIC/Dkk-3 protein is also known as a key player, namely an antagonist of the Wnt signaling pathway. Ad-SGE-REIC is an adenoviral vector carrying REIC/Dkk-3 that mediates cancer cell death induction and anti-cancer immunity augmentation.
a9ded1e5ce5d75814730bb4caaf49419 Method
We conducted a phase I/II, 3+3 design, dose escalation study in malignant pleural mesothelioma (MPM) patients (pts) with measurable lesions. Pts with refractory to or unsuitable for standard chemotherapy received 2 intrapleural administrations of Ad-SGE-REIC on days1 and 4. Three escalating doses of level (DL) 1: 3.0×1011, DL2: 1.0×1012 and DL3: 3.0×1012 viral particles were employed. This dosage and regimen were set by considering the reason of manufacturing and neutralizing anti-body for adenovirus. The safety and dose-limiting toxicities (DLTs) of Ad-SGE-REIC were evaluated for 32 days. Continuous safety and efficacy were assessed for 172 days using modified RECIST (mRECIST). The concentrations of REIC/Dkk-3 in pleural fluid also were measured as indirect indication of targeted gene expressions.
4c3880bb027f159e801041b1021e88e8 Result
From 07/2015 to 09/2017, a total of 13 pts have been treated at DL1 (n=4 included one fatal case within 32 days), DL2 (n=3) and DL3 (n=6). Male: 100%; median age 70; PS 0: 23%, 1: 69%, 2: 8%; epithelial/biphasic histology: 69%/15%; Stage III-IV: 77%; previous chemotherapy use with platinum-pemetrexed: 92%. Treatment-related AEs (TRAEs) were all Grade 1-2 and no DLTs occurred. The most frequent TRAEs were fever and CRP increase based on adenovirus infection. Tumor responses assessed by independent central review showed that there was no objective response and DCR was 62% (8/13 pts). Median PFS was 3.4 months at all groups and 5.7 months at DL3. A remarkable increase of REIC/Dkk-3 concentration in pleural fluid was determined (6/13 pts, prominently high in DL3).
8eea62084ca7e541d918e823422bd82e Conclusion
The intrapleural administration of Ad-SGE-REIC up to 2 cycles was safe and well tolerated in MPM pts and promising results of efficient REIC/Dkk-3 expression and durable disease control were obtained. We are planning phase II study using repeated intrapleural or intratumoral administration.
6f8b794f3246b0c1e1780bb4d4d5dc53
