scholarly journals 44P Biomarker analysis from a phase Ib, multicenter, open-label clinical trial of talimogene laherparepvec (T-VEC) injected (inj) into metastatic and primary liver tumors

2021 ◽  
Vol 32 ◽  
pp. S1390-S1391
Author(s):  
J.R. Hecht ◽  
M. Peeters ◽  
M. Martin Jimenez ◽  
M. Pless ◽  
A. Cubillo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Liver Tumors ◽  
Talimogene Laherparepvec ◽  
Open Label ◽  
Phase Ib ◽  
Primary Liver Tumors ◽  
Biomarker Analysis

Toripalimab with nab-paclitaxel/gemcitabine as first-line treatment for advanced pancreatic adenocarcinoma: Updated results of a single-arm, open-label, phase Ib/II clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16213-e16213
Author(s):  
Ke Cheng ◽  
Wan-Rui Lv ◽  
Xiaofen Li ◽  
Bole Tian ◽  
Dan Cao
Keyword(s):  
Clinical Trial ◽  
Safety Profile ◽  
Combined Treatment ◽  
Line Treatment ◽  
First Line ◽  
Open Label ◽  
Phase Ib ◽  
Biomarker Analysis ◽  
Open Label Phase ◽  
First Line Treatment

e16213 Background: Currently nab-paclitaxel/gemcitabine (AG) is the standard first-line treatment for advanced pancreatic ductal adenocarcinoma (aPDAC), which is still needed to improve. The phase Ib/II study aiming to evaluate safety and efficacy of AG plus toripalimab, an anti-PD-1 monoclonal antibody, showed well tolerability and encouraging efficacy in aPDAC patients (preliminary data presented at 2020 ASCO). Here, we updated new results of this study. Methods: This was a single-arm, open-label, phase Ib/II clinical trial of AG with toripalimab as first-line treatment for aPDAC. Patients received toripalimab (240mg, Q3W), combined with AG (nab-paclitaxel 125 mg/m2, d1, d8 plus gemcitabine 1000 mg/m2, d1, d8) until the disease progresses/unacceptable toxicity or receiving toripalimab maintenance treatment. The primary objectives were safety and OS; the secondary objectives were ORR, DCR and PFS. Predictive biomarkers including MMR protein and PD-L1 expression, the tumor mutation burden (TMB) based on next-generation sequencing, genomic alteration signatures and the number of TILs were evaluated. Results: At data cutoff (Feb 3, 2021), 20 chemotherapy naïve aPDAC patients (female: 65.0%, median age: 55.5 years) with ECOG PS ≤ 2 were enrolled. Of the 17 evaluable patients, the ORR was 35.3%, the DCR was 82.4%, including 5 patients with PR and 1 patient with CR, respectively. 12 patients were alive and the study treatments for 9 patients were still ongoing. Median PFS was 5.0 months (95% CI：4.216-5.784), the 6-month PFS rate was 60%; median OS was 14.0 months (95% CI：9.445-18.555), the 1-year OS rate was 80%. 2 cases of pseudoprogression were observed. The most frequent treatment related adverse events were ALT elevation (35.0%), leukocytopenia (30.0%) metabolic disorder (25.0%) and hypothyroidism (25.0%). 4 patients (20.0%) experienced grade 3/4 TRAE (including myocardial enzyme elevation, neutropenia, vomiting and nausea). In the biomarker analysis, all patients were MMR-proficient status; 14 patients were evaluated for PD-L1 expression compared with PD-L1 negative cases (n = 5), PD-L1 positive cases (n = 9) did not show higher RR or longer PFS, responses were observed in both groups. 10 patients were investigated for NGS, 2 patients with TMB > 10 Muts/Mb, the most frequently mutated genes were KRAS (90%), TP53 (90%) and ARID1A (20%). Conclusions: The updated results of this phase Ib/II study provided preliminary evidence that toripalimab in combination with AG has a manageable safety profile consistent with known safety profile for each agent alone and demonstrates signals of clinical activity. The correlation between biomarkers with clinical efficacy are under investigation. The results supported ongoing combined treatment in aPDAC patients. Clinical trial information: ChiCTR2000032293.

Early safety from a phase 1, multicenter, open-label clinical trial of talimogene laherparepvec (T-VEC) injected into liver tumors.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 438-438 ◽  
Author(s):  
J. Randolph Hecht ◽  
Miklos Pless ◽  
Antonio Cubillo ◽  
Aitana Calvo ◽  
Steven Raman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Liver Tumors ◽  
Disease Incidence ◽  
Phase 1 ◽  
Cell Cancer ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Open Label ◽  
Dose Escalation Study ◽  
Grade 3

438 Background: T-VEC is a genetically modified HSV-1 oncolytic immunotherapy designed to preferentially replicate in tumors, produce GM-CSF, and stimulate anti-tumor immune responses. This study evaluates the safety of intrahepatic injection (inj) of T-VEC in patients (pts) with hepatocellular carcinoma (HCC) or liver metastases (mets). Methods: The primary objective is to assess the maximum tolerated dose. Eligible pts were ≥ 18 years (y) old, had progressive HCC or breast cancer (BC), colorectal cancer (CRC), gastroesophageal cancer, melanoma, non-small cell lung cancer, or renal cell cancer with liver mets, with measurable liver tumors suitable for inj. This dose escalation study comprised 2 groups: A (non-HCC) and B (HCC). T-VEC was given initially at 106 plaque-forming units (PFU)/mL followed by up to 4 mL of 107 PFU/mL (cohort 1) or 108 PFU/mL (cohort 2) every 21 (±3) days (Q21D), or up to 8 mL of the maximum tolerated concentration (MTC) Q21D (cohort 3). Inj volume was based on lesion size. Results: Results from cohorts 1 and 2 of group A are reported. 14 pts were treated; 12 (3 BC, 9 CRC) were DLT-evaluable: Median age was 65.5 y (range: 33, 73); median number of inj was 3; 1 pt received all 12 inj. MTC was 108 PFU/mL. There was 1 DLT, grade 3 aspartate aminotransferase (AST)/grade 2 bilirubin increase (inc), after 1 dose. In all treated pts, 4 (28.6%) had grade 3/4 treatment-related adverse events (TRAEs): anemia and inc gamma-glutamyltransferase, alanine aminotransferase (ALT), and AST. There were 2 deaths attributable to disease. Incidence of serious AEs (SAEs) is shown (Table). Conclusions: The MTC was 108 PFU/mL Q21D after initial inj at 106 PFU/mL. Repeated intrahepatic inj of T-VEC at the FDA-approved concentration for intralesional inj of melanoma was deemed tolerable and feasible in pts with liver mets. Additional investigation in combination with a PD-1 inhibitor is planned. Clinical trial information: NCT02509507. [Table: see text]

scholarly journals A Phase I, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec (T-VEC) injected into liver tumors

2015 ◽  
Vol 3 (S2) ◽  
Author(s):  
J Randolph Hecht ◽  
Steven Raman ◽  
Daniel Y Sze ◽  
A Craig Lockhart ◽  
Rebecca A Moss ◽  
...  
Keyword(s):  
Phase I ◽  
Liver Tumors ◽  
Talimogene Laherparepvec ◽  
Open Label ◽  
Open Label Trial

Updated interim analysis of UCI 09-53: A phase II, single arm study of pazopanib and paclitaxel as first-line treatment for subjects with unresectable advanced melanoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9082-9082
Author(s):  
Shlomit Y. Ein-Gal ◽  
Walter Tsang ◽  
Beverly Alger ◽  
Basmina Parmakhtiar ◽  
James G. Jakowatz ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Interim Analysis ◽  
Cell Cancer ◽  
First Line ◽  
Open Label ◽  
Melanoma Tumor ◽  
Biopsy Material ◽  
Biomarker Analysis

9082 Background: Metastatic melanoma lacks effective therapy. Pazopanib is an inhibitor of VEGFR-1,2,3, PDGFR-B and c-KIT that has antiangiogenic activity in renal cell cancer as well as inhibition of melanoma tumor xenografts. We designed a phase II single arm, open label clinical trial evaluating pazopanib in combination with metronomic paclitaxel as first line therapy for subjects with unresectable stage III and stage IV melanoma. Methods: This protocol utilizes a Simon 2-stage Minimax design, with a planned interim analysis to confirm >3 responders to move to the second stage. To date, 31 patients are evaluable for response. All subjects were treatment naïve and received paclitaxel at 80mg/m2 weekly for three weeks in a 4 week cycle and pazopanib 800mg continuous daily oral dose. The primary endpoint is 6 month progression free survival. Exploratory endpoints include biomarker analysis that may be associated with treatment outcomes (serum VEGF, soluble VEGFR-2, serum HIF, serum TSP1 and BRAF mutation status). An additional exploratory endpoint includes the in vitro activity of pazopanib and paclitaxel on patient biopsy material co-cultured with vascular endothelial cells. RECIST 1.1 criteria were used to define treatment response (SD criteria was a minimum interval of 8 weeks). Results: For the 31 evaluable patients treated to date the following results were seen: 1 CR, 9 PR’s, 13 SD’s and 8 PD’s. The overall RR (CR+PR) was 32%. Total disease control rate was 74% (CR+PR+SD). The most common AEs/lab abnormalities were diarrhea (66%) nausea (60%), hypertension (63%), fatigue (63%) and vomiting (29%). Grade 3-4 AEs included hypertension (26%), transaminitis (23%) and neutropenia (17%).One patient discontinued for grade 4 transaminitis which subsequently resolved completely. Dose reductions were required for pazopanib in 15 patients and for paclitaxel in 4 patients. Conclusions: Updated interim analysis of this phase II study demonstrated that pazopanib in combination with paclitaxel was well tolerated and resulted in a 32% response rate, indicating that this combination is of further interest. Accrual will continue to reach a goal of 60 patients. Clinical trial information: NCT01107665.

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