Phase I study of liposomal irinotecan (LY01610) in patients with advanced esophageal squamous cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16097-e16097
Author(s):  
Yun Liu ◽  
Bo Zhang ◽  
Jianping Xu ◽  
Xingyuan Wang ◽  
Jialin Tang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dose Escalation ◽  
Prolonged Exposure ◽  
Single Agent ◽  
Complete Response ◽  
Maximum Tolerated Dose

e16097 Background: This phase I trial was performed to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), preliminary efficacy, and pharmacokinetics (PK) of LY01610, a novel liposome-encapsulated irinotecan, in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods: This trial was conducted in two stages. In the dose-escalation stage, patients with advanced ESCC refractory or intolerant to previous chemotherapy received escalating doses of LY01610. A recommended dose based on patient tolerance was then expanded in the second stage. LY01610 was administered intravenously every 2 weeks, except that the first cycle in dose-escalation was three weeks to allow observation of DLTs. Results: Twenty-four patients were enrolled across four dose levels (30, 60, 90 and 120 mg/m2). The DLTs included vomiting and febrile neutropenia, and the MTD was 90 mg/m2. The most common grade 3/4 adverse events were leukopenia in six patients (25.0 %), anemia in six patients (25.0 %) and neutropenia in five patients (20.8 %). One patient achieved complete response, and four had partial response, including one patient receiving LY01610 at the starting dose of 30 mg/m2. Compared with conventional irinotecan, the PK profile of LY01610 was characterized by increased and prolonged exposure of total irinotecan and the active metabolite SN-38 in plasma. Conclusions: LY01610 demonstrated manageable toxicity and promising antitumor activity in patients with advanced ESCC. Future clinical development of LY01610 as single agent or in combination with other anti-cancer agents in treating ESCC patients is warranted. Clinical trial information: NCT04088604.

800 A phase I dose escalation and expansion study of intratumorally administered CV8102 as a single-agent or in combination with anti-PD-1 antibodies in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A849-A849
Author(s):  
Thomas Eigentler ◽  
Lucie Heinzerling ◽  
Jürgen Krauss ◽  
Carsten Weishaupt ◽  
Peter Mohr ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Adenoid Cystic Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Dose Escalation ◽  
Single Agent ◽  
List Type ◽  
Adenoid Cystic

BackgroundCV8102 is a non-coding, non-capped RNA complexed with a carrier peptide activating the innate (via TLR7/8, RIG-I) and adaptive immune system.1 2 An ongoing phase I trial is investigating i.t. CV8102 either as a single agent or in combination with systemic anti-PD-1 antibodies in patients with advanced melanoma (MEL), squamous cell carcinoma of the skin (cSCC) or head and neck (hnSCC) and adenoid cystic carcinoma (ACC).MethodsAn open-label, cohort-based, dose escalation and expansion study in patients with advanced cutaneous melanoma (cMEL), cutaneous squamous cell carcinoma (cSCC), head and neck squamous cell carcinoma (hnSCC) or adenoid cystic carcinoma (ACC) is ongoing investigating i.t. CV8102 as single agent and in combination with anti-PD-1 antibodies.8 intratumoral injections of CV8102 are being administered initially over a 12 week period, while patients benefiting from the single agent therapy may receive further treatment. In an initial dose escalation part the maximum tolerated dose and recommended phase 2 dose for subsequent cohort expansion will be defined.ResultsAs of September 16, 2020, 29 patients have been treated with CV8102 as a single agent (25-900 µg) and 21 patients have received CV8102 (25-900 µg) in combination with anti-PD-1 antibodies. Most frequent treatment related adverse events were mild to moderate fever, fatigue, chills and headache. One patient treated at the 900 µg single agent experienced a dose limiting toxicity (G3 transaminase increase in the context of G2 cytokine release syndrome).Regression of injected and distant noninjected lesions was observed in several patients in the single agent and the anti-PD-1 combination cohorts. Updated safety and efficacy results will be presented.ConclusionsCV8102 showed an acceptable tolerability and preliminary evidence of clinical efficacy as single agent and in combination with anti-PD-1- antibodies.Trial RegistrationNCT03291002Ethics ApprovalThe study was approved by the Central Ethics Committees in Tuebingen, Germany under 785/2016AMG1, in France under 19.05.17.64111, in Barcelona, Spain under the EudraCT number.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.ReferencesZiegler A, Soldner C, Lienenklaus S, Spanier J, Trittel S, Riese P, Kramps T, Weiss S, Heidenreich R, Jasny E, Guzmán CA, Kallen KJ, Fotin-Mleczek M, Kalinke U. A new RNA-based adjuvant enhances virus-specific vaccine responses by locally triggering TLR- and RLH-dependent effects. J Immunol 2017;198(4):1595-1605. doi:10.4049/jimmunol.1601129Heidenreich R, Jasny E, Kowalczyk A, Lutz J, Probst J, Baumhof P, Scheel B, Voss S, Kallen KJ, Fotin-Mleczek M. A novel RNA-based adjuvant combines strong immunostimulatory capacities with a favorable safety profile. Int J Cancer 2015 Jul 15;137(2):372-84. doi: 10.1002/ijc.29402

scholarly journals Phase I/II Study of Docetaxel/Cisplatin/Fluorouracil Combination Chemotherapy Against Metastatic Esophageal Squamous Cell Carcinoma

2010 ◽  
Vol 5 (1) ◽  
pp. 122-128 ◽  
Author(s):  
Hiroaki Takahashi ◽  
Yoshiaki Arimura ◽  
Kentaro Yamashita ◽  
Satoshi Okahara ◽  
Tokuma Tanuma ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Combination Chemotherapy

scholarly journals Phase I Trial of Copanlisib, a Selective Pi3k Inhibitor, in Combination With Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Grégoire Marret ◽  
Nicolas Isambert ◽  
Keyvan Rezai ◽  
Jocelyn Gal ◽  
Esma Saada-Bouzid ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Maximum Tolerated Dose ◽  
Pi3k Inhibitor ◽  
Neck Squamous Cell Carcinoma ◽  
Best Response ◽  
Disease Stabilization

Abstract BackgroundThe phosphatidylinositol-3 kinase pathway is often altered in head and neck squamous cell carcinoma (HNSCC), and is involved in the resistance to EGFR inhibitors. ObjectiveWe investigated the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetics, and preliminary efficacy of the combination of copanlisib, an intravenous, pan-class I PI3K inhibitor, with the anti-EGFR monoclonal antibody cetuximab in recurrent and/or metastatic HNSCC patients in a phase I dose-escalation trial. Patients and methodsCopanlisib was given intravenously on days 1, 8, and 15 of 28-day cycles at the dose of 45 mg and 30 mg, in combination with standard doses of weekly cetuximab (400 mg/m² loading dose followed by 250 mg/m² on days 8, 15, and 22, and weekly thereafter). ResultsThree patients received copanlisib 45 mg, of whom two experienced grade 3 hyperglycemia during Cycle 1 that met the DLT criteria. Eight patients were then treated with copanlisib at the dose of 30 mg. Because of the occurrence of hyperglycemia, a premedication with metformine was introduced on the day of the injections. No DLTs were reported at this dose level. The trial was stopped early because of the unfavourable toxicity profile of the combination. Among eight evaluable patients for response, four patients (50%) had disease stabilization according to RECIST1.1 as best response.ConclusionCopanlisib combined with cetuximab demonstrated unfavorable toxicity and limited efficacy in heavily pretreated recurrent and/or metastatic HNSCC patients. NCT02822482, Date of registration: June 2016.

Late toxicity in complete response cases after definitive chemoradiotherapy for esophageal squamous cell carcinoma

2006 ◽  
Vol 41 (5) ◽  
pp. 425-432 ◽  
Author(s):  
Yosuke Kumekawa ◽  
Kazuhiro Kaneko ◽  
Hiroaki Ito ◽  
Toshinori Kurahashi ◽  
Kazuo Konishi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Late Toxicity ◽  
Complete Response ◽  
Definitive Chemoradiotherapy
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