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Poster session 01

641P - Phase I/II clinical and pharmacokinetic study of ecubectedin in combination with irinotecan in patients with selected advanced solid tumors

Date

14 Sep 2024

Session

Poster session 01

Topics

Cytotoxic Therapy

Tumour Site

Presenters

Ana Gil Torralvo

Citation

Annals of Oncology (2024) 35 (suppl_2): S482-S535. 10.1016/annonc/annonc1589

Authors

A. Gil Torralvo1, M. Vieito2, J. Martinez Perez1, G. Pretelli2, V. Martinez3, G.F. Boggio4, C.M. Fernandéz4, A. Hernandez4, E. Cristoveanu4, A. Belgrano4, C. Kahatt4, S. Fudio4, A. Nieto4, A. Redondo3

Author affiliations

  • 1 Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 2 Oncology, VHIO - Vall d'Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 3 Dept. Oncologia Medica, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 4 Clinical, PharmaMar S.A., 28770 - Colmenar Viejo/ES

Resources

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Abstract 641P

Background

Ecubectedin –PM14– (ECU) is a new chemical entity that forms DNA adducts that inhibit RNA synthesis and active transcription of protein-coding genes. Antitumor activity as single agent and combined with Irinotecan (IRI) has been shown in vitro and in vivo in mice bearing xenografted human-derived tumors.

Methods

Open-label, dose-escalating, phase 1/2 trial of ECU administered as a 3-hour infusion + IRI i.v. D1 q3wk in patients (pts) with selected advanced solid tumors, adequate organ function and ECOG PS score of 0-1. 1ry endpoint of phase 1 is to determine the maximum tolerated dose (MTD) and recommended dose (RD) of the combination, and of phase 2 is to confirm RD and evaluate efficacy (overall response rate, ORR) in selected tumor types.

Results

Phase 1: 30 pts were treated. Baseline characteristics: median age 60 years; female 70%; ECOG PS 0: 43%; median no. of prior lines (range): 4 (1-8). Most common tumor types: ovarian (n=7), NSCLC (n=5), STS (n=4). The MTD was ECU 4.5 mg/m2 + IRI 50 mg/m2 + 1ry GCSF prophylaxis D1 q3wk. The RD was ECU 4.5 mg/m2 + IRI 40 mg/m2 + 1ry GCSF prophylaxis D1 q3wk (dose-limiting toxicities [DLTs] at RD: G3 febrile neutropenia/ vomiting/ diarrhea in one pt, and G3 vomiting in another pt). Main treatment-related or unknown adverse events at the RD (n=15) were fatigue (80%), nausea (60%) and decreased appetite (33%). Main grade 3/4 lab abnormalities were transaminase increase (40%) and neutropenia (27%) -11 pts received 1ry GCSF prophylaxis-. Only one pt (7%) had febrile neutropenia (without 1ry GCSF prophylaxis). Antitumor activity comprised stable disease ≥4 months in 9 pts (30%) at all dose levels, mainly in NSCLC. Mean (CV%) plasma clearance of ECU was 4.9 L/h [56%]. PK parameters of IRI and SN-38 were similar to previously reported values. Phase 2 is ongoing, and only recruiting NSCLC patients. At cutoff, 9 pts have been treated. Safety and efficacy data of this cohort will be updated at the meeting.

Conclusions

At the RD, ECU + IRI + 1ry GCSF prophylaxis has a manageable safety profile. Hematological abnormalities, fatigue, transaminase increase and nausea were the main toxicities. No major PK drug-drug interactions between ECU and IRI were found.

Clinical trial identification

EudraCT 2021-000415-23.

Editorial acknowledgement

Legal entity responsible for the study

PharmaMar S.A.

Funding

PharmaMar S.A.

Disclosure

A. Gil Torralvo: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Daiichi Sankyo. M. Vieito: Financial Interests, Personal, Invited Speaker: Novocure; Financial Interests, Personal, Other, Steering committee member: BMS; Non-Financial Interests, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. G.F. Boggio, C. Kahatt, S. Fudio, A. Nieto: Financial Interests, Personal, Full or part-time Employment: PharmaMar; Financial Interests, Personal, Stocks/Shares: PharmaMar. C.M. Fernandéz, A. Hernandez, E. Cristoveanu: Financial Interests, Personal, Full or part-time Employment: PharmaMar. A. Redondo: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, GSK, PharmaMar, Pharma&; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, PharmaMar, Boehringer Ingelheim; Financial Interests, Institutional, Local PI: Roche, Eisai, PharmaMar. All other authors have declared no conflicts of interest.

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