Abstract 1960
Background
The poor outcomes associated with current therapies for recurrent epithelial ovarian cancer (EOC) are thought to reflect the existence of drug-resistant ovarian cancer stem cells (OCSCs). TRX-E-002-1 is a novel, third generation benzopyran molecule that induces caspase-dependent and -independent apoptosis in CD44 positive ovarian cancer stem-like cells and CD44 negative ovarian somatic cancer cells. The dose escalation phase of a progressive design trial investigating intraperitoneal (IP)-administered TRX-E-002-1 monotherapy and in combination with standard of care for recurrent EOC (NCT02903771) has been completed with a Maximum Tolerated Dose (MTD) of 5 mg/kg established.
Methods
Women with platinum resistant, persistent or recurrent EOC were enrolled into the dose escalation phase of the study (Part A) in which TRX-E-002-1 monotherapy was administered IP weekly for 2 three-week cycles, after which combination with standard intravenous chemotherapy was allowed to a maximum of 8 cycles. Subjects were followed up for 3 months after the end of treatment. The study objectives were to establish the MTD and to evaluate safety, tolerability, pharmacokinetics and anti-tumour activity of TRX-E-002-1.
Results
A total of 9 subjects were evaluable for efficacy. Four of 9 patients completed 8 cycles (6 months); 2 remained progression-free at the 3-month endpoint post-treatment (9 months). Preliminary data on activity include 1 partial response (during combination treatment) and 5 patients with stable disease on monotherapy per RECIST criteria. The most common drug-related adverse events, not generally dose limiting, were abdominal pain (27%), fatigue (13%), vomiting (10%) and nausea (10%). There was limited accumulation of TRX-E-002-1 with multiple dosing across multiple concentration‐time points. PK profiles were comparable between all subjects with plasma concentrations progressively declining to < 10% maximal concentrations by 24 hours.
Conclusions
IP administered TRX-E-002-1 as a first-in-class, dual acting, anti-cancer therapy has demonstrated preliminary activity for the treatment of platinum resistant ovarian cancer.
Clinical trial identification
NCT02903771.
Editorial acknowledgement
Dr Caroline Markey, Markey Medical Consulting.
Legal entity responsible for the study
Kazia Therapeutics Limited.
Funding
Kazia Therapeutics Limited.
Disclosure
J. Coward: Honoraria (institution): Takeda Pharmaceuticals; Research grant / Funding (self): AstraZeneca; Leadership role, Overseas Trainee Sub-committee member: Royal Australasian College of Physicians. K. Moore: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Immunogen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Aravive; Advisory / Consultancy, Research grant / Funding (institution): OncoMed; Advisory / Consultancy: Samumed; Advisory / Consultancy: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: Cue; Research grant / Funding (self): Lilly; Research grant / Funding (self): PTC Therapeutics; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Agenus; Leadership role, Chair: NRG Oncology OVarian Committee; Leadership role, Associate Director: GOG Partners. D. Berg: Full / Part-time employment: Kazia Therapeutics Limited. J. Garner: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Kazia Therapeutics Limited. D. Dizon: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Kazia Therapeutics; Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self): Regeneron; Advisory / Consultancy: iMab. All other authors have declared no conflicts of interest.
Resources from the same session
3034 - Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL STUDY
Presenter: Maria Agnese Fabbri
Session: Poster Display session 2
Resources:
Abstract
4772 - Real world comparison of the impact of adjuvant capecitabine in women with high-risk triple-negative breast cancer after neoadjuvant chemotherapy
Presenter: Maysa Vilbert
Session: Poster Display session 2
Resources:
Abstract
5627 - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals
Presenter: Sabela Recalde
Session: Poster Display session 2
Resources:
Abstract
3917 - Impact of delayed neoadjuvant systemic chemotherapy on survival among breast cancer patients
Presenter: Mariana Chavez Mac Gregor
Session: Poster Display session 2
Resources:
Abstract
2246 - Clinical Confirmation of Higher Exposure to Niraparib in Tumor vs Plasma in Patients With Breast Cancer
Presenter: Laura Spring
Session: Poster Display session 2
Resources:
Abstract
581 - The rationale for the effectiveness of systemic treatment of breast cancer depending on the body weight index
Presenter: Mohammad Hojouj
Session: Poster Display session 2
Resources:
Abstract
5327 - Response to neoadjuvant chemotherapy in HER2 non-overexpressing breast cancer subtypes
Presenter: Silvia Mihaela Ilie
Session: Poster Display session 2
Resources:
Abstract
3613 - Pre-specified interim analysis of the SAFE trial (NCT2236806): a 4-arm randomized, double-blind, controlled study evaluating the efficacy and safety of cardiotoxicity prevention in non-metastatic breast cancer patients treated with anthracyclines with or without trastuzumab.
Presenter: Lorenzo Livi
Session: Poster Display session 2
Resources:
Abstract
3736 - Safety of hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-center comparative study.
Presenter: Icro Meattini
Session: Poster Display session 2
Resources:
Abstract
5085 - Usefulness of NT-ProBNP as a biomarker of cardiotoxicity in breast cancer patients treated with trastuzumab
Presenter: Isabel Blancas López-Barajas
Session: Poster Display session 2
Resources:
Abstract