Abstract 3811
Background
LUR is a new agent that exerts antitumor activity through inhibition of trans-activated transcription and modulation of tumor microenvironment. Preclinical synergism/additivity in combination with IRI has been reported, thus prompting the conduct of this trial.
Methods
Phase I trial to evaluate escalating doses of LUR on Day (D) 1 plus a fixed dose of IRI 75 mg/m2 on D1 and D8 every 3 weeks (q3w) in pts with advanced solid tumors, enrolled following a standard 3 + 3 dose escalation design.
Results
39 pts were treated at 5 dose levels (DL); 13 at the recommended dose (RD). 56% were females, 69% had ECOG PS = 1; median age was 58 years; median of 2 prior chemotherapy lines for advanced disease (range, 0 − 4) per pt. RD was defined as LUR 2.0 mg/m2 on D1 + IRI 75 mg/m2 on D1 and D8 q3w + GCSF. Dose-limiting toxicities in Cycle 1 were observed in 2/3 evaluable pts at the maximum tolerated dose (MTD) and in 3/13 evaluable pts at the RD. At the MTD and the RD, DLTs were skipping IRI D8 doses due to grade (G) 3-4 neutropenia (n = 3 patients) or G2-4 thrombocytopenia (n = 2). At the RD common G1/2 toxicities were nausea, vomiting, fatigue, diarrhea, anorexia and neuropathy; G3/4 hematological abnormalities comprised neutropenia (33%), but no thrombocytopenia. Objective RECIST responses were documented in 6/34 evaluable pts (18%): 3/11 pts with small cell lung cancer (SCLC), 2/2 pts with endometrial carcinoma (EC) and 1/3 pts with glioblastoma (GB). Most responses (5/12 evaluable patients [42%]) were at the RD. One pt with EC has an ongoing PR after 20 cycles. Prolonged SD > 4 months were observed in pancreatic carcinoma (3/6 pts), soft tissue sarcoma (STS) (5/9 pts) and SCLC (6/11, including 4 with SD for 6, 9, 11 and 26+ months).
Conclusions
The combination of LUR and IRI is well tolerated, with no unexpected toxicities. Myelosuppression was dose-limiting, but predictable and manageable. The RD is LUR 2.0 mg/m2 on D1 + IRI 75 mg/m2 on D1 and D8 q3w with GCSF. Notable antitumor activity was observed, especially in SCLC, EC, GB and STS. Expansion in these indications is warranted.
Clinical trial identification
NCT02611024.
Editorial acknowledgement
Legal entity responsible for the study
PharmaMar SA.
Funding
PharmaMar.
Disclosure
S. Ponce Aix: Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Roche, BMS, MSD. G. Coté: Advisory / Consultancy: Agios; Research grant / Funding (institution), Research funding to my institution for the conduct of clinical trials; no salary support: Epizyme, Eisai, Macrogenics, Boston Biomedical, Plexxicon, Merck KGaA/EMD Serono Research and Development Institute, CBA Inc, Bayer. R. Nuñez: Shareholder / Stockholder / Stock options, Full / Part-time employment: PharmaMar. M. Siguero: Shareholder / Stockholder / Stock options, Full / Part-time employment: PharmaMar. M. Insa: Full / Part-time employment: PharmaMar. M. Cullell-Young: Shareholder / Stockholder / Stock options, Full / Part-time employment: PharmaMar. C. Kahatt: Shareholder / Stockholder / Stock options, Full / Part-time employment: PharmaMar. A. Zeaiter: Shareholder / Stockholder / Stock options, Full / Part-time employment: PharmaMar. L. Paz-Ares: Advisory / Consultancy: Amgen; AstraZeneca; Boehringer Ingelheim; Bristol-Myers Squibb; Clovis Oncology; MSD; Novartis; Pfizer; Roche; Takeda. All other authors have declared no conflicts of interest.
Resources from the same session
5037 - CXCR4, CCR2 and CCR5 expression in subsets of tumor cells with stem and/or EMT features
Presenter: Olga Savelieva
Session: Poster Display session 1
Resources:
Abstract
5729 - Expression of mutant p53 affects cancer cell sensitivity to topotecan
Presenter: Rimma Mingaleeva
Session: Poster Display session 1
Resources:
Abstract
5725 - Breast cancer organoids a new tool for the prediction of drugs penetration and patient’outcome
Presenter: Giuseppina Roscigno
Session: Poster Display session 1
Resources:
Abstract
5680 - Aptamer-mediated exosomes detection for early breast cancer identification.
Presenter: Cristina Quintavalle
Session: Poster Display session 1
Resources:
Abstract
2460 - MicroRNA-181c promotes tamoxifen resistance in breast cancer cells via upregulation Akt/mTOR axis
Presenter: Alexander Scherbakov
Session: Poster Display session 1
Resources:
Abstract
3751 - Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Presenter: Sandhya Sreedharan
Session: Poster Display session 1
Resources:
Abstract
4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.
Presenter: Joao Pinto
Session: Poster Display session 1
Resources:
Abstract
4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program
Presenter: Ana Monteiro
Session: Poster Display session 1
Resources:
Abstract
5340 - Quantitative imaging and characterization of collagen patterns in high grade serous ovarian carcinoma (HGSOC)
Presenter: Ruby Huang
Session: Poster Display session 1
Resources:
Abstract
4209 - Semiquantitative assessment of vimentin expression in prostate cancer (PC)
Presenter: Marina Puchinskaya
Session: Poster Display session 1
Resources:
Abstract