Abstract 113P
Background
Our real-world data show high response rates with the COIB regimen for mCRC (Liu, Ou et al. 2022). But the appropriate dosage needs to be carefully explored. Therefore, we designed this prospective phase I/II study to determine the efficacy and tolerability of this combination regimen in the first-line treatment of mCRC.
Methods
This study consists of dose escalation (DES) and dose expansion (DEX). The primary objective in DES phase was to evaluate safety and tolerability of I combined with COB, followed by a DEX phase to verify the safety and tolerability profile of the combination therapy. Primary endpoints included recommended phase ll dose (RP2D) and efficacy of the combination. Other end points included exploratory biomarkers of drug activity. I was administered once a day (QD) at two dose levels (150mg/㎡ or 165mg/㎡) in combination with C (1g/㎡ bid, day 1-7)+ O (85mg/㎡, day 1)+B (5mg/kg, day 1), every 14 days (Q2W).
Results
As of August 13, 2023, 97 pts (median age: 58 years; 30% female; 77% left-sided intestine; 43 KRAS mutation, 6 NRAS mutation, 4 BRAF mutation, 31 wild type, 13 unknown) were treated (6 in DES, 91 in DEX). None of the 3 pts in irinotecan dose level 1 or 3 pts in irinotecan dose level 2 of DES had dose limiting toxicities (DLTs), and irinotecan (165mg/㎡, day1) was the RP2D. Treatment-related adverse events (TRAEs) of any grade occurred in 87 (89.7%) pts. TRAEs of grade ≥ 3 were mainly myelosuppression (20 pts, 20.6%) and diarrhea (10 pts, 10.3%). There were no fatal TRAEs. Of 90 pts evaluable for response, Objective response rate (ORR) was 73.3% (95% CI: 64.1%, 82.4%), Disease control rate (DCR) was 98.8% (95% CI: 96.7%, 100.0%).22 patients were successfully transformed and underwent radical resection, No evidence of disease (NED) rate was 22.7% (95% CI: 14.4%, 31.0%). With median follow-up of 17.0 months, 46 pts had progressive disease, median progression free survival (PFS) was 13.0 months(95%CI: 10.8, 19.3), overall survival (OS) are not yet mature. Detection biomarkers of drug activity is in progress.
Conclusions
The RP2D of irinotecan in COIB regimen is 165 mg/m2. The efficacy of the regimen is promising with well tolerance.
Clinical trial identification
NCT04380103.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Development Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MODP2022002).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
39P - Prognostic significance of hypoxic microenvironment biomarkers in invasive ductal breast cancer
Presenter: Sungmin Kang
Session: Poster Display
Resources:
Abstract
40P - Intra-tumoral CD3, CD4, and CD8 as prognostic biomarkers in Asian breast cancer
Presenter: Jia Wern Pan
Session: Poster Display
Resources:
Abstract
41P - Brown fat activation demonstrated on FDG PET/CT predicts survival outcome
Presenter: Sonya Park
Session: Poster Display
Resources:
Abstract
42P - A promising anticancer drug for triple-negative breast cancer: OZ-001 suppresses tumor growth by dual targeting STAT3 and calcium signaling
Presenter: Jisun Kim
Session: Poster Display
Resources:
Abstract
43P - Performance evaluation of a combined risk model for breast cancer risk prediction in Indonesian population (TRIP Study)
Presenter: Marco Wijaya
Session: Poster Display
Resources:
Abstract
44P - Pathological complete response to neoadjuvant chemotherapy and outcomes in Her-2 negative locally advanced breast cancer
Presenter: Amrith Patel
Session: Poster Display
Resources:
Abstract
45P - Demographic determinants of pathological complete response after neoadjuvant chemotherapy in breast cancer
Presenter: Anvesh Dharanikota
Session: Poster Display
Resources:
Abstract
46P - Predicting toxicity following cancer chemotherapy by detecting transporter gene ABCB1 (C1236T, G2677T/A, C3435CT) polymorphism in breast cancer patients receiving chemotherapy with anthracycline and taxane either sequentially or concomitantly
Presenter: Tanuma Mistry
Session: Poster Display
Resources:
Abstract
47P - Sequencing of chemotherapy and surgery among older triple-negative and HER2-positive breast cancer patients with comorbidities
Presenter: Anvesh Dharanikota
Session: Poster Display
Resources:
Abstract
48P - The impact of preoperative axillary ultrasound on the false negative rate of sentinel lymph node biopsy in post neoadjuvant chemotherapy breast cancer patients
Presenter: Byshetty Rajendar
Session: Poster Display
Resources:
Abstract