Abstract 53P
Background
Capecitabine (cap) plus Bevacizumab (bev) is a standard option for previously untreated unresectable metastatic colorectal cancer (mCRC) patients (pts) deemed not fit for upfront chemotherapy doublets. A synergistic effect of the sequential administration of cap and Trifluridine/Tipiracil (FTD/TPI) has been shown both in vitro and in vivo models. Here, we present safety and preliminary activity results of the phase 1 TriComB study, an open-label, multicenter, phase 1/2 trial, evaluating FTD/TPI in combination with cap and bev in mCRC pts.
Methods
Patients with previously untreated mCRC, ineligible for oxaliplatin- and/or irinotecan- based regimens, were enrolled. A 3 + 3 dose escalation design was used to identify the recommended dose (RD) of FTD/TPI (days 15-19 and 22-26) in combination with cap (1000 mg/sqm/BID days 1-14) and bev (5 mg/kg day 1,15) in 28-days cycles. Adverse events (AEs) were reported according to CTCAE version 5.0 and tumor response was assessed by RECIST version 1.1.
Results
11 pts (5 men, 6 women; median age: 77, range: 47-84 years) were enrolled. For the first three patients (FTD/TPI: 25mg/sqm BID) no dose limiting toxicities (DLTs) were observed. At 30 mg/sqm BID dose level, 3/5 DLTs were reported: 2 pts experienced a dose delay of >7 days from the scheduled timing and 1 patient was unable to receive ≥ 75% of study drugs’ doses during the first cycle. FTD/TPI was de-escalated and 3 additional patients were treated at 25 mg/sqm BID. Since 1/6 pts experienced a DLT (grade 4 colonic perforation) that was identified as the RD. Grade 3/4 AEs are listed in the table. As of January 2024, Overall Response Rate is 72.7% (8/11 pts) and 66.7% (4/6 pts) in the overall population and at the RD, respectively. Table: 53P
Safety summary
| Events, n (%) | Overall population (N= 11) | FTD/TPI 25 mg/mq/bid (N= 6) |
| All grade ≥3 AEs | 8 (72.7) | 4 (66.7) |
| Neutropenia | 4 (36.4) | 0 |
| Diarrhea | 2 (18.2) | 1 (16.7) |
| Thromboembolic event | 1 (9.1) | 1 (16.7) |
| Fatigue | 1 (9.1) | 0 |
| AST/ALT increased | 1 (9.1) | 1 (16.7) |
| Hypokalemia | 1 (9.1) | 0 |
| Colonic perforation | 1 (9.1) | 1 (16.7) |
Conclusions
The sequential combination of cap and FTD/TPI with bev is feasible. The phase 2 of the study is ongoing to evaluate antitumor activity of this regimen in the same patients' population.
Clinical trial identification
NCT04564898.
Legal entity responsible for the study
GONO Foundation.
Funding
GONO Foundation, Servier.
Disclosure
G. Masi: Other, Advisory Role: AstraZeneca, Eisai, MSD Oncology, Roche; Other, Funding: Terumo. C. Cremolini: Financial Interests, Personal, Advisory Board: Roche, MSD, Pierre Fabre, Nordic Pharma, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Servier, Merck Serono; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Institutional, Invited Speaker: Roche, Bayer, Servier, Merck, Seagen, Hutchinson. All other authors have declared no conflicts of interest.