162TiP - Phase II study of consolidation treatment with holmium-166 (166Ho) TARE followed by maintenance systemic therapy (MT) in unresectable liver-limited (ULL) colorectal cancer (CRC) patients (pts) after standard first-line induction therapy: The HAITI trial

Background

Fluoropyrimidine plus target agents (TA) is a standard MT in ULL-CRC pts at best response after first-line therapy. The efficacy of ⁹⁰Y-TARE plus first-line chemotherapy in mCRC pts, has been investigated in randomized studies, highlighting improvement in time-to-liver progression, but failing to demonstrate advantage in overall survival (OS). In the phase III EPOCH trial, ⁹⁰Y-TARE increased progression-free survival (PFS) when added to second-line chemotherapy. Phase I-II studies reported promising results of ¹⁶⁶Ho-TARE in pts with refractory liver tumors including mCRC. We designed a phase II single-arm trial with ¹⁶⁶Ho-TARE as “consolidation” treatment followed by MT with fluoropyrimidine and TA in LL-CRC pts deemed unresectable both baseline and after first-line chemotherapy plus TA by a MDT evaluation.

Trial design

The HAITI study is a phase II trial of ¹⁶⁶Ho-TARE followed by MT in ULL-CRC pts, achieving partial response or stable disease after 6-12 cycles of first-line therapy. ULL-CRC pts who received first-line chemotherapy plus antiEGFR or plus bevacizumab, will be included in 2 cohorts: left sided RAS/BRAF wild-type (cohort A), right-sided and/or RAS mutated tumors (cohort B). Eligible pts will receive ¹⁶⁶Ho-TARE followed by MT until disease progression (PD), according to the respective cohort (fluopyrimidine plus antiEGFR in cohort A and fluoropyrimidine plus bevacizumab in cohort B). In case of bilobar disease, ¹⁶⁶Ho-TARE will be administered in 2 different procedures, one for each lobe. Primary endpoint is PFS rate at 9 and 8 months for cohort A and B, respectively, defined as the time from study enrollment to PD or death. Secondary endpoints are safety profile, PFS, OS and QoL. According to single arm single stage design, selecting p0=0.50, and p1=0.75, considering 80% power with α error of 0.05 (one-sided), a total of 23 pts should be enrolled in each cohort. The treatment will be judged promising if at least 16 pts will not experience PD at 9 and 8 months from the time of study inclusion in cohort A and B, respectively. The trial is ongoing in 8 Italian Oncology Units.

Clinical trial identification

NCT06332079.

Legal entity responsible for the study

GONO Foundation.

Funding

GONO Foundation, Terumo Europe.

Disclosure

B. Borelli: Financial Interests, Institutional, Invited Speaker: Terumo Europe; Financial Interests, Institutional, Funding: Terumo Europe. I. Bargellini: Financial Interests, Personal and Institutional, Other, Consultant: Terumo Europe. G. Boni: Financial Interests, Personal and Institutional, Invited Speaker: Terumo Europe. F. Pietrantonio: Financial Interests, Personal, Advisory Board: Amgen, Merck Serono, MSD, Bayer, Astellas, Takeda, GSK, Johnson&Johnson, Rottapharm; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, BMS, Lilly, Servier, Bayer, Pierre Fabre, AstraZeneca, Astellas, Daiichi Sankyo, Takeda; Financial Interests, Personal, Expert Testimony: Ipsen; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Incyte, Agenus; Financial Interests, Institutional, Invited Speaker: Lilly, Amgen. L. Antonuzzo: Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca, Roche, Astellas, Novartis, MSD, BMS, Ipsen, Merck Serono, Amgen, Bayer; Financial Interests, Personal, Other, Support for attending meeting and/or travel grant: AstraZeneca, Novartis, Ipsen, Merck Serono; Financial Interests, Institutional, Funding: Novartis, AstraZeneca. S. Tamberi: Financial Interests, Personal, Advisory Board: Gilead, AstraZeneca. A. Sartore Bianchi: Financial Interests, Personal and Institutional, Advisory Board: Amgen, Bayer, Novartis, Pierre Fabre, Servier and Takeda. 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. L. Crocetti: Financial Interests, Personal and Institutional, Invited Speaker: Terumo Europe. G. Masi: Financial Interests, Personal and Institutional, Invited Speaker: Terumo Europe, Sirtex; Financial Interests, Institutional, Funding: Terumo Europe. All other authors have declared no conflicts of interest.