QL1203 vs placebo plus mFOLFOX6 as first-line therapy in RAS wild-type, metastatic colorectal cancer (mCRC): Interim analysis (IA) of a multicenter, randomized, double-blinded, parallel, phase 3 trial.

190 Background: Panitumumab plus FOLFOX or FOLFIRI has been approved as the first-line therapy for RAS wild-type mCRC. QL1203 is a panitumumab biosimilar showing similarity to the originator panitumumab (Vectibix, Amgen) in preclinical studies and phase 1 clinical pharmacokinetic study. Here we present results from interim analysis of a phase 3 trial (NCT04233151) investigating QL1203 vs placebo plus mFOLFOX6 as first-line therapy in Chinese patients (pts) with RAS wild-type mCRC. Methods: Pts with treatment-naïve, RAS and BRAF wild-type, mCRC unsuitable for radical resection and local therapy were enrolled and randomly assigned (2:1) to receive QL1203 (6 mg/kg) plus mFOLFOX6 once every 2 weeks (Q2W) or placebo plus mFOLFOX6 Q2W, stratified by primary tumor site, liver metastases, and previous neoadjuvant/adjuvant therapy. The primary endpoint was PFS assessed by a Blinded Independ Review Committee (BICR) per RECIST v1.1. Key secondary endpoints include PFS by investigator (INV), OS, ORR, DoR, and safety. This planned IA was conducted at 338 (81.25%) of 416 PFS events occurred. Results: From Jan 8, 2020 to Jun 12, 2023, 641 pts were randomized (QL1203/placebo, n=426/215). 551 (86.0%) pts had left-sided tumors (QL1203/placebo, 85.9%/86.0%). 433 (67.6%) pts had liver metastases (QL1203/placebo, 68.1%/66.5%). As of data cutoff of this IA (Mar 22, 2024), median follow-up was 23.8 months. Median PFS by BIRC was 11.20 months for QL1203 and 8.34 months for placebo (hazard ratio [HR], 0.61 [97.42% confidence interval [CI], 0.47-0.79]; stratified one-sided log-rank p<0.0001). Other efficacy results are presented (Table). Incidence of grade≥ 3 adverse events (AEs) related to study drug was 59.9% for QL1203 and 32.9% for placebo. The most common grade≥3 AE related to QL1203 was neutrophil count decreased (20.3%). Conclusions: QL1203 demonstrated significantly improved PFS versus placebo and higher ORR. Clinical trial information: NCT04233151 . QL1203 (n=426) Placebo (n=215) PFS by BIRC mPFS, months (95% CI) 11.20 (9.89-13.11) 8.34 (7.26-8.54) HR (97.42% CI) 0.61 (0.47-0.79) PFS by INV mPFS, months (95% CI) 10.91 (9.69-11.30) 8.41 (7.39-9.07) HR (95% CI) 0.74 (0.60-0.91) mOS, months (95% CI) 27.66 (24.74-32.79) 24.54 (20.17-27.79) HR (95% CI) 0.82 (0.64-1.06) ORR by BIRC, n (%) 68.31% 47.91% 95% CI 63.66-72.70 41.07-54.81 ORR by INV, n (%) 64.08% 49.30% 95% CI 59.33-68.65 42.44-56.19