LBA27 Additional analyses of MOUNTAINEER: A phase II study of tucatinib and trastuzumab for HER2-positive mCRC

HER2 amplification/overexpression (HER2+) occurs in ∼3-5% of patients (pts) with metastatic colorectal cancer (mCRC). The primary analysis of MOUNTAINEER (NCT03043313) in cohorts A+B treated with tucatinib (TUC) + trastuzumab (Tras) was previously reported and showed tolerability and a confirmed objective response rate (cORR) per blinded independent central review (BICR) of 38.1%. Here, additional results of TUC monotherapy (cohort C) are reported. have been reported in a prior presentation (Strickler et al. ESMO-WCGI 2022 abstract no. LBA-2). Eligible pts had HER2+ (per local IHC, ISH, or NGS testing) RAS WT mCRC refractory to standard of care. Pts who initially received TUC monotherapy could cross over and receive TUC + Tras for radiographic progression or stable disease by 12 weeks. Prespecified analyses for cohort C include ORR by 12 weeks and disease control rate (DCR) by BICR; cORR by BICR for crossover pts, and safety for monotherapy and crossover pts. As of 28 Mar 2022, 86 pts received ≥1 dose of study treatment in cohorts A+B and 30 pts in cohort C. The ORR by week 12 in cohort C was 3.3% (95% CI, 0.1, 17.2) with DCR of 80.0%. Twenty-eight of 30 pts (93.0%) crossed over to received TUC + Tras, with cORR of 17.9% (95% CI, 6.1, 36.9). The most common AEs with TUC monotherapy were diarrhoea (33.3%), abdominal pain (20.0%), and fatigue (20.0%), which were grade (gr) 1 or 2; the most common gr ≥3 events were ALT/AST increase (6.7% for both). The most common AE for post-crossover pts was diarrhoea (35.7%) which was gr 1 or 2; the most common gr ≥3 events were ALT/AST increase (7.1% and 10.7%, respectively). There were no fatal AEs with TUC monotherapy or TUC + Tras. TUC monotherapy and TUC + Tras after crossover were well tolerated, consistent with the primary analysis. Disease stabilization was observed in most pts on TUC monotherapy; radiographic responses increased slightly after Tras addition. Monotherapy, crossover, and response data from the primary analysis show that concurrent initiation of dual HER2 blockade with TUC + Tras achieves optimal clinical benefit.